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

Abstract

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 (3CLPro) 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 3CLPro activity. Methanolic extracts were evaluated in vitro for inhibition of SARS-CoV-2 3CLPro 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 3CLPro activity, resulting in residual protease activities of 0.0%, 9.4%, and 14.9%, respectively. Using different extract concentrations, an IC50 value of 15.74 µg mL−1 was calculated for turmeric extract. Commercial curcumin inhibited the 3CLPro 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 3CLPro activity. Sinigrin, a major glucosinolate present in mustard seeds and wall rocket, did not have relevant 3CLPro inhibitory activity; however, its hydrolysis product allyl isothiocyanate had an IC50 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.

Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention

“…Curcumin, being already explored in vitro as a potent inhibitor of SARS-CoV M pro with an IC 50 value of 20 µM [82], is considered a promising natural polyphenol for mitigating the severity of COVID-19 disease. Indeed, the concentrations of curcumin above 30 µg/mL reduced the activity of SARS-CoV 2 M pro by more than 50%, while the higher concentration of 75 µg/mL produced residual activity of 28.1% [83]. Besides M pro , this molecule can also inhibit PL pro from SARS-CoV, with an IC 50 of 5.7 µM [82].…”

Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth

“…Only very few in vitro -tested models of curcumin for COVID-19 treatment were investigated using Vero E6 cells or human Calu-3 cells that were infected with SARS-CoV-2 ( Bormann et al, 2021 ). The data revealed that in vitro models treated with curcumin, nano-curcumin formulation, or turmeric root extracts could neutralize and decrease the SARS-CoV-2 viral RNA level at low subtoxic concentrations ( Guijarro-Real et al, 2021 ; Pourhajibagher et al, 2021 ). Another biochemical and enzyme activity tests showed that the turmeric root extract can significantly constrain the main protease (M pro ) activity of SARS-CoV-2 ( Dound et al, 2021 ).…”

Antiviral phytocompounds “ellagic acid” and “(+)-sesamin” of Bridelia retusa identified as potential inhibitors of SARS-CoV-2 3CL pro using extensive molecular docking, molecular dynamics simulation studies, binding free energy calculations, and bioactivity prediction

“…Many plants such as Lycoris radiata , Artemisia annua , Pyrrosia lingaua , Lindera aggregata , Isatis indigotica , Torreya nucifera , Houttuynia cordata , Echinacea , Cinchona , Curcuma longa , and Curcuma xanthorrhiza have been reported to contain antiviral phytoconstituents that might be effective against SARS-CoV-2 [ 18 – 20 ]. A study reported that selected herbal extracts have the potential to inhibit SARS-CoV-2 [ 21 ]. Another study reported that the polyphenolic leaf extract of Vitis vinifera inhibited in vitro replication of SARS-CoV-2 [ 22 ].…”