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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MDPI AG
2025-06-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Brendo Araujo Gomes |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-69b4e5afdf7c48c598e9d45810372425 |
| institution | OA Journals |
| issn | 2813-2998 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Drugs and Drug Candidates |
| spelling | doaj-art-69b4e5afdf7c48c598e9d458103724252025-08-20T02:24:29ZengMDPI AGDrugs and Drug Candidates2813-29982025-06-01422710.3390/ddc4020027Plants Metabolites as In Vitro Inhibitors of SARS-CoV-2 Targets: A Systematic Review and Computational AnalysisBrendo Araujo Gomes0Diégina Araújo Fernandes1Thamirys Silva da Fonseca2Mariana Freire Campos3Patrícia Alves Jural4Marcos Vinicius Toledo e Silva5Larissa Esteves Carvalho Constant6Andrex Augusto Silva da Veiga7Beatriz Ribeiro Ferreira8Ellen Santos Magalhães9Hagatha Bento Mendonça Pereira10Beatriz Graziela Martins de Mattos11Beatriz Albuquerque Custódio de Oliveira12Stephany da Silva Costa13Flavia Maria Mendonça do Amaral14Danilo Ribeiro de Oliveira15Ivana Correa Ramos Leal16Gabriel Rocha Martins17Gilda Guimarães Leitão18Diego Allonso19Simony Carvalho Mendonça20Marcus Tullius Scotti21Suzana Guimarães Leitão22Programa de Pós-Graduação em Biotecnologia Vegetal e Bioprocessos, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilInstituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro 21941-902, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilPrograma de Pós-Graduação em Biotecnologia Vegetal e Bioprocessos, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilLaboratório de Biotecnologia e Bioengenharia Estrutural, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro 21941-902, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilPrograma de Pós-Graduação em Biotecnologia Vegetal e Bioprocessos, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilLaboratório de Biotecnologia e Bioengenharia Estrutural, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro 21941-902, RJ, BrazilLaboratório de Biotecnologia e Bioengenharia Estrutural, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro 21941-902, RJ, BrazilDepartamento de Farmácia, Universidade Federal do Maranhão, São Luis 65085-580, MA, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilFaculdade de Ciências Farmacêuticas, Departamento de Farmácia, Universidade de São Paulo, São Paulo 05508-900, SP, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilDepartamento de Química, Universidade Federal da Paraíba, João Pessoa 58051-970, PB, BrazilPrograma de Pós-Graduação em Biotecnologia Vegetal e Bioprocessos, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilBackground/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.https://www.mdpi.com/2813-2998/4/2/27natural products3CL<sub>pro</sub>PL<sub>pro</sub>Spike:ACE2RdRpADMET profiling |
| spellingShingle | 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 Plants Metabolites as In Vitro Inhibitors of SARS-CoV-2 Targets: A Systematic Review and Computational Analysis Drugs and Drug Candidates natural products 3CL<sub>pro</sub> PL<sub>pro</sub> Spike:ACE2 RdRp ADMET profiling |
| title | Plants Metabolites as In Vitro Inhibitors of SARS-CoV-2 Targets: A Systematic Review and Computational Analysis |
| title_full | Plants Metabolites as In Vitro Inhibitors of SARS-CoV-2 Targets: A Systematic Review and Computational Analysis |
| title_fullStr | Plants Metabolites as In Vitro Inhibitors of SARS-CoV-2 Targets: A Systematic Review and Computational Analysis |
| title_full_unstemmed | Plants Metabolites as In Vitro Inhibitors of SARS-CoV-2 Targets: A Systematic Review and Computational Analysis |
| title_short | Plants Metabolites as In Vitro Inhibitors of SARS-CoV-2 Targets: A Systematic Review and Computational Analysis |
| title_sort | plants metabolites as in vitro inhibitors of sars cov 2 targets a systematic review and computational analysis |
| topic | natural products 3CL<sub>pro</sub> PL<sub>pro</sub> Spike:ACE2 RdRp ADMET profiling |
| url | https://www.mdpi.com/2813-2998/4/2/27 |
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