Identification of Berbamine, Oxyacanthine and Rutin from Berberis asiatica as anti-SARS-CoV-2 compounds: An in silico study.

ABSTRACT

Owing to the shortage of specific medicines, the global pandemic of COVID-19 caused by SARS-CoV-2 has been the greatest challenge for the science community. Researchers from all over the world developed some drugs which failed to completely suppress the contiguous disease. SARS-CoV-2 main protease (Mpro), an important component in viral pathogenesis, is considered as a prospective drug target to stop SARS-CoV-2 infection. Since identification of phytochemicals with anti-Mpro activity has been carried out to develop the potential drugs against SARS-CoV-2. Therefore, the present study was conducted to screen phytochemicals of Berberis asiatica for anti-SARS-CoV-2 activity. Through text mining, thirty phytochemicals were reported from B. asiatica, of which, three phytochemicals (Berbamine, Oxyacanthine, and Rutin) show high affinity with the SARS-CoV-2 Mpro and exhibited favorable intermolecular interactions with the catalytic residues (His41 and Cys145) and other essential residues. The molecular dynamics simulation showed that Mpro-phytochemical complexes are more stable, less fluctuating, more compact, and moderately extended than the Mpro-X77 (Reference) complex. The number of H-bonds and MMPBSA results also demonstrates that Berbamine, Oxyacanthine, and Rutin are potent Mpro inhibitors having free energy of -20.79, -33.35, and -31.12 kcal mol-1 respectively. The toxicity risk prediction supports all phytochemicals for drug-like and non-toxic nature. From the result, we propose that binding of these phytochemicals could hamper the function of Mpro. This work suggests that selected phytochemicals could be used as novel anti-COVID-19 drug candidates, and might act as novel compounds for in vitro and in vivo study.