Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved..
Effective control of COVID-19 requires antivirals directed against SARS-CoV-2. We assessed 10 hepatitis C virus (HCV) protease-inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity of the substrate binding clefts of SARS-CoV-2 main protease (Mpro) and HCV NS3/4A protease. Virtual docking experiments show that these HCV drugs can potentially bind into the Mpro substrate-binding cleft. We show that seven HCV drugs inhibit both SARS-CoV-2 Mpro protease activity and SARS-CoV-2 virus replication in Vero and/or human cells. However, their Mpro inhibiting activities did not correlate with their antiviral activities. This conundrum is resolved by demonstrating that four HCV protease inhibitor drugs, simeprevir, vaniprevir, paritaprevir, and grazoprevir inhibit the SARS CoV-2 papain-like protease (PLpro). HCV drugs that inhibit PLpro synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, increasing remdesivir's antiviral activity as much as 10-fold, while those that only inhibit Mpro do not synergize with remdesivir.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Cell reports - 35(2021), 7 vom: 18. Mai, Seite 109133 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bafna, Khushboo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.05.2021 Date Revised 16.02.2024 published: Print-Electronic UpdateOf: ChemRxiv. 2020 Apr 21;:. - PMID 32511291 Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2021.109133 |
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| PPN (Katalog-ID): |
NLM325356483 |
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| 245 | 1 | 0 | |a Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture |
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| 500 | |a Date Revised 16.02.2024 | ||
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| 500 | |a UpdateOf: ChemRxiv. 2020 Apr 21;:. - PMID 32511291 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Effective control of COVID-19 requires antivirals directed against SARS-CoV-2. We assessed 10 hepatitis C virus (HCV) protease-inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity of the substrate binding clefts of SARS-CoV-2 main protease (Mpro) and HCV NS3/4A protease. Virtual docking experiments show that these HCV drugs can potentially bind into the Mpro substrate-binding cleft. We show that seven HCV drugs inhibit both SARS-CoV-2 Mpro protease activity and SARS-CoV-2 virus replication in Vero and/or human cells. However, their Mpro inhibiting activities did not correlate with their antiviral activities. This conundrum is resolved by demonstrating that four HCV protease inhibitor drugs, simeprevir, vaniprevir, paritaprevir, and grazoprevir inhibit the SARS CoV-2 papain-like protease (PLpro). HCV drugs that inhibit PLpro synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, increasing remdesivir's antiviral activity as much as 10-fold, while those that only inhibit Mpro do not synergize with remdesivir | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a HCV protease inhibitors | |
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| 700 | 1 | |a Montelione, Gaetano T |e verfasserin |4 aut | |
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