Identification of high-affinity inhibitors of SARS-CoV-2 main protease: Towards the development of effective COVID-19 therapy.

In this study, we utilized the structural information of co-crystallized SARS-CoV-2 Mpro for the structure-guided drug discovery approach to finding high-affinity inhibitors from the PubChem database. The screened compounds were selected on the basis of their physicochemical properties, drug-likeliness, and strength of affinity to the SARS-CoV-2 Mpro. Finally, we have identified 6-Deaminosinefungin (PubChem ID: 10428963) and UNII-O9H5KY11SV (PubChem ID: 71481120) as potential inhibitors of SARS-CoV-2 Mpro which may be further exploited in drug development to address SARS-CoV-2 pathogenesis. Both compounds are structural analogs of known antiviral compounds, having considerable protease inhibitory potential with improved pharmacological properties. All-atom molecular dynamics simulations suggested SARS-CoV-2 Mpro in complex with these compounds is stable during the simulation period with minimal structural changes. This work provides enough evidence for further implementation of the identified compounds in the development of effective therapeutics of COVID-19. PMID: 32717346 [PubMed - as supplied by publisher]
Source: Virus Research - Category: Virology Authors: Tags: Virus Res Source Type: research