Identification of Anti-HIV/Migraine Drugs as Potential Inhibitors of SARS-Cov2 Main Protease Using in Silico Assessments

Background: The acute respiratory syndrome named “COVID-19” is caused by a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Lack of specific antiviral drugs or proper vaccination has led to the development of new therapeutic methods against this virus. Objective The Mpro 3Clpro is the main protease of the SARS-CoV-2 which plays an important role in replication and transcription of the virus. Therefore, targeting this enzyme is a valuable approach for drug development. Methods: In the present study, the structural properties of 69 anti-migraine and 212 anti-HIV drugs were first obtained from Drug Bank database. To select the appropriate drugs for the enzyme inhibition, the AutoDock Vina software was used. The molecular dynamics (MD) simulation method was applied for better recognition of the structural changes. Results: We identified Rimegepant (PubChem ID: 51049968), Dihydroergotamine (PubChem ID: 10531) and Ergotamine (PubChem ID: 8223) as potential inhibitors of Mpro 3Clpro. These complexes were equilibrated after 70 ns. Conclusion: Among these compounds, the anti-migraine drug “Rimegepant” showed the highest affinity for binding to the Mpro 3Clpro (-60.8 kJ/mol). This study provides enough evidence for further accomplishment of the identified compounds in the development of effective therapeutics methods against COVID-19.