Azadirachtin-A a bioactive compound from Azadiracta indica is a potential inhibitor of SARS-CoV-2 main protease

Abstract

Despite the growing scientific interest in finding effective treatment, SARS-CoV-2 virus remains a global major health burden and public health emergency. SARS-CoV main protease (Mpro) also known as chymotrypsin-like protease (3CLpro) is an important protein identified to be vital for SARS-CoV-2 survival. However, to date, there are no clinically approved drugs or antibodies specific for SARS-CoV-2. In the present study, we evaluated the interaction of 3CLpro with azadirachtin-A a bioactive compound from Azadiracta indica using in silico molecular docking study. Our results revealed that Azadiractin A docked well into the binding cavity of 3CLproSARS-CoV-2 with binding affinities ranges between -6.3 and -5.20 kcal/mol, and Pkd of 5.82~6.10 for the ten best binding modes. Azadiractin interacted with the active site of 3CLpro-SARS-CoV-2 by 2 conventional hydrogen bonding to HIS163 and GLU166, C-H interactions with HIS127, and alkyl interaction with PRO168 of the 3CLpro-SARS-CoV-2. We also found that the Azadiractin-A_3CLpro-SARS-CoV-2 complex is stabilized by various Vander wall forces with ASN142, LEU141, PHE140, MET165, GLN189, LEU167, THR190, and ALA191. In conclusion, our results suggested that Azadirachtin-A could be a potential inhibitor of SARS-CoV-2 main protease, thus worthy of further preclinical study.