Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro
Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, inc...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Steven P. Maher [verfasserIn] Amélie Vantaux [verfasserIn] Victor Chaumeau [verfasserIn] Adeline C. Y. Chua [verfasserIn] Caitlin A. Cooper [verfasserIn] Chiara Andolina [verfasserIn] Julie Péneau [verfasserIn] Mélanie Rouillier [verfasserIn] Zaira Rizopoulos [verfasserIn] Sivchheng Phal [verfasserIn] Eakpor Piv [verfasserIn] Chantrea Vong [verfasserIn] Sreyvouch Phen [verfasserIn] Chansophea Chhin [verfasserIn] Baura Tat [verfasserIn] Sivkeng Ouk [verfasserIn] Bros Doeurk [verfasserIn] Saorin Kim [verfasserIn] Sangrawee Suriyakan [verfasserIn] Praphan Kittiphanakun [verfasserIn] Nana Akua Awuku [verfasserIn] Amy J. Conway [verfasserIn] Rays H. Y. Jiang [verfasserIn] Bruce Russell [verfasserIn] Pablo Bifani [verfasserIn] Brice Campo [verfasserIn] François Nosten [verfasserIn] Benoît Witkowski [verfasserIn] Dennis E. Kyle [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2021 |
|---|
| Übergeordnetes Werk: |
In: Scientific Reports - Nature Portfolio, 2011, 11(2021), 1, Seite 18 |
|---|---|
| Übergeordnetes Werk: |
volume:11 ; year:2021 ; number:1 ; pages:18 |
| Links: |
|---|
| DOI / URN: |
10.1038/s41598-021-99152-9 |
|---|
| Katalog-ID: |
DOAJ008984492 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ008984492 | ||
| 003 | DE-627 | ||
| 005 | 20230310014323.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41598-021-99152-9 |2 doi | |
| 035 | |a (DE-627)DOAJ008984492 | ||
| 035 | |a (DE-599)DOAJ82bd81cce09f483dac02985c053a9b50 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 0 | |a Steven P. Maher |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. | ||
| 653 | 0 | |a Medicine | |
| 653 | 0 | |a R | |
| 653 | 0 | |a Science | |
| 653 | 0 | |a Q | |
| 700 | 0 | |a Amélie Vantaux |e verfasserin |4 aut | |
| 700 | 0 | |a Victor Chaumeau |e verfasserin |4 aut | |
| 700 | 0 | |a Adeline C. Y. Chua |e verfasserin |4 aut | |
| 700 | 0 | |a Caitlin A. Cooper |e verfasserin |4 aut | |
| 700 | 0 | |a Chiara Andolina |e verfasserin |4 aut | |
| 700 | 0 | |a Julie Péneau |e verfasserin |4 aut | |
| 700 | 0 | |a Mélanie Rouillier |e verfasserin |4 aut | |
| 700 | 0 | |a Zaira Rizopoulos |e verfasserin |4 aut | |
| 700 | 0 | |a Sivchheng Phal |e verfasserin |4 aut | |
| 700 | 0 | |a Eakpor Piv |e verfasserin |4 aut | |
| 700 | 0 | |a Chantrea Vong |e verfasserin |4 aut | |
| 700 | 0 | |a Sreyvouch Phen |e verfasserin |4 aut | |
| 700 | 0 | |a Chansophea Chhin |e verfasserin |4 aut | |
| 700 | 0 | |a Baura Tat |e verfasserin |4 aut | |
| 700 | 0 | |a Sivkeng Ouk |e verfasserin |4 aut | |
| 700 | 0 | |a Bros Doeurk |e verfasserin |4 aut | |
| 700 | 0 | |a Saorin Kim |e verfasserin |4 aut | |
| 700 | 0 | |a Sangrawee Suriyakan |e verfasserin |4 aut | |
| 700 | 0 | |a Praphan Kittiphanakun |e verfasserin |4 aut | |
| 700 | 0 | |a Nana Akua Awuku |e verfasserin |4 aut | |
| 700 | 0 | |a Amy J. Conway |e verfasserin |4 aut | |
| 700 | 0 | |a Rays H. Y. Jiang |e verfasserin |4 aut | |
| 700 | 0 | |a Bruce Russell |e verfasserin |4 aut | |
| 700 | 0 | |a Pablo Bifani |e verfasserin |4 aut | |
| 700 | 0 | |a Brice Campo |e verfasserin |4 aut | |
| 700 | 0 | |a François Nosten |e verfasserin |4 aut | |
| 700 | 0 | |a Benoît Witkowski |e verfasserin |4 aut | |
| 700 | 0 | |a Dennis E. Kyle |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Scientific Reports |d Nature Portfolio, 2011 |g 11(2021), 1, Seite 18 |w (DE-627)663366712 |w (DE-600)2615211-3 |x 20452322 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2021 |g number:1 |g pages:18 |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41598-021-99152-9 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/82bd81cce09f483dac02985c053a9b50 |z kostenfrei |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41598-021-99152-9 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2045-2322 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 912 | |a GBV_ILN_11 | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_31 | ||
| 912 | |a GBV_ILN_39 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_70 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_170 | ||
| 912 | |a GBV_ILN_171 | ||
| 912 | |a GBV_ILN_206 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_370 | ||
| 912 | |a GBV_ILN_381 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_2005 | ||
| 912 | |a GBV_ILN_2009 | ||
| 912 | |a GBV_ILN_2011 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_2055 | ||
| 912 | |a GBV_ILN_2111 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4335 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4700 | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2021 |e 1 |h 18 | ||
| author_variant |
s p m spm a v av v c vc a c y c acyc c a c cac c a ca j p jp m r mr z r zr s p sp e p ep c v cv s p sp c c cc b t bt s o so b d bd s k sk s s ss p k pk n a a naa a j c ajc r h y j rhyj b r br p b pb b c bc f n fn b w bw d e k dek |
|---|---|
| matchkey_str |
article:20452322:2021----::rbnteitnthmsniiiyflsoimialvrtgprstsndmntainfaiou |
| hierarchy_sort_str |
2021 |
| publishDate |
2021 |
| allfields |
10.1038/s41598-021-99152-9 doi (DE-627)DOAJ008984492 (DE-599)DOAJ82bd81cce09f483dac02985c053a9b50 DE-627 ger DE-627 rakwb eng Steven P. Maher verfasserin aut Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. Medicine R Science Q Amélie Vantaux verfasserin aut Victor Chaumeau verfasserin aut Adeline C. Y. Chua verfasserin aut Caitlin A. Cooper verfasserin aut Chiara Andolina verfasserin aut Julie Péneau verfasserin aut Mélanie Rouillier verfasserin aut Zaira Rizopoulos verfasserin aut Sivchheng Phal verfasserin aut Eakpor Piv verfasserin aut Chantrea Vong verfasserin aut Sreyvouch Phen verfasserin aut Chansophea Chhin verfasserin aut Baura Tat verfasserin aut Sivkeng Ouk verfasserin aut Bros Doeurk verfasserin aut Saorin Kim verfasserin aut Sangrawee Suriyakan verfasserin aut Praphan Kittiphanakun verfasserin aut Nana Akua Awuku verfasserin aut Amy J. Conway verfasserin aut Rays H. Y. Jiang verfasserin aut Bruce Russell verfasserin aut Pablo Bifani verfasserin aut Brice Campo verfasserin aut François Nosten verfasserin aut Benoît Witkowski verfasserin aut Dennis E. Kyle verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 18 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:18 https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/article/82bd81cce09f483dac02985c053a9b50 kostenfrei https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 18 |
| spelling |
10.1038/s41598-021-99152-9 doi (DE-627)DOAJ008984492 (DE-599)DOAJ82bd81cce09f483dac02985c053a9b50 DE-627 ger DE-627 rakwb eng Steven P. Maher verfasserin aut Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. Medicine R Science Q Amélie Vantaux verfasserin aut Victor Chaumeau verfasserin aut Adeline C. Y. Chua verfasserin aut Caitlin A. Cooper verfasserin aut Chiara Andolina verfasserin aut Julie Péneau verfasserin aut Mélanie Rouillier verfasserin aut Zaira Rizopoulos verfasserin aut Sivchheng Phal verfasserin aut Eakpor Piv verfasserin aut Chantrea Vong verfasserin aut Sreyvouch Phen verfasserin aut Chansophea Chhin verfasserin aut Baura Tat verfasserin aut Sivkeng Ouk verfasserin aut Bros Doeurk verfasserin aut Saorin Kim verfasserin aut Sangrawee Suriyakan verfasserin aut Praphan Kittiphanakun verfasserin aut Nana Akua Awuku verfasserin aut Amy J. Conway verfasserin aut Rays H. Y. Jiang verfasserin aut Bruce Russell verfasserin aut Pablo Bifani verfasserin aut Brice Campo verfasserin aut François Nosten verfasserin aut Benoît Witkowski verfasserin aut Dennis E. Kyle verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 18 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:18 https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/article/82bd81cce09f483dac02985c053a9b50 kostenfrei https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 18 |
| allfields_unstemmed |
10.1038/s41598-021-99152-9 doi (DE-627)DOAJ008984492 (DE-599)DOAJ82bd81cce09f483dac02985c053a9b50 DE-627 ger DE-627 rakwb eng Steven P. Maher verfasserin aut Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. Medicine R Science Q Amélie Vantaux verfasserin aut Victor Chaumeau verfasserin aut Adeline C. Y. Chua verfasserin aut Caitlin A. Cooper verfasserin aut Chiara Andolina verfasserin aut Julie Péneau verfasserin aut Mélanie Rouillier verfasserin aut Zaira Rizopoulos verfasserin aut Sivchheng Phal verfasserin aut Eakpor Piv verfasserin aut Chantrea Vong verfasserin aut Sreyvouch Phen verfasserin aut Chansophea Chhin verfasserin aut Baura Tat verfasserin aut Sivkeng Ouk verfasserin aut Bros Doeurk verfasserin aut Saorin Kim verfasserin aut Sangrawee Suriyakan verfasserin aut Praphan Kittiphanakun verfasserin aut Nana Akua Awuku verfasserin aut Amy J. Conway verfasserin aut Rays H. Y. Jiang verfasserin aut Bruce Russell verfasserin aut Pablo Bifani verfasserin aut Brice Campo verfasserin aut François Nosten verfasserin aut Benoît Witkowski verfasserin aut Dennis E. Kyle verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 18 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:18 https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/article/82bd81cce09f483dac02985c053a9b50 kostenfrei https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 18 |
| allfieldsGer |
10.1038/s41598-021-99152-9 doi (DE-627)DOAJ008984492 (DE-599)DOAJ82bd81cce09f483dac02985c053a9b50 DE-627 ger DE-627 rakwb eng Steven P. Maher verfasserin aut Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. Medicine R Science Q Amélie Vantaux verfasserin aut Victor Chaumeau verfasserin aut Adeline C. Y. Chua verfasserin aut Caitlin A. Cooper verfasserin aut Chiara Andolina verfasserin aut Julie Péneau verfasserin aut Mélanie Rouillier verfasserin aut Zaira Rizopoulos verfasserin aut Sivchheng Phal verfasserin aut Eakpor Piv verfasserin aut Chantrea Vong verfasserin aut Sreyvouch Phen verfasserin aut Chansophea Chhin verfasserin aut Baura Tat verfasserin aut Sivkeng Ouk verfasserin aut Bros Doeurk verfasserin aut Saorin Kim verfasserin aut Sangrawee Suriyakan verfasserin aut Praphan Kittiphanakun verfasserin aut Nana Akua Awuku verfasserin aut Amy J. Conway verfasserin aut Rays H. Y. Jiang verfasserin aut Bruce Russell verfasserin aut Pablo Bifani verfasserin aut Brice Campo verfasserin aut François Nosten verfasserin aut Benoît Witkowski verfasserin aut Dennis E. Kyle verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 18 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:18 https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/article/82bd81cce09f483dac02985c053a9b50 kostenfrei https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 18 |
| allfieldsSound |
10.1038/s41598-021-99152-9 doi (DE-627)DOAJ008984492 (DE-599)DOAJ82bd81cce09f483dac02985c053a9b50 DE-627 ger DE-627 rakwb eng Steven P. Maher verfasserin aut Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. Medicine R Science Q Amélie Vantaux verfasserin aut Victor Chaumeau verfasserin aut Adeline C. Y. Chua verfasserin aut Caitlin A. Cooper verfasserin aut Chiara Andolina verfasserin aut Julie Péneau verfasserin aut Mélanie Rouillier verfasserin aut Zaira Rizopoulos verfasserin aut Sivchheng Phal verfasserin aut Eakpor Piv verfasserin aut Chantrea Vong verfasserin aut Sreyvouch Phen verfasserin aut Chansophea Chhin verfasserin aut Baura Tat verfasserin aut Sivkeng Ouk verfasserin aut Bros Doeurk verfasserin aut Saorin Kim verfasserin aut Sangrawee Suriyakan verfasserin aut Praphan Kittiphanakun verfasserin aut Nana Akua Awuku verfasserin aut Amy J. Conway verfasserin aut Rays H. Y. Jiang verfasserin aut Bruce Russell verfasserin aut Pablo Bifani verfasserin aut Brice Campo verfasserin aut François Nosten verfasserin aut Benoît Witkowski verfasserin aut Dennis E. Kyle verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 18 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:18 https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/article/82bd81cce09f483dac02985c053a9b50 kostenfrei https://doi.org/10.1038/s41598-021-99152-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 18 |
| language |
English |
| source |
In Scientific Reports 11(2021), 1, Seite 18 volume:11 year:2021 number:1 pages:18 |
| sourceStr |
In Scientific Reports 11(2021), 1, Seite 18 volume:11 year:2021 number:1 pages:18 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Medicine R Science Q |
| isfreeaccess_bool |
true |
| container_title |
Scientific Reports |
| authorswithroles_txt_mv |
Steven P. Maher @@aut@@ Amélie Vantaux @@aut@@ Victor Chaumeau @@aut@@ Adeline C. Y. Chua @@aut@@ Caitlin A. Cooper @@aut@@ Chiara Andolina @@aut@@ Julie Péneau @@aut@@ Mélanie Rouillier @@aut@@ Zaira Rizopoulos @@aut@@ Sivchheng Phal @@aut@@ Eakpor Piv @@aut@@ Chantrea Vong @@aut@@ Sreyvouch Phen @@aut@@ Chansophea Chhin @@aut@@ Baura Tat @@aut@@ Sivkeng Ouk @@aut@@ Bros Doeurk @@aut@@ Saorin Kim @@aut@@ Sangrawee Suriyakan @@aut@@ Praphan Kittiphanakun @@aut@@ Nana Akua Awuku @@aut@@ Amy J. Conway @@aut@@ Rays H. Y. Jiang @@aut@@ Bruce Russell @@aut@@ Pablo Bifani @@aut@@ Brice Campo @@aut@@ François Nosten @@aut@@ Benoît Witkowski @@aut@@ Dennis E. Kyle @@aut@@ |
| publishDateDaySort_date |
2021-01-01T00:00:00Z |
| hierarchy_top_id |
663366712 |
| id |
DOAJ008984492 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ008984492</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230310014323.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230225s2021 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/s41598-021-99152-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ008984492</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ82bd81cce09f483dac02985c053a9b50</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Steven P. Maher</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Science</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Q</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amélie Vantaux</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Victor Chaumeau</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adeline C. Y. Chua</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Caitlin A. Cooper</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chiara Andolina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Julie Péneau</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mélanie Rouillier</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zaira Rizopoulos</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sivchheng Phal</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Eakpor Piv</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chantrea Vong</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sreyvouch Phen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chansophea Chhin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Baura Tat</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sivkeng Ouk</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bros Doeurk</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Saorin Kim</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sangrawee Suriyakan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Praphan Kittiphanakun</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nana Akua Awuku</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amy J. Conway</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rays H. Y. Jiang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bruce Russell</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pablo Bifani</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Brice Campo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">François Nosten</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Benoît Witkowski</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Dennis E. Kyle</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Scientific Reports</subfield><subfield code="d">Nature Portfolio, 2011</subfield><subfield code="g">11(2021), 1, Seite 18</subfield><subfield code="w">(DE-627)663366712</subfield><subfield code="w">(DE-600)2615211-3</subfield><subfield code="x">20452322</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:11</subfield><subfield code="g">year:2021</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:18</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41598-021-99152-9</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/82bd81cce09f483dac02985c053a9b50</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41598-021-99152-9</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2045-2322</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_171</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_381</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4335</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">11</subfield><subfield code="j">2021</subfield><subfield code="e">1</subfield><subfield code="h">18</subfield></datafield></record></collection>
|
| author |
Steven P. Maher |
| spellingShingle |
Steven P. Maher misc Medicine misc R misc Science misc Q Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro |
| authorStr |
Steven P. Maher |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)663366712 |
| format |
electronic Article |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
| collection |
DOAJ |
| remote_str |
true |
| illustrated |
Not Illustrated |
| issn |
20452322 |
| topic_title |
Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro |
| topic |
misc Medicine misc R misc Science misc Q |
| topic_unstemmed |
misc Medicine misc R misc Science misc Q |
| topic_browse |
misc Medicine misc R misc Science misc Q |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
cr |
| hierarchy_parent_title |
Scientific Reports |
| hierarchy_parent_id |
663366712 |
| hierarchy_top_title |
Scientific Reports |
| isfreeaccess_txt |
true |
| familylinks_str_mv |
(DE-627)663366712 (DE-600)2615211-3 |
| title |
Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro |
| ctrlnum |
(DE-627)DOAJ008984492 (DE-599)DOAJ82bd81cce09f483dac02985c053a9b50 |
| title_full |
Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro |
| author_sort |
Steven P. Maher |
| journal |
Scientific Reports |
| journalStr |
Scientific Reports |
| lang_code |
eng |
| isOA_bool |
true |
| recordtype |
marc |
| publishDateSort |
2021 |
| contenttype_str_mv |
txt |
| container_start_page |
18 |
| author_browse |
Steven P. Maher Amélie Vantaux Victor Chaumeau Adeline C. Y. Chua Caitlin A. Cooper Chiara Andolina Julie Péneau Mélanie Rouillier Zaira Rizopoulos Sivchheng Phal Eakpor Piv Chantrea Vong Sreyvouch Phen Chansophea Chhin Baura Tat Sivkeng Ouk Bros Doeurk Saorin Kim Sangrawee Suriyakan Praphan Kittiphanakun Nana Akua Awuku Amy J. Conway Rays H. Y. Jiang Bruce Russell Pablo Bifani Brice Campo François Nosten Benoît Witkowski Dennis E. Kyle |
| container_volume |
11 |
| format_se |
Elektronische Aufsätze |
| author-letter |
Steven P. Maher |
| doi_str_mv |
10.1038/s41598-021-99152-9 |
| author2-role |
verfasserin |
| title_sort |
probing the distinct chemosensitivity of plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro |
| title_auth |
Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro |
| abstract |
Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. |
| abstractGer |
Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. |
| abstract_unstemmed |
Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
| container_issue |
1 |
| title_short |
Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro |
| url |
https://doi.org/10.1038/s41598-021-99152-9 https://doaj.org/article/82bd81cce09f483dac02985c053a9b50 https://doaj.org/toc/2045-2322 |
| remote_bool |
true |
| author2 |
Amélie Vantaux Victor Chaumeau Adeline C. Y. Chua Caitlin A. Cooper Chiara Andolina Julie Péneau Mélanie Rouillier Zaira Rizopoulos Sivchheng Phal Eakpor Piv Chantrea Vong Sreyvouch Phen Chansophea Chhin Baura Tat Sivkeng Ouk Bros Doeurk Saorin Kim Sangrawee Suriyakan Praphan Kittiphanakun Nana Akua Awuku Amy J. Conway Rays H. Y. Jiang Bruce Russell Pablo Bifani Brice Campo François Nosten Benoît Witkowski Dennis E. Kyle |
| author2Str |
Amélie Vantaux Victor Chaumeau Adeline C. Y. Chua Caitlin A. Cooper Chiara Andolina Julie Péneau Mélanie Rouillier Zaira Rizopoulos Sivchheng Phal Eakpor Piv Chantrea Vong Sreyvouch Phen Chansophea Chhin Baura Tat Sivkeng Ouk Bros Doeurk Saorin Kim Sangrawee Suriyakan Praphan Kittiphanakun Nana Akua Awuku Amy J. Conway Rays H. Y. Jiang Bruce Russell Pablo Bifani Brice Campo François Nosten Benoît Witkowski Dennis E. Kyle |
| ppnlink |
663366712 |
| mediatype_str_mv |
c |
| isOA_txt |
true |
| hochschulschrift_bool |
false |
| doi_str |
10.1038/s41598-021-99152-9 |
| up_date |
2024-07-03T21:18:42.475Z |
| _version_ |
1803594259471794176 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ008984492</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230310014323.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230225s2021 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/s41598-021-99152-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ008984492</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ82bd81cce09f483dac02985c053a9b50</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Steven P. Maher</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Science</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Q</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amélie Vantaux</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Victor Chaumeau</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adeline C. Y. Chua</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Caitlin A. Cooper</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chiara Andolina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Julie Péneau</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mélanie Rouillier</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zaira Rizopoulos</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sivchheng Phal</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Eakpor Piv</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chantrea Vong</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sreyvouch Phen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chansophea Chhin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Baura Tat</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sivkeng Ouk</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bros Doeurk</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Saorin Kim</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sangrawee Suriyakan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Praphan Kittiphanakun</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nana Akua Awuku</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amy J. Conway</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rays H. Y. Jiang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bruce Russell</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pablo Bifani</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Brice Campo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">François Nosten</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Benoît Witkowski</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Dennis E. Kyle</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Scientific Reports</subfield><subfield code="d">Nature Portfolio, 2011</subfield><subfield code="g">11(2021), 1, Seite 18</subfield><subfield code="w">(DE-627)663366712</subfield><subfield code="w">(DE-600)2615211-3</subfield><subfield code="x">20452322</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:11</subfield><subfield code="g">year:2021</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:18</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41598-021-99152-9</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/82bd81cce09f483dac02985c053a9b50</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41598-021-99152-9</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2045-2322</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_171</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_381</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4335</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">11</subfield><subfield code="j">2021</subfield><subfield code="e">1</subfield><subfield code="h">18</subfield></datafield></record></collection>
|
| score |
7.400154 |