Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors

The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due t...
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Autor*in:	Ping Li [verfasserIn] Ruikun Du [verfasserIn] Yanyan Wang [verfasserIn] Xuewen Hou [verfasserIn] Lin Wang [verfasserIn] Xiujuan Zhao [verfasserIn] Peng Zhan [verfasserIn] Xinyong Liu [verfasserIn] Lijun Rong [verfasserIn] Qinghua Cui [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	influenza A virus chebulinic acid chebulagic acid neuraminidase neuraminidase inhibitor

Übergeordnetes Werk:	In: Frontiers in Microbiology - Frontiers Media S.A., 2011, 11(2020)
Übergeordnetes Werk:	volume:11 ; year:2020

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fmicb.2020.00182

Katalog-ID:	DOAJ003419878

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520			\|a The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs.
650		4	\|a influenza A virus
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951			\|a AR
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allfields	10.3389/fmicb.2020.00182 doi (DE-627)DOAJ003419878 (DE-599)DOAJ2784424ec4654f25bf0e2353aa8745cb DE-627 ger DE-627 rakwb eng QR1-502 Ping Li verfasserin aut Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs. influenza A virus chebulinic acid chebulagic acid neuraminidase neuraminidase inhibitor Microbiology Ruikun Du verfasserin aut Ruikun Du verfasserin aut Ruikun Du verfasserin aut Yanyan Wang verfasserin aut Xuewen Hou verfasserin aut Lin Wang verfasserin aut Xiujuan Zhao verfasserin aut Peng Zhan verfasserin aut Xinyong Liu verfasserin aut Lijun Rong verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.00182 kostenfrei https://doaj.org/article/2784424ec4654f25bf0e2353aa8745cb kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.00182/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
spelling	10.3389/fmicb.2020.00182 doi (DE-627)DOAJ003419878 (DE-599)DOAJ2784424ec4654f25bf0e2353aa8745cb DE-627 ger DE-627 rakwb eng QR1-502 Ping Li verfasserin aut Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs. influenza A virus chebulinic acid chebulagic acid neuraminidase neuraminidase inhibitor Microbiology Ruikun Du verfasserin aut Ruikun Du verfasserin aut Ruikun Du verfasserin aut Yanyan Wang verfasserin aut Xuewen Hou verfasserin aut Lin Wang verfasserin aut Xiujuan Zhao verfasserin aut Peng Zhan verfasserin aut Xinyong Liu verfasserin aut Lijun Rong verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.00182 kostenfrei https://doaj.org/article/2784424ec4654f25bf0e2353aa8745cb kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.00182/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfields_unstemmed	10.3389/fmicb.2020.00182 doi (DE-627)DOAJ003419878 (DE-599)DOAJ2784424ec4654f25bf0e2353aa8745cb DE-627 ger DE-627 rakwb eng QR1-502 Ping Li verfasserin aut Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs. influenza A virus chebulinic acid chebulagic acid neuraminidase neuraminidase inhibitor Microbiology Ruikun Du verfasserin aut Ruikun Du verfasserin aut Ruikun Du verfasserin aut Yanyan Wang verfasserin aut Xuewen Hou verfasserin aut Lin Wang verfasserin aut Xiujuan Zhao verfasserin aut Peng Zhan verfasserin aut Xinyong Liu verfasserin aut Lijun Rong verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.00182 kostenfrei https://doaj.org/article/2784424ec4654f25bf0e2353aa8745cb kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.00182/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfieldsGer	10.3389/fmicb.2020.00182 doi (DE-627)DOAJ003419878 (DE-599)DOAJ2784424ec4654f25bf0e2353aa8745cb DE-627 ger DE-627 rakwb eng QR1-502 Ping Li verfasserin aut Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs. influenza A virus chebulinic acid chebulagic acid neuraminidase neuraminidase inhibitor Microbiology Ruikun Du verfasserin aut Ruikun Du verfasserin aut Ruikun Du verfasserin aut Yanyan Wang verfasserin aut Xuewen Hou verfasserin aut Lin Wang verfasserin aut Xiujuan Zhao verfasserin aut Peng Zhan verfasserin aut Xinyong Liu verfasserin aut Lijun Rong verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.00182 kostenfrei https://doaj.org/article/2784424ec4654f25bf0e2353aa8745cb kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.00182/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfieldsSound	10.3389/fmicb.2020.00182 doi (DE-627)DOAJ003419878 (DE-599)DOAJ2784424ec4654f25bf0e2353aa8745cb DE-627 ger DE-627 rakwb eng QR1-502 Ping Li verfasserin aut Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs. influenza A virus chebulinic acid chebulagic acid neuraminidase neuraminidase inhibitor Microbiology Ruikun Du verfasserin aut Ruikun Du verfasserin aut Ruikun Du verfasserin aut Yanyan Wang verfasserin aut Xuewen Hou verfasserin aut Lin Wang verfasserin aut Xiujuan Zhao verfasserin aut Peng Zhan verfasserin aut Xinyong Liu verfasserin aut Lijun Rong verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut Qinghua Cui verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 11(2020) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:11 year:2020 https://doi.org/10.3389/fmicb.2020.00182 kostenfrei https://doaj.org/article/2784424ec4654f25bf0e2353aa8745cb kostenfrei https://www.frontiersin.org/article/10.3389/fmicb.2020.00182/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
language	English
source	In Frontiers in Microbiology 11(2020) volume:11 year:2020
sourceStr	In Frontiers in Microbiology 11(2020) volume:11 year:2020
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topic_facet	influenza A virus chebulinic acid chebulagic acid neuraminidase neuraminidase inhibitor Microbiology
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container_title	Frontiers in Microbiology
authorswithroles_txt_mv	Ping Li @@aut@@ Ruikun Du @@aut@@ Yanyan Wang @@aut@@ Xuewen Hou @@aut@@ Lin Wang @@aut@@ Xiujuan Zhao @@aut@@ Peng Zhan @@aut@@ Xinyong Liu @@aut@@ Lijun Rong @@aut@@ Qinghua Cui @@aut@@
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callnumber-first	Q - Science
author	Ping Li
spellingShingle	Ping Li misc QR1-502 misc influenza A virus misc chebulinic acid misc chebulagic acid misc neuraminidase misc neuraminidase inhibitor misc Microbiology Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors
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topic_title	QR1-502 Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors influenza A virus chebulinic acid chebulagic acid neuraminidase neuraminidase inhibitor
topic	misc QR1-502 misc influenza A virus misc chebulinic acid misc chebulagic acid misc neuraminidase misc neuraminidase inhibitor misc Microbiology
topic_unstemmed	misc QR1-502 misc influenza A virus misc chebulinic acid misc chebulagic acid misc neuraminidase misc neuraminidase inhibitor misc Microbiology
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title	Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors
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title_full	Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors
author_sort	Ping Li
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author_browse	Ping Li Ruikun Du Yanyan Wang Xuewen Hou Lin Wang Xiujuan Zhao Peng Zhan Xinyong Liu Lijun Rong Qinghua Cui
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title_sort	identification of chebulinic acid and chebulagic acid as novel influenza viral neuraminidase inhibitors
callnumber	QR1-502
title_auth	Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors
abstract	The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs.
abstractGer	The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs.
abstract_unstemmed	The influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are of a major public health concern. Although several antiviral drugs are currently available, there is an urgent need to develop novel antiviral therapies with different mechanisms of action due to emergence of drug resistance. In this study, two related compounds, chebulagic acid (CHLA) and chebulinic acid (CHLI), were identified as novel inhibitors against IAV replication. A reporter virus-based infection assay demonstrated that CHLA and CHLI exhibit no inhibitory effect on IAV entry or RNA replication during the virus replication cycle. Results of viral release inhibition assay and neuraminidase (NA) inhibition assay indicated that CHLA and CHLI exert their inhibitory effect on the NA-mediated viral release. Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI. In summary, CHLA and CHLI are promising new NA inhibitors that may be further developed as novel antivirals against IAVs.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700
title_short	Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors
url	https://doi.org/10.3389/fmicb.2020.00182 https://doaj.org/article/2784424ec4654f25bf0e2353aa8745cb https://www.frontiersin.org/article/10.3389/fmicb.2020.00182/full https://doaj.org/toc/1664-302X
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author2	Ruikun Du Yanyan Wang Xuewen Hou Lin Wang Xiujuan Zhao Peng Zhan Xinyong Liu Lijun Rong Qinghua Cui
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doi_str	10.3389/fmicb.2020.00182
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up_date	2024-07-03T17:53:40.493Z
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Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors

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