Potential Resistance of SARS-CoV-2 Main Protease (Mpro) against Protease Inhibitors: Lessons Learned from HIV-1 Protease
| Autor: | János András Mótyán, Jozsef Tozser, Gyula Hoffka, Mohamed Mahdi |
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| Rok vydání: | 2022 |
| Předmět: |
SARS-CoV-2
viruses Organic Chemistry General Medicine Antiviral Agents Catalysis COVID-19 Drug Treatment Computer Science Applications Molecular Docking Simulation Inorganic Chemistry HIV Protease Humans Protease Inhibitors Physical and Theoretical Chemistry Molecular Biology Coronavirus 3C Proteases Spectroscopy Peptide Hydrolases |
| Zdroj: | International Journal of Molecular Sciences. 23:3507 |
| ISSN: | 1422-0067 |
| Popis: | Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), has been one of the most devastating pandemics of recent times. The lack of potent novel antivirals had led to global health crises; however, emergence and approval of potent inhibitors of the viral main protease (Mpro), such as Pfizer’s newly approved nirmatrelvir, offers hope not only in the therapeutic front but also in the context of prophylaxis against the infection. By their nature, RNA viruses including human immunodeficiency virus (HIV) have inherently high mutation rates, and lessons learnt from previous and currently ongoing pandemics have taught us that these viruses can easily escape selection pressure through mutation of vital target amino acid residues in monotherapeutic settings. In this paper, we review nirmatrelvir and its binding to SARS-CoV-2 Mpro and draw a comparison to inhibitors of HIV protease that were rendered obsolete by emergence of resistance mutations, emphasizing potential pitfalls in the design of inhibitors that may be of important relevance to the long-term use of novel inhibitors against SARS-CoV-2. |
| Databáze: | OpenAIRE |
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