Repurposing small molecules of against SARS-CoV-2 main protease.

Coronavirus infection is a communicable disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a global pandemic with deteriorating effect on the world's population. Main protease (M) of SARS-CoV-2 plays a significant role in the viral replication, transcription and disease propagation as well as a potential candidate for drug discovery and development for COVID-19 infection. The current study employed state of art structure-based drug discovery to decipher the role of phytochemicals of against M. is being used as a traditional medicinal plant for the treatment of cough, breathlessness and fever as per the Indian Materia Medica. Screening of the phytochemicals of against M was performed using molecular docking approach to identify the top 5 hits (+)-tephrorin B, deguelin, vitamin p, lanceolarin and 3beta-hydroxy-20(29)-lupene with binding energy of -8.4, -8.1, -8.0, -7.8, and -7.8 kcal/mol, respectively. Furthermore, identified top 5 hits were subjected to drug-likeness and toxicity prediction as well as MM-GBSA calculation. Out of the five molecules four molecules were predicted not to comprise any mutagenic and carcinogenic effects. Top two molecules based on the drug-likeness properties for oral bio-availability were further analysed by molecular dynamics simulation at 100 ns timescale. It was observed from the dynamic behaviour of the two complexes that the addition of these molecules changed the conformation and stability of the apo protein; thus may act as inhibitors for M.Communicated by Ramaswamy H. Sarma.