Natural compounds from ethno-medicinal plants exhibit multiple binding activities on SARS-CoV-2 spike protein receptor-binding domains

BackgroundCOVID-19, caused by SARS-CoV-2, is a communicable respiratory viral disease with no effective curative medicine. The structure of SARS-CoV-2 spike protein has conserved modules that facilitate both infection and fusion into human host cells. These modules serve as crucial targets for synth...

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Main Authors: Trizah K. Milugo, Bethwell Owuor, Patrick W. Okanya, Kennedy Chepukosi, George F. Obiero
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Natural Products
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Online Access:https://www.frontiersin.org/articles/10.3389/fntpr.2025.1597609/full
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author Trizah K. Milugo
Trizah K. Milugo
Bethwell Owuor
Patrick W. Okanya
Kennedy Chepukosi
George F. Obiero
author_facet Trizah K. Milugo
Trizah K. Milugo
Bethwell Owuor
Patrick W. Okanya
Kennedy Chepukosi
George F. Obiero
author_sort Trizah K. Milugo
collection DOAJ
description BackgroundCOVID-19, caused by SARS-CoV-2, is a communicable respiratory viral disease with no effective curative medicine. The structure of SARS-CoV-2 spike protein has conserved modules that facilitate both infection and fusion into human host cells. These modules serve as crucial targets for synthesized and natural antivirals and therapeutics. In this study, our objective was to explore the potential of ethno-medicinal practice and molecular modelling of phytochemicals in informing drug targets against COVID-19 infections.MethodsThe study was conducted at four sites in western Kenya’s Lake Victoria basin. We used purposive sampling and snowballing to identify traditional health practitioners (THPs) and documented their experience and response to COVID-19. Extracts from various medicinal plants identified by the THP were subjected to phytochemical analysis on Gas Chromatography-Mass-spectrometry (GC-MS). The resulting active phytochemicals were screened against SARS-CoV-2 S-protein in silico using molecular modelling tools.ResultsSeventeen (17) THPs with experience in response to COVID-19 were identified, of whom 92% had more than 10 years of experience in the practice of traditional medicine. Whereas 43 medical plants were identified and documented, only seven plants, prescribed consistently by all THPs were investigated further. Phytochemical analysis on GC-MS identified compounds belonging to different chemical classes: terpenes, alkanes, alkene, alcohols, acridone, pyrazine, and carboxylic acid esters. Molecular modelling revealed the S-protein to possess multiple active sites. The phytochemicals studied showed potential multiple conformers interacting with each of the S-protein active sites.ConclusionOverall, we identified and modelled phytochemicals with the SARS-CoV-2 S-protein and explained their bioactivities as reported by traditional herbalists. The study underscores the beneficial contribution of traditional medicine in settings where access to comprehensive healthcare services for COVID-19 is limited. The identified plants and/or their phytochemicals could be targeted for conservation and future investigations including in-vivo studies targeting different aspects of the virus replication process, followed by the development of drugs with novel mode of action. The phytochemicals can also be screened for activities against other viruses in the Coronaviridae family.
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spelling doaj-art-e7ef3b891e79463b9a959f7ddde1838d2025-08-20T02:56:07ZengFrontiers Media S.A.Frontiers in Natural Products2813-26022025-05-01410.3389/fntpr.2025.15976091597609Natural compounds from ethno-medicinal plants exhibit multiple binding activities on SARS-CoV-2 spike protein receptor-binding domainsTrizah K. Milugo0Trizah K. Milugo1Bethwell Owuor2Patrick W. Okanya3Kennedy Chepukosi4George F. Obiero5Department of Biological and Life Sciences The Technical University of Kenya, Nairobi, KenyaMedical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, GambiaBiological Sciences Department, Kisii University, Kisii, KenyaDepartment of Biological and Life Sciences The Technical University of Kenya, Nairobi, KenyaDepartment of Biological and Life Sciences The Technical University of Kenya, Nairobi, KenyaDepartment of Biological and Life Sciences The Technical University of Kenya, Nairobi, KenyaBackgroundCOVID-19, caused by SARS-CoV-2, is a communicable respiratory viral disease with no effective curative medicine. The structure of SARS-CoV-2 spike protein has conserved modules that facilitate both infection and fusion into human host cells. These modules serve as crucial targets for synthesized and natural antivirals and therapeutics. In this study, our objective was to explore the potential of ethno-medicinal practice and molecular modelling of phytochemicals in informing drug targets against COVID-19 infections.MethodsThe study was conducted at four sites in western Kenya’s Lake Victoria basin. We used purposive sampling and snowballing to identify traditional health practitioners (THPs) and documented their experience and response to COVID-19. Extracts from various medicinal plants identified by the THP were subjected to phytochemical analysis on Gas Chromatography-Mass-spectrometry (GC-MS). The resulting active phytochemicals were screened against SARS-CoV-2 S-protein in silico using molecular modelling tools.ResultsSeventeen (17) THPs with experience in response to COVID-19 were identified, of whom 92% had more than 10 years of experience in the practice of traditional medicine. Whereas 43 medical plants were identified and documented, only seven plants, prescribed consistently by all THPs were investigated further. Phytochemical analysis on GC-MS identified compounds belonging to different chemical classes: terpenes, alkanes, alkene, alcohols, acridone, pyrazine, and carboxylic acid esters. Molecular modelling revealed the S-protein to possess multiple active sites. The phytochemicals studied showed potential multiple conformers interacting with each of the S-protein active sites.ConclusionOverall, we identified and modelled phytochemicals with the SARS-CoV-2 S-protein and explained their bioactivities as reported by traditional herbalists. The study underscores the beneficial contribution of traditional medicine in settings where access to comprehensive healthcare services for COVID-19 is limited. The identified plants and/or their phytochemicals could be targeted for conservation and future investigations including in-vivo studies targeting different aspects of the virus replication process, followed by the development of drugs with novel mode of action. The phytochemicals can also be screened for activities against other viruses in the Coronaviridae family.https://www.frontiersin.org/articles/10.3389/fntpr.2025.1597609/fullantiviral activitymolecular modelingspike-proteinhuman ACE-2COVID-19medicinal plants
spellingShingle Trizah K. Milugo
Trizah K. Milugo
Bethwell Owuor
Patrick W. Okanya
Kennedy Chepukosi
George F. Obiero
Natural compounds from ethno-medicinal plants exhibit multiple binding activities on SARS-CoV-2 spike protein receptor-binding domains
Frontiers in Natural Products
antiviral activity
molecular modeling
spike-protein
human ACE-2
COVID-19
medicinal plants
title Natural compounds from ethno-medicinal plants exhibit multiple binding activities on SARS-CoV-2 spike protein receptor-binding domains
title_full Natural compounds from ethno-medicinal plants exhibit multiple binding activities on SARS-CoV-2 spike protein receptor-binding domains
title_fullStr Natural compounds from ethno-medicinal plants exhibit multiple binding activities on SARS-CoV-2 spike protein receptor-binding domains
title_full_unstemmed Natural compounds from ethno-medicinal plants exhibit multiple binding activities on SARS-CoV-2 spike protein receptor-binding domains
title_short Natural compounds from ethno-medicinal plants exhibit multiple binding activities on SARS-CoV-2 spike protein receptor-binding domains
title_sort natural compounds from ethno medicinal plants exhibit multiple binding activities on sars cov 2 spike protein receptor binding domains
topic antiviral activity
molecular modeling
spike-protein
human ACE-2
COVID-19
medicinal plants
url https://www.frontiersin.org/articles/10.3389/fntpr.2025.1597609/full
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