Identification of Potential Mpro Inhibitors for the Treatment of COVID-19 by Targeted Covalent Inhibition

Dushyant Patel, Divya Teli, Ashish Kanhed, Nirav Patel, Bhavik Shah, Amisha Vora, Mahesh Chhabria, Mange Yadav

OAI: oai:igi-global.com:269521 • DOI: 10.4018/IJQSPR.20210401.oa1

A novel coronavirus is the causative agent identified for the current COVID-19 outbreak. Globally, more than 43 million people have been infected by this virus. The total number of deaths has surpassed 1.6 million across 210 countries due to the current pandemic. Till date, there is no specific therapeutic agent available for its treatment. Mpro, a non-structural protein cleaves viral polyproteins into other non-structural proteins. Inhibition of Mpro could prevent the virus replication projecting it as a potential candidate for anti-COVID-19 drug development. The authors report herein 10 top-ranked curcumin derivatives as non-peptide covalent-binding Mpro inhibitors using systematic virtual screening approach. Detailed ligand-receptor interaction analysis conferred that the α,β-unsaturated carbonyl moiety of curcumin functions as a warhead to yield a Michael adduct with Cys145 of the catalytic dyad of Mpro. Collectively, these results have offered new high affinity molecules for the development of potential drugs for the treatment of COVID-19.

Chemistry Medical, Healthcare, and Life Sciences Chemistry