Binding mechanisms of Shikonin derivatives targeting SARS-CoV-2 main protease.

Shikonin, a well-known bioactive chemical present in the dried roots of Lithospermum erthrorhizon, is recognized for its broad-spectrum activities against cancer, oxidative stress, inflammation, virus, and anti-COVID-19 agent. In recent discovery, the crystallographic study of Shikonin bound Main protease (M ) of SARS CoV-2 revealed different conformation, suggesting the possibility of designing Shikonin derivatives as potential inhibitors of Covid. Towards the goal, the present study is carried out to explore insights of Shikonin derivatives and find out the possibility of Shikonin derivatives targeting M of Covid by using molecular docking and molecular dynamics simulation. A total of 25 Shikonin derivatives are introduced in this study, from where seven derivatives showed higher binding affinity than Shikonin, while four derivatives obtained the highest binding energy in MM-GBSA binding energy calculation. According to Molecular dynamics simulation results, all compounds interact with two conserved His41 and Cys145 residues through multiple bonding in the catalytic sites, suggesting that these derivatives may effectively terminate SARS COV-2 progression via M inhibition. Taken together, the present in silico study concluded that Shikonin derivatives might play an influential role against M inhibition.