Presenting Author Dongguk University Gyeongju, Kyongsang-bukto, Republic of Korea
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 (Mpro) 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 Mpro 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 Mpro inhibition. Taken together, the present in silico study concluded that Shikonin derivatives might play an influential role against Mpro inhibition.
lt;agt;This research was funded by the National Research Foundation of Korea, grant numbers NRF-2019R1F1A1063245 and the Dongguk University Research Program of 2021.lt;/agt;
Separated binding orientation and 2D interactions map of active amino acids of Main protease of SARS-CoV-2 with different shikonin derivatives obtained from XP molecular docking; Secondary structural elements of Main protease of SARS CoV-2 in A) Apo, Shiko -nin, C) Shikonin Glucoside, D) 4-chlorophenylacetyl shikonin, E) Lithospermidin B, F) Angelyshikonin.
