In silico studies on structural inhibition of SARS-CoV-2 main protease M(pro) by major secondary metabolites of Andrographis paniculata and Cinchona officinalis

The COVID-19 infection by Novel Corona Virus (SARS-CoV-2) has become one of the largest pandemic diseases, with cumulative confirmed infections of 275,233,892 and 5,364,996 deaths to date according to World Health Organization. Due to the absence of any approved antiviral drug to treat COVID-19, its lethality is getting severe with time. The main protease of SARS-CoV-2, M(pro) is considered one of the potential drug targets because of its role in processing proteins translated from viral RNA. In the present study, four of the plant metabolites, 14-deoxy-11,12-didehydroandrographolide, andrograpanin, quinine, cinchonine from two eminent medicinal plants Andrographis paniculata and Cinchona officinalis, have been evaluated against the main protease of SARS-CoV-2 through in-silico molecular docking and molecular dynamics simulation study. From the result interpretations, it is found that andrograpanin has strong binding affinities with the target protein in its active site with potential negative energies. Molecular Dynamic simulation and MMGBSA studies suggest that earlier reported N3 inhibitor and andrograpanin exhibit effective binding interactions involving identical amino acid residues with the same binding pockets of the main protease of SARS-CoV-2. Therefore, the theoretical experiment suggests that andrograpanin, could be considered the promising inhibitor against SARS-CoV-2 M(pro). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11756-022-01012-y.