Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease
COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved...
Ausführliche Beschreibung
Autor*in: |
Xu, Yunxia [verfasserIn] Chen, Ke [verfasserIn] Pan, Juanli [verfasserIn] Lei, Yingshou [verfasserIn] Zhang, Danting [verfasserIn] Fang, Lipei [verfasserIn] Tang, Jinle [verfasserIn] Chen, Xin [verfasserIn] Ma, Yanhong [verfasserIn] Zheng, Yi [verfasserIn] Zhang, Bao [verfasserIn] Zhou, Yaoqi [verfasserIn] Zhan, Jian [verfasserIn] Xu, Wei [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: International journal of biological macromolecules - New York, NY [u.a.] : Elsevier, 1979, 188, Seite 137-146 |
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Übergeordnetes Werk: |
volume:188 ; pages:137-146 |
DOI / URN: |
10.1016/j.ijbiomac.2021.07.184 |
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Katalog-ID: |
ELV006605729 |
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520 | |a COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. | ||
650 | 4 | |a Papain-like protease | |
650 | 4 | |a Tanshinone IIA sulfonate sodium | |
650 | 4 | |a Chloroxine | |
700 | 1 | |a Chen, Ke |e verfasserin |4 aut | |
700 | 1 | |a Pan, Juanli |e verfasserin |4 aut | |
700 | 1 | |a Lei, Yingshou |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Danting |e verfasserin |4 aut | |
700 | 1 | |a Fang, Lipei |e verfasserin |4 aut | |
700 | 1 | |a Tang, Jinle |e verfasserin |4 aut | |
700 | 1 | |a Chen, Xin |e verfasserin |4 aut | |
700 | 1 | |a Ma, Yanhong |e verfasserin |4 aut | |
700 | 1 | |a Zheng, Yi |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Bao |e verfasserin |4 aut | |
700 | 1 | |a Zhou, Yaoqi |e verfasserin |4 aut | |
700 | 1 | |a Zhan, Jian |e verfasserin |4 aut | |
700 | 1 | |a Xu, Wei |e verfasserin |4 aut | |
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10.1016/j.ijbiomac.2021.07.184 doi (DE-627)ELV006605729 (ELSEVIER)S0141-8130(21)01644-5 DE-627 ger DE-627 rda eng 540 570 DE-600 BIODIV DE-30 fid 35.80 bkl 58.30 bkl Xu, Yunxia verfasserin aut Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. Papain-like protease Tanshinone IIA sulfonate sodium Chloroxine Chen, Ke verfasserin aut Pan, Juanli verfasserin aut Lei, Yingshou verfasserin aut Zhang, Danting verfasserin aut Fang, Lipei verfasserin aut Tang, Jinle verfasserin aut Chen, Xin verfasserin aut Ma, Yanhong verfasserin aut Zheng, Yi verfasserin aut Zhang, Bao verfasserin aut Zhou, Yaoqi verfasserin aut Zhan, Jian verfasserin aut Xu, Wei verfasserin aut Enthalten in International journal of biological macromolecules New York, NY [u.a.] : Elsevier, 1979 188, Seite 137-146 Online-Ressource (DE-627)30089502X (DE-600)1483284-7 (DE-576)259270814 1879-0003 nnns volume:188 pages:137-146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.80 Makromolekulare Chemie 58.30 Biotechnologie AR 188 137-146 |
spelling |
10.1016/j.ijbiomac.2021.07.184 doi (DE-627)ELV006605729 (ELSEVIER)S0141-8130(21)01644-5 DE-627 ger DE-627 rda eng 540 570 DE-600 BIODIV DE-30 fid 35.80 bkl 58.30 bkl Xu, Yunxia verfasserin aut Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. Papain-like protease Tanshinone IIA sulfonate sodium Chloroxine Chen, Ke verfasserin aut Pan, Juanli verfasserin aut Lei, Yingshou verfasserin aut Zhang, Danting verfasserin aut Fang, Lipei verfasserin aut Tang, Jinle verfasserin aut Chen, Xin verfasserin aut Ma, Yanhong verfasserin aut Zheng, Yi verfasserin aut Zhang, Bao verfasserin aut Zhou, Yaoqi verfasserin aut Zhan, Jian verfasserin aut Xu, Wei verfasserin aut Enthalten in International journal of biological macromolecules New York, NY [u.a.] : Elsevier, 1979 188, Seite 137-146 Online-Ressource (DE-627)30089502X (DE-600)1483284-7 (DE-576)259270814 1879-0003 nnns volume:188 pages:137-146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.80 Makromolekulare Chemie 58.30 Biotechnologie AR 188 137-146 |
allfields_unstemmed |
10.1016/j.ijbiomac.2021.07.184 doi (DE-627)ELV006605729 (ELSEVIER)S0141-8130(21)01644-5 DE-627 ger DE-627 rda eng 540 570 DE-600 BIODIV DE-30 fid 35.80 bkl 58.30 bkl Xu, Yunxia verfasserin aut Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. Papain-like protease Tanshinone IIA sulfonate sodium Chloroxine Chen, Ke verfasserin aut Pan, Juanli verfasserin aut Lei, Yingshou verfasserin aut Zhang, Danting verfasserin aut Fang, Lipei verfasserin aut Tang, Jinle verfasserin aut Chen, Xin verfasserin aut Ma, Yanhong verfasserin aut Zheng, Yi verfasserin aut Zhang, Bao verfasserin aut Zhou, Yaoqi verfasserin aut Zhan, Jian verfasserin aut Xu, Wei verfasserin aut Enthalten in International journal of biological macromolecules New York, NY [u.a.] : Elsevier, 1979 188, Seite 137-146 Online-Ressource (DE-627)30089502X (DE-600)1483284-7 (DE-576)259270814 1879-0003 nnns volume:188 pages:137-146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.80 Makromolekulare Chemie 58.30 Biotechnologie AR 188 137-146 |
allfieldsGer |
10.1016/j.ijbiomac.2021.07.184 doi (DE-627)ELV006605729 (ELSEVIER)S0141-8130(21)01644-5 DE-627 ger DE-627 rda eng 540 570 DE-600 BIODIV DE-30 fid 35.80 bkl 58.30 bkl Xu, Yunxia verfasserin aut Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. Papain-like protease Tanshinone IIA sulfonate sodium Chloroxine Chen, Ke verfasserin aut Pan, Juanli verfasserin aut Lei, Yingshou verfasserin aut Zhang, Danting verfasserin aut Fang, Lipei verfasserin aut Tang, Jinle verfasserin aut Chen, Xin verfasserin aut Ma, Yanhong verfasserin aut Zheng, Yi verfasserin aut Zhang, Bao verfasserin aut Zhou, Yaoqi verfasserin aut Zhan, Jian verfasserin aut Xu, Wei verfasserin aut Enthalten in International journal of biological macromolecules New York, NY [u.a.] : Elsevier, 1979 188, Seite 137-146 Online-Ressource (DE-627)30089502X (DE-600)1483284-7 (DE-576)259270814 1879-0003 nnns volume:188 pages:137-146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.80 Makromolekulare Chemie 58.30 Biotechnologie AR 188 137-146 |
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10.1016/j.ijbiomac.2021.07.184 doi (DE-627)ELV006605729 (ELSEVIER)S0141-8130(21)01644-5 DE-627 ger DE-627 rda eng 540 570 DE-600 BIODIV DE-30 fid 35.80 bkl 58.30 bkl Xu, Yunxia verfasserin aut Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. Papain-like protease Tanshinone IIA sulfonate sodium Chloroxine Chen, Ke verfasserin aut Pan, Juanli verfasserin aut Lei, Yingshou verfasserin aut Zhang, Danting verfasserin aut Fang, Lipei verfasserin aut Tang, Jinle verfasserin aut Chen, Xin verfasserin aut Ma, Yanhong verfasserin aut Zheng, Yi verfasserin aut Zhang, Bao verfasserin aut Zhou, Yaoqi verfasserin aut Zhan, Jian verfasserin aut Xu, Wei verfasserin aut Enthalten in International journal of biological macromolecules New York, NY [u.a.] : Elsevier, 1979 188, Seite 137-146 Online-Ressource (DE-627)30089502X (DE-600)1483284-7 (DE-576)259270814 1879-0003 nnns volume:188 pages:137-146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.80 Makromolekulare Chemie 58.30 Biotechnologie AR 188 137-146 |
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540 570 DE-600 BIODIV DE-30 fid 35.80 bkl 58.30 bkl Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease Papain-like protease Tanshinone IIA sulfonate sodium Chloroxine |
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Xu, Yunxia Chen, Ke Pan, Juanli Lei, Yingshou Zhang, Danting Fang, Lipei Tang, Jinle Chen, Xin Ma, Yanhong Zheng, Yi Zhang, Bao Zhou, Yaoqi Zhan, Jian Xu, Wei |
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repurposing clinically approved drugs for covid-19 treatment targeting sars-cov-2 papain-like protease |
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Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease |
abstract |
COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. |
abstractGer |
COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. |
abstract_unstemmed |
COVID-19 is a disease caused by SARS-CoV-2, which has led to more than 4 million deaths worldwide. As a result, there is a worldwide effort to develop specific drugs for targeting COVID-19. Papain-like protease (PLpro) is an attractive drug target because it has multiple essential functions involved in processing viral proteins, including viral genome replication and removal of post-translational ubiquitination modifications. Here, we established two assays for screening PLpro inhibitors according to protease and anti-ISGylation activities, respectively. Application of the two screening techniques to the library of clinically approved drugs led to the discovery of tanshinone IIA sulfonate sodium and chloroxine with their IC50 values of lower than 10 μM. These two compounds were found to directly interact with PLpro and their molecular mechanisms of binding were illustrated by docking and molecular dynamics simulations. The results highlight the usefulness of the two developed screening techniques for locating PLpro inhibitors. |
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Repurposing clinically approved drugs for COVID-19 treatment targeting SARS-CoV-2 papain-like protease |
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Chen, Ke Pan, Juanli Lei, Yingshou Zhang, Danting Fang, Lipei Tang, Jinle Chen, Xin Ma, Yanhong Zheng, Yi Zhang, Bao Zhou, Yaoqi Zhan, Jian Xu, Wei |
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score |
7.3985195 |