Plants Metabolites as In Vitro Inhibitors of SARS-CoV-2 Targets: A Systematic Review and Computational Analysis

Background/Objectives: Since the emergence of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of compounds with antiviral potential from medicinal plants has been extensively researched. This study aimed to investigate plant metabolites wit...

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Main Authors: Brendo Araujo Gomes, Diégina Araújo Fernandes, Thamirys Silva da Fonseca, Mariana Freire Campos, Patrícia Alves Jural, Marcos Vinicius Toledo e Silva, Larissa Esteves Carvalho Constant, Andrex Augusto Silva da Veiga, Beatriz Ribeiro Ferreira, Ellen Santos Magalhães, Hagatha Bento Mendonça Pereira, Beatriz Graziela Martins de Mattos, Beatriz Albuquerque Custódio de Oliveira, Stephany da Silva Costa, Flavia Maria Mendonça do Amaral, Danilo Ribeiro de Oliveira, Ivana Correa Ramos Leal, Gabriel Rocha Martins, Gilda Guimarães Leitão, Diego Allonso, Simony Carvalho Mendonça, Marcus Tullius Scotti, Suzana Guimarães Leitão
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Drugs and Drug Candidates
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Online Access:https://www.mdpi.com/2813-2998/4/2/27
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Summary:Background/Objectives: Since the emergence of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of compounds with antiviral potential from medicinal plants has been extensively researched. This study aimed to investigate plant metabolites with in vitro inhibitory potential against SARS-CoV-2 targets, including 3CL<sub>pro</sub>, PL<sub>pro</sub>, Spike protein, and RdRp. Methods: A systematic review was conducted following PRISMA guidelines, with literature searches performed in six electronic databases (Scielo, ScienceDirect, Scopus, Springer, Web of Science, and PubMed) from January 2020 to February 2024. Computational analyses using SwissADME, pkCSM, ADMETlab, ProTox3, Toxtree, and DataWarrior were performed to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles as well as other medicinal chemistry parameters of these compounds. Results: A total of 330 plant-derived compounds with inhibitory activities against the proposed targets were identified, with compounds showing IC<sub>50</sub> values as low as 0.01 μM. Our findings suggest that several plant metabolites exhibit significant in vitro inhibition of SARS-CoV-2 targets; however, few molecules exhibit drug development viability without further adjustments. Additionally, after these evaluations, two phenolic acids, salvianic acid A and protocatechuic acid methyl ester, stood out for their potential as candidates for developing antiviral therapies, with IC<sub>50</sub> values of 2.15 μM against 3CL<sub>pro</sub> and 3.76 μM against PL<sub>pro</sub>; respectively; and satisfactory in silico drug-likeness and ADMET profiles. Conclusions: These results reinforce the importance of plant metabolites as potential targets for antiviral drug discovery.
ISSN:2813-2998