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Unveiling the Potentiality of Shikonin Derivatives Inhibiting SARS-CoV-2 Main Protease by Molecular Dynamic Simulation Studies.
Das, Raju; Habiba, Sarmin Ummey; Dash, Raju; Seo, Yohan; Woo, Joohan.
  • Das R; Department of Physiology, Dongguk University College of Medicine, Gyeongju 38067, Republic of Korea.
  • Habiba SU; Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh.
  • Dash R; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea.
  • Seo Y; New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea.
  • Woo J; Department of Physiology, Dongguk University College of Medicine, Gyeongju 38067, Republic of Korea.
Int J Mol Sci ; 24(4)2023 Feb 04.
Article in English | MEDLINE | ID: covidwho-2256306
ABSTRACT
Shikonin, a phytochemical present in the roots of Lithospermum erythrorhizon, is well-known for its broad-spectrum activity against cancer, oxidative stress, inflammation, viruses, and anti-COVID-19 agents. A recent report based on a crystallographic study revealed a distinct conformation of shikonin binding to the SARS-CoV-2 main protease (Mpro), suggesting the possibility of designing potential inhibitors based on shikonin derivatives. The present study aimed to identify potential shikonin derivatives targeting the Mpro of COVID-19 by using molecular docking and molecular dynamics simulations. A total of 20 shikonin derivatives were screened, of which few derivatives showed higher binding affinity than shikonin. Following the MM-GBSA binding energy calculations using the docked structures, four derivatives were retained with the highest binding energy and subjected to molecular dynamics simulation. Molecular dynamics simulation studies suggested that alpha-methyl-n-butyl shikonin, beta-hydroxyisovaleryl shikonin, and lithospermidin-B interacted with two conserved residues, His41 and Cys145, through multiple bonding in the catalytic sites. This suggests that these residues may effectively suppress SARS-CoV-2 progression by inhibiting Mpro. Taken together, the present in silico study concluded that shikonin derivatives may play an influential role in Mpro inhibition.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Limits: Humans Language: English Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Limits: Humans Language: English Year: 2023 Document Type: Article