Discovery of a "Cocktail" of Potential SARS-COV-2 Main Protease Inhibitors through Virtual Screening of Known Chemical Components of Vitex negundo L. ("Lagundi").

AIM

The prevailing crisis caused by COVID-19 pandemic demands the development of effective therapeutic agents that can be implemented with minimal to zero adverse effects.

BACKGROUND

L. (VNL) is a medicinal plant with reported efficacy against respiratory diseases and some of the COVID-19 symptoms. Funded by the Department of Science and Technology (DOST), the University of the Philippines - Philippine General Hospital (UP-PGH) is currently conducting clinical trials of VNL and other medicinal plants as adjuvant therapeutic agents against mild cases of COVID-19. The basis for the clinical trials is primarily the pharmacological efficacy of the medicinal plants against respiratory disorders and associated COVID-19 symptoms.

OBJECTIVE

This study assessed the potential of VNL components against SARS-CoV-2 main protease (Mpro), an enzyme that plays an important role in COVID-19, the disease caused by the SARS-CoV-2.

METHOD

Phytochemical mining of VNL components from the literature was conducted. A database consisting of 250 known compounds from different parts of VNL was created and screened against SARS-CoV-2 Mpro using PyRx virtual screening tool. The most promising components were further subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses using the SwissADME web server and Toxtree software.

RESULTS

Virtual screening revealed that 102 VNL components in the database had comparable to or better binding affinities toward SARS-COV-2 Mpro than known chemical inhibitors (. N3 and carmofur). It was determined that the active site of SARS-CoV-2 Mpro receptor consists of multiple H-donor and acceptor sites; hence, the most stable receptor-ligand complexes are generally formed by VNL ligands that establish effective H-bonding with the SARS-CoV-2 Mpro. The promising components, representing a "cocktail" of potential inhibitors also revealed interesting ADMET properties.

CONCLUSION

This study identified VNL as a potential single source of a cocktail of SARSCoV- 2 Mpro inhibitors and a promising adjuvant therapeutic agent against COVID-19 or its symptoms. Furthermore, the study offers a rationale on phytochemical mining from medicinal plants as a means that can be implemented in the early stage of a drug discovery and development program.