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Binding mechanisms of Shikonin derivatives targeting SARS‐CoV‐2 main protease
Author(s) -
Woo JooHan,
Das Raju
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.l7672
Subject(s) - protease , in silico , chemistry , covid-19 , molecular dynamics , docking (animal) , binding energy , stereochemistry , combinatorial chemistry , biochemistry , enzyme , computational chemistry , gene , medicine , physics , nursing , disease , pathology , nuclear physics , infectious disease (medical specialty)
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 pro ) 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 pro 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 pro inhibition. Taken together, the present in silico study concluded that Shikonin derivatives might play an influential role against M pro inhibition.