Article ; Online: Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents.
Communications biology
2021 Volume 4, Issue 1, Page(s) 93
Abstract: Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target ... ...
| Abstract | Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets. |
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| MeSH term(s) | Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; COVID-19/drug therapy ; COVID-19/virology ; Coronavirus 3C Proteases/antagonists & inhibitors ; Coronavirus 3C Proteases/chemistry ; Coronavirus 3C Proteases/metabolism ; Cysteine Proteinase Inhibitors/chemistry ; Cysteine Proteinase Inhibitors/pharmacology ; Drug Discovery ; Humans ; Ligands ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protein Binding ; Protein Conformation ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; Structure-Activity Relationship ; Virus Replication/drug effects |
| Chemical Substances | Antiviral Agents ; Cysteine Proteinase Inhibitors ; Ligands ; Coronavirus 3C Proteases (EC 3.4.22.28) |
| Language | English |
| Publishing date | 2021-01-20 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ISSN | 2399-3642 |
| ISSN (online) | 2399-3642 |
| DOI | 10.1038/s42003-020-01577-x |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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