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Antiviral treatments inhibiting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication may represent a strategy complementary to vaccination to fight the ongoing Coronavirus disease 19 (COVID-19) pandemic. Molecules or extracts inhibiting the SARS-CoV-2 chymotripsin-like protease (3CL Pro ) could contribute to reducing or suppressing SARS-CoV-2 replication. Using a targeted approach, we identified 17 plant products that are included in current and traditional cuisines as promising inhibitors of SARS-CoV-2 3CL Pro activity. Methanolic extracts were evaluated in vitro for inhibition of SARS-CoV-2 3CL Pro activity using a quenched fluorescence resonance energy transfer (FRET) assay. Extracts from turmeric ( Curcuma longa ) rhizomes, mustard ( Brassica nigra ) seeds, and wall rocket (Diplotaxis erucoides subsp. erucoides ) at 500 µg mL -1 displayed significant inhibition of the 3CL Pro activity, resulting in residual protease activities of 0.0%, 9.4%, and 14.9%, respectively. Using different extract concentrations, an IC 50 value of 15.74 µg mL -1 was calculated for turmeric extract. Commercial curcumin inhibited the 3CL Pro activity, but did not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that other components of the turmeric extract must also play a main role in inhibiting the 3CL Pro activity. Sinigrin, a major glucosinolate present in mustard seeds and wall rocket, did not have relevant 3CL Pro inhibitory activity; however, its hydrolysis product allyl isothiocyanate had an IC 50 value of 41.43 µg mL -1 . The current study identifies plant extracts and molecules that can be of interest in the search for treatments against COVID-19, acting as a basis for future chemical, in vivo, and clinical trials.

Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity