Naturally occurring anthraquinones as potential inhibitors of SARS-CoV-2 main protease: an integrated computational study

The novel coronavirus disease (COVID-19) has spread throughout the globe, affecting millions of people. The World Health Organization (WHO) has declared this infectious disease a pandemic. At present, several clinical trials are going on to identify possible drugs for treating this infection. SARS-CoV-2 M(pro) is one of the most critical drug targets for the blockage of viral replication. The aim of this study was to identify potential natural anthraquinones that could bind to the active site of SARS-CoV-2 main protease and stop the viral replication. Blind molecular docking studies of 13 anthraquinones and one control drug (Boceprevir) with SARS-CoV-2 M(pro) were carried out using the SwissDOCK server, and alterporriol-Q that showed the highest binding affinity towards M(pro) were subjected to molecular dynamics simulation studies. This study indicated that several antiviral anthraquinones could prove to be effective inhibitors for SARS-CoV-2 M(pro) of COVID-19 as they bind near the active site having the catalytic dyad, HIS41 and CYS145 through non-covalent forces. The anthraquinones showed less inhibitory potential as compared to the FDA-approved drug, boceprevir. Among the anthraquinones studied, alterporriol-Q was found to be the most potent inhibitor of SARS-CoV-2 M(pro). Further, MD simulation studies for M(pro)- alterporriol-Q system suggested that alterporriol-Q does not alter the structure of M(pro) to a significant extent. Considering the impact of COVID-19, identification of alternate compounds like alterporriol-Q that could inhibit the viral infection will help in accelerating the process of drug discovery. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11756-021-01004-4.