Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2
The continuous emergence of SARS-CoV-2 variants caused the persistence of the COVID-19 epidemic and challenged the effectiveness of the existing vaccines. The viral proteases are the most attractive targets for developing antiviral drugs. In this scenario, our study explores the use of HIV-1 proteas...
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MDPI AG
2024-02-01
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Online Access: | https://www.mdpi.com/1999-4915/16/3/338 |
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author | Davide Gentile Lucia Chiummiento Alessandro Santarsiere Maria Funicello Paolo Lupattelli Antonio Rescifina Assunta Venuti Anna Piperno Maria Teresa Sciortino Rosamaria Pennisi |
author_facet | Davide Gentile Lucia Chiummiento Alessandro Santarsiere Maria Funicello Paolo Lupattelli Antonio Rescifina Assunta Venuti Anna Piperno Maria Teresa Sciortino Rosamaria Pennisi |
author_sort | Davide Gentile |
collection | DOAJ |
description | The continuous emergence of SARS-CoV-2 variants caused the persistence of the COVID-19 epidemic and challenged the effectiveness of the existing vaccines. The viral proteases are the most attractive targets for developing antiviral drugs. In this scenario, our study explores the use of HIV-1 protease inhibitors against SARS-CoV-2. An in silico screening of a library of HIV-1 proteases identified four anti-HIV compounds able to interact with the 3CL<sup>pro</sup> of SARS-CoV-2. Thus, in vitro studies were designed to evaluate their potential antiviral effectiveness against SARS-CoV-2. We employed pseudovirus technology to simulate, in a highly safe manner, the adsorption of the alpha (α-SARS-CoV-2) and omicron (ο-SARS-CoV-2) variants of SARS-CoV-2 and study the inhibitory mechanism of the selected compounds for cell–virus interaction. The results reported a mild activity against the viral proteases 3CL<sup>pro</sup> and PL<sup>pro</sup>, but efficient inhibitory effects on the internalization of both variants mediated by cathepsin B/L. Our findings provide insights into the feasibility of using drugs exhibiting antiviral effects for other viruses against the viral and host SARS-CoV-2 proteases required for entry. |
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id | doaj.art-33477011c2c14ff4a9b9644772bd60c2 |
institution | Directory Open Access Journal |
issn | 1999-4915 |
language | English |
last_indexed | 2024-04-24T17:45:51Z |
publishDate | 2024-02-01 |
publisher | MDPI AG |
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spelling | doaj.art-33477011c2c14ff4a9b9644772bd60c22024-03-27T14:07:36ZengMDPI AGViruses1999-49152024-02-0116333810.3390/v16030338Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2Davide Gentile0Lucia Chiummiento1Alessandro Santarsiere2Maria Funicello3Paolo Lupattelli4Antonio Rescifina5Assunta Venuti6Anna Piperno7Maria Teresa Sciortino8Rosamaria Pennisi9Department of Chemistry, Materials and Chemical Engineering “G. Natta”, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, ItalyDepartment of Scienze, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Scienze, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Scienze, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Chimica, Sapienza University of Roma, p. le Aldo Moro 5, 00185 Roma, ItalyDepartment of Drug and Health Sciences, University of Catania, V. le A. Doria, 95125 Catania, ItalyInternational Agency for Research on Cancer (IARC), World Health Organization, 69366 LYON CEDEX 07, FranceDepartment of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyThe continuous emergence of SARS-CoV-2 variants caused the persistence of the COVID-19 epidemic and challenged the effectiveness of the existing vaccines. The viral proteases are the most attractive targets for developing antiviral drugs. In this scenario, our study explores the use of HIV-1 protease inhibitors against SARS-CoV-2. An in silico screening of a library of HIV-1 proteases identified four anti-HIV compounds able to interact with the 3CL<sup>pro</sup> of SARS-CoV-2. Thus, in vitro studies were designed to evaluate their potential antiviral effectiveness against SARS-CoV-2. We employed pseudovirus technology to simulate, in a highly safe manner, the adsorption of the alpha (α-SARS-CoV-2) and omicron (ο-SARS-CoV-2) variants of SARS-CoV-2 and study the inhibitory mechanism of the selected compounds for cell–virus interaction. The results reported a mild activity against the viral proteases 3CL<sup>pro</sup> and PL<sup>pro</sup>, but efficient inhibitory effects on the internalization of both variants mediated by cathepsin B/L. Our findings provide insights into the feasibility of using drugs exhibiting antiviral effects for other viruses against the viral and host SARS-CoV-2 proteases required for entry.https://www.mdpi.com/1999-4915/16/3/338SARS-CoV-2cysteine proteasepseudovirus technology |
spellingShingle | Davide Gentile Lucia Chiummiento Alessandro Santarsiere Maria Funicello Paolo Lupattelli Antonio Rescifina Assunta Venuti Anna Piperno Maria Teresa Sciortino Rosamaria Pennisi Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2 Viruses SARS-CoV-2 cysteine protease pseudovirus technology |
title | Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2 |
title_full | Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2 |
title_fullStr | Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2 |
title_full_unstemmed | Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2 |
title_short | Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2 |
title_sort | targeting viral and cellular cysteine proteases for treatment of new variants of sars cov 2 |
topic | SARS-CoV-2 cysteine protease pseudovirus technology |
url | https://www.mdpi.com/1999-4915/16/3/338 |
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