Phytochemicals as Potential Agents Against 3-Chymotrypsin Like Protease (3CLPro) in SARS-CoV-2

Date of Award


Degree Type


Degree Name

Master of Science in Biomedical Sciences

First Advisor

Srujana Rayalam, DVM, PhD

Second Advisor

Shashidharamurthy Taval, PhD

Third Advisor

Vicky Mody, PhD

Fourth Advisor

Valerie Cadet, PhD

Fifth Advisor

Lori Redmond, Ph.D


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, in December of 2019, is the causative agent for the global pandemic known as coronavirus disease 2019 (COVID-19). The outbreak of SARS-CoV-2 has triggered a number of studies to identify therapeutic approaches to stop the pandemic spread. In this study, we explore the potential of phytochemicals, that have been shown to exhibit anti-viral effects previously, as anti-SARS-CoV-2 agents. Previous studies indicated the importance of viral proteases in the replication of SARS-CoV-2. Among these proteases, papain-like protease and 3-chymotrypsinlike protease are involved in the synthesis of non-structural proteins responsible for the assembly of the replication-transcription complex. Phytochemicals such as, rutin, myricetin, and kaempferol, were reported as potential inhibitors of 3CLpro activity in silico. In the current study, we have screened 54 phytochemicals selected based on previous literature for their inhibitory effects on 3CLpro enzymatic activity using an in vitro 3CLpro enzymatic assay. Out of the 54 compounds tested, we observed about 50% inhibitory activity of 3CLpro enzymatic activity by theaflavin, myricetin, betulinic acid at 100μM concentration; and rutin, epigallocatechin gallate, and mangiferin at 200μM concentration. The IC50 values were as follows: theaflavin (79.07μM), myricetin (120.3μM), betulinic acid (71.20μM), epigallocatechin gallate (97.30μM), mangiferin (100.9μM), and rutin (3.83μM). In summary, our data indicates that selected phytochemicals exhibited anti-SARS-CoV-2 effects by targeting 3CLpro enzymatic activity. Additional in vitro and in vivo studies are required to confirm the potential of these phytochemicals as anti-SARS CoV-2 agents.

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