Details

Autor(en) / Beteiligte

• Basu, Soumya
• Veeraraghavan, Balaji
• Ramaiah, Sudha
• Anbarasu, Anand

Titel

Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease

Ist Teil von

• Microbial pathogenesis, 2020-12, Vol.149, p.104546-104546, Article 104546

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• No commercially available drug candidate has yet been devised which is unique to and not repurposed against SARS-CoV-2 and has high efficacy or safe toxicity profile or both. Taking curcumin as a reference compound, we identified a new commercially available cyclohexanone compound, ZINC07333416 with binding energy (−8.72 kcal/mol) better than that of popularly devised anti-Covid-19 drugs like viral protease inhibitor Lopinavir, nucleoside analogue Remdesivir and the repurposed drug hydroxychloroquine when targeted to the active-site of SARS-CoV-2 Main protease (Mpro) through docking studies. The ligand ZINC07333416 exhibits crucial interactions with major active site residues of SARS-CoV-2 Mpro viz. Cys145 and His41 involving in the protease activity; as well as GLU-166 and ASN-142 which plays the pivotal role in the protein-dimerization. The protein-ligand stable interaction was further confirmed with molecular dynamics simulation (MDS) studies. Based on virtual assessment, ZINC07333416 also have significant values in terms of medicinal chemistry, pharmacokinetics, synthetic accessibility and anti-viral activity that encourage its experimental applications against COVID-19. •A new commercially available cyclohexanone compound, ZINC07333416 was identified with good pharmacological profile and binding energy when docked with SARS-CoV-2 Main protease (Mpro).•The binding energy is better than that of protease inhibitor Lopinavir, nucleoside analogue Remdesivir. The ligand ZINC07333416 exhibits crucial interactions with major active site residues of SARS-CoV-2 Mpro viz. Cys145 and His41.•The protein-ligand stable interaction was further confirmed with molecular dynamics simulation (MDS) studies.