In silico screening of potential inhibitors from Cordyceps species against SARS-CoV-2 main protease

Abstract

Coronavirus disease 2019 (COVID-19) is a result of a retroviral infection of SARS-CoV-2. Due to its virulence and high infection rate, it is a matter of serious concern and a global health emergency. Currently available COVID-19 vaccines approved by regulatory bodies around the world have been shown to provide significant protection against COVID-19. But no vaccine is 100% effective at preventing infection, also they have varying efficacy rates and different side effects. However, the main protease (Mpro) of SARS-CoV-2 has been identified as a key drug target due to its essential role in viral infection and its minimal similarity with human proteases. Cordyceps mushrooms have been found to have various therapeutic properties that could effectively combat SARS-CoV-2, including improve lung functioning, anti-viral, immunomodulators, anti-infectious, and anti-inflammatory. The present study aims to screen and evaluate the inhibitory potential of the bioactive molecules from the Cordyceps species against the Mpro of SARS-CoV-2. The bioactive molecules were screened based on their docking score, molecular interactions in the binding pocket, ADME properties, toxicity, carcinogenicity, and mutagenicity. Among all the molecules that were tested, cordycepic acid was the most effective and promising candidate, with a binding affinity of -8.10 kcal/mol against Mpro. The molecular dynamics (MD) simulation and free binding energy calculations revealed that the cordycepic acid-Mpro complex was highly stable and showed fewer conformational fluctuations. These findings need to be investigated further through in-vitro and in-vivo studies for additional validation.Communicated by Ramaswamy H. Sarma.

Keywords: SARS-CoV-2; cordyceps; molecular docking; molecular dynamics; mpro.