Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2

Substantial research is currently conducted focusing on the development of promising antiviral drugs employing in silico screening and drug repurposing strategies against SARS-CoV-2. The current study aims at identifying lead molecules targeting SARS-CoV-2 by the application of in silico and molecular dynamics (MD) approaches from phytoconstituents present in Homalomena aromatica. The main protease (M-pro) enzyme of SARS-CoV-2 is taken as the target protein to perform the docking analysis of 71 molecules reported from H. aromatica by the application of different modules of Discovery Studio 2018. Five molecules were taken as prospective leads namely dihydrocuminaldehyde, p-cymen-8-ol, cuminaldehyde, p-cymene, and cuminol. In the absence of known inhibitors, a comparative study was performed with the compounds reported in the literature and potent terpenoid-metal complexes were taken into account based on known efficacy as anti-viral molecules. After performing the docking studies with Mpro enzyme of SARS-CoV-2, it was observed that the -CDocker Energy of cuminaldehyde thiosemicarbazone was 29.152, indicating a significant affinity toward Mpro. The same was also supported by the MD study. Taken together, our results provided in silico evidence that secondary metabolites derived from H. aromatica could be employed as potent antiviral agents targeting SARS-CoV-2. Our findings warrant further validation of their in vitro and in vivo efficacies prior to their development into bona fide therapeutic agents.