Discovery of potent inhibitors for M^pro enzyme of SARS-COV2 by multi-stage in-silico screening of Alkannin/shikonin

Abstract

Novel coronavirus disease, a serious challenge for the healthcare system, has diverted all the researchers toward the exploration of potential targets, compounds or vaccines for the management of this disease. M^pro enzyme was found to be crucial for replication of this virus which makes this enzyme an attractive drug target for SARS-CoV-2. Diverse pharmacological profile of Alkannin/shikonin (A/S) derivatives build up curiosity to study their antiviral profile. Therefore, current study utilises various computational tools to screen and evaluate all the discovered A/S derivatives to inhibit the M^pro enzyme for its anti-viral activity. Results revealed that the A/S has a very good tendency to inhibit the catalytic activity of the enzyme. Moreover, (5 R,6R)-5,8-dihydroxy-6-methoxy-3,4,5,6-tetrahydro-2H-benzo[a]anthracene-1, 7, 12-trione, an A/S derivative was found to possess drug-likeliness properties and a good ADME profile. Moreover, its complex with Mpro enzyme was found stable for 50 ns which makes it a very promising ligand to treat COVID-19.

Graphical Abstract

KEYWORDS:

• Alkannin/shikonin
• M^pro enzyme
• SARS-COV2
• molecular dynamic simulation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Component 4 of Rashtriya Uchchatar Shiksha Abhiyan (RUSA) scheme 2.0. The authors are also thankful to, Dassault Systèmes BIOVIA, DE Shaw Desmond and Guru Nanak Dev University, Amritsar for providing various basic facilities to complete the work.