Session: Undergraduate Research Posters: Biochemistry:

The SARS-CoV-2 main protease (M^pro) is an internally encoded protease which serves to hydrolyze the translated polyproteins at designated sites. It directly mediates viral replication hence a promising and main target for drug design. Plant-based natural products provide scaffold for many effective antiviral medications, and are recently shown to be able to inhibit the SARS-CoV-2 M^pro. Polyphenols and phenolic compounds are a major class of bioactive natural compounds that are known for their antiviral and pleiotropic effects, which are also reported to be effective in M^pro activity inhibitions. This work focuses on the inhibition processes of M^pro with natural phenolic compounds found in Cacao. A recent experimental study supports that phenolic compounds in cacao have inhibitory effects against M^pro activities. We began by exploring the potential inhibitory activities of trans-clovamide, a naturally occurring caffeoyl conjugate that is found in the phenolic fraction of Theobroma Cacao L. Here, we propose inhibitory mechanisms by which clovamide acts as a M^pro inhibitor as it scavenges reactive oxygen species in the body. We use molecular docking and annealing-based molecular dynamics simulations to study the interactions between M^pro catalytic site residues and clovamide and its analogues. Our molecular modelling studies provide mechanistic insights of clovamide inhibition of M^pro, and indicate that clovamide may be a promising candidate as a drug lead molecule for COVID-19 treatments.

Miriam Rossi

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