Title:Discovery of a “Cocktail” of Potential SARS-COV-2 Main Protease Inhibitors through Virtual Screening of Known Chemical Components of Vitex negundo L. (“Lagundi”)
Volume: 18
Issue: 3
Author(s): Ruel Cayona*Evelyn Creencia
Affiliation:
- Department of Chemistry, College of Science and Mathematics, Mindanao State University - Iligan Institute of
Technology, Iligan City, Philippines
Keywords:
COVID-19, SARS-CoV-2 Mpro, V. negundo L., virtual screening, molecular docking, in silico ADMET, phytochemical mining, medicinal plants.
Abstract:
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: Vitex negundo 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 in silico 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 in silico 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 (e.g. 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 in silico 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.
