Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease
2019 (COVID-19). SARS-CoV-2 is known for its high pathogenicity and transmission due to the
presence of polybasic cleavage sites. No specific drug is available for the treatment. To identify
the potential inhibitors, we have performed molecular docking against the SARS-CoV-2 main
protease (6Y84) with fifteen important natural xanthone compounds. The docking results showed
all the compounds exhibited good binding energies and interactions with the main protease. The
validation of representative docking complexes through molecular dynamics simulations showed
that xanthones binds with a higher binding affinity and lower free energy than the standard
ligand with Brasixanthone C and Brasixanthone B on 50 ns. Natural xanthone compounds have
also passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property criteria
as well as Lipinski’s rule of five. The present integrated molecular docking and dynamics
simulations study unveil the use of xanthones as potential antiviral agents against SARS-CoV-2.