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Few extracts of plant species from the Brazilian flora have been validated from a pharmacological and clinical point of view, and it is important to determine whether their traditional use is proven by pharmacological effects.  Cenostigma pluviosum var. peltophoroides  is one of those plants, which belongs to the Fabaceae family that is widely used in traditional medicine and is very rich in tannins. Due to the lack of effective drugs to treat severe cases of Covid-19, the main protease of SARS-CoV-2 (M pro ) becomes an attractive target in the research for new antivirals since this enzyme is crucial for virus replication and does not have homologs in humans. This study aimed to prospect inhibitor candidates among the compounds from  C. pluviosum  extract, by virtual screening simulations using SARS-CoV-2 M pro  as target. Experimental validation was made by inhibitory proteolytic assays of recombinant M pro  and by antiviral activity with infected Vero cells. Docking simulations identify four compounds with potential inhibitory activity of M pro  present in the extract. The compound pentagalloylglucose showed the best result in proteolytic kinetics experiments, with suppression of recombinant M pro  activity by approximately 60%. However, in experiments with infected cells ethyl acetate fraction and sub-fractions, F2 and F4 of  C. pluviosum  extract performed better than pentagalloylglucose, reaching close to 100% of antiviral activity. The prominent activity of the extract fractions in infected cells may be a result of a synergistic effect from the different hydrolyzable tannins present, performing simultaneous action on M pro  and other targets from SARS-CoV-2 and host. Communicated by Ramaswamy H. Sarma

Antiviral activity of Cenostigma pluviosum var. peltophoroides extract and fractions against SARS-CoV-2