Potential of plant extracts in targeting SARS-CoV-2 main protease: an in vitro and in silico study

Abstract

The deaths caused by the covid-19 pandemic have recently decreased due to a worldwide effort in vaccination campaigns. However, even vaccinated people can develop a severe form of the disease that requires ICU admission. As a result, the search for antiviral drugs to treat these severe cases has become a necessity. In this context, natural products are an interesting alternative to synthetic medicines used in drug repositioning, as they have been consumed for a long time through traditional medicine. Many natural compounds found in plant extracts have already been shown to be effective in treating viral and bacterial diseases, making them possible hits to exploit against covid-19. The objective of this work was to evaluate the antiviral activity of different plant extracts available in the library of natural products of the Universidade Estadual de Maringá, by inhibiting the SARS-CoV-2 main protease (M^pro), and by preventing viral infection in a cellular model. As a result, the extract of Cytinus hypocistis, obtained by ultrasound, showed a M^pro inhibition capacity greater than 90%. In the infection model assays using Vero cells, an inhibition of 99.6% was observed, with a selectivity index of 42.7. The in silico molecular docking simulations using the extract compounds against M^pro, suggested Tellimagrandin II as the component of C. hypocistis extract most likely to inhibit the viral enzyme. These results demonstrate the potential of C. hypocistis extract as a promising source of natural compounds with antiviral activity against covid-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• covid-19
• Cytinus hypocistis
• tannins
• Tellimagrandin II

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by Coordination for the Improvement of Higher Education Personnel - Brazil (CAPES) - Code 001 and project number 88887.505029/2020-00, and by Araucária Foundation (agreement 87/2021). The authors thank FINEP and COMCAP/UEM for the facilities, and CENAPAD/SP for the computational resources (projects 520 and 870). The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES (PIDDAC) to CIMO (UIDB/00690/2020 and UIDP/00690/2020) and SusTEC (LA/P/0007/2020). A. R. Silva is grateful to FCT and FSE for her Doctoral Grant (SFRH/BD/145834/2019) and L. Barros for her contract through the institutional scientific employment program-contract.