DigitalCommons@PCOM

In-vitro evaluation of inhibitory effect of nutraceuticals towards SARS-CoV-2 Papain Like Protease (PLpro) enzymatic activity

Suwanee, GA

The surge of the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2), that has led to the infection of COVID-19, has become a significant threat globally due to the high transmission rate of infection and mortality. Although vaccinations are available, breakthrough infections still occur with quick emerging variants. Currently, there are only a few drugs approved by FDA under emergency use authorization to treat COVID-19, however their adverse effects are of major concern. Therefore, it is important to pursue potential therapeutics to prevent the replication and viral spread of the SARS-CoV-2 virus. Several studies have shown that targeting viral proteases are better options to inhibit the viral replication. 3-chymotrypsin-like protease (3CLpro) and Papain-like protease (PLpro) are necessary proteases for coronaviruses’ replication. Among these two proteases, PLpro exhibits both proteolytic and deubiquitinase activity that promotes viral replication as well as disrupts the host cells' innate immune response when infected with the SARS-CoV-2. Based on previous studies, we selected 58 phytochemicals and performed in vitro SARS-CoV-2 PLpro enzymatic assay to screen the potential inhibitory effects. We have observed that the phytochemicals such as myricetin, theaflavin, tanshinone-I exhibited more than 80% inhibition activity at 50 μM concentrations with the IC50 values of 12.12 μM, 7.3 μM and 1.36 μM, respectively, whereas rutin, catechin, mangiferin, rhein, quercetin, oleuropein and γ-mangostin exhibited 60-70% inhibition at higher concentrations (100 and 200 μM). In summary, our data suggests that the tested phytochemicals selectively inhibited SARS-CoV-2 PLpro enzymatic activity, suggesting their potential use as anti-SARS-CoV-2 agents.