Phyllanthus tenellus Roxb. and Kaempferia parviflora Wall. ex Baker compounds as inhibitors of SARS-CoV-2 main protease and RNA-dependent RNA polymerase: A molecular docking study

Article published in J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1103-1116, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1485_10.6.1103

Suhaina Supian^*, Muhamad Aizuddin Ahmad, Lina Rozano, Machap Chandradevan, Zuraida Ab Rahman

Biotechnology and Nanotechnology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), Serdang 43400, Selangor, Malaysia.

*E-mail: suhaina@mardi.gov.my

Abstract

Context: The outbreak of a novel coronavirus, SARS-CoV-2 has caused an unprecedented COVID-19 pandemic. To put an end to this pandemic, effective antivirals should be identified or developed for COVID-19 treatment. However, specific and effective antivirals or inhibitors against SARS-CoV-2 are still lacking.

Aims: To evaluate bioactive compounds from Phyllanthus tenellus and Kaempferia parviflora as inhibitorsagainst two essential SARS-CoV-2 proteins, main protease (M^pro) and RNA-dependent RNA polymerase (RdRp), through molecular docking studies and to predict the drug-likeness properties of the compounds.

Methods: The inhibition potential and interaction of P. tenellus and K. parviflora compounds against M^pro and RdRp were assessed through molecular docking. The drug-likeness properties of the compounds were predicted using SwissADME and AdmetSAR tools.

Results: Rutin and ellagic acid glucoside from P. tenellus and 4-hydroxy-6-methoxyflavone and 5-hydroxy-3,7,4’-trimethoxyflavone from K. parviflora exhibited the highest binding conformations to M^proby interacting with its substrate binding site that was predicted to halt the M^pro activity. As for RdRp, ellagitannin and rutin from P. tenellus and peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were the best-docked compounds that bound to the RdRp catalytic domain (Asp760 and Asp761) and NTP-entry channel that were anticipated to stop RNA polymerization. However, in the context of drug developability, 4-hydroxy-6-methoxyflavone, 5-hydroxy-3,7,4’-trimethoxyflavone, peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were highly potential to be oral active drugs compared to rutin, ellagic acid glucoside and ellagitannin from P. tenellus.

Conclusions: P. tenellus and K. parviflora compounds, particularly the aforementioned compounds, were suggested as potential inhibitors of SARS-CoV-2 M^pro and RdRp.