Replacing protruding domains of MrNV virus-like particles with sialic acid binding domains enhances binding to SARS-CoV-2 susceptible cells and reduces pseudovirus infection

Abstract The SARS-CoV-2 virus continues to pose a public health threat due to its ability to rapidly mutate into multiple variants via mutation in its spike (S1/2) proteins. These mutations can lead to viral variants capable of escaping antibody neutralization. The interaction between the SARS-CoV-2...

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Main Authors: Supawich Boonkua, Orawan Thongsum, Rueangtip Chantunmapitak, Purimpuch Soongnart, Somkid Jaranathummakul, Kitima Srisanga, Patompon Wongtrakoongate, Somluk Asuvapongpatana, Wattana Weerachatyanukul, Atthaboon Watthammawut, Monsicha Somrit
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Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10792-7
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author Supawich Boonkua
Orawan Thongsum
Rueangtip Chantunmapitak
Purimpuch Soongnart
Somkid Jaranathummakul
Kitima Srisanga
Patompon Wongtrakoongate
Somluk Asuvapongpatana
Wattana Weerachatyanukul
Atthaboon Watthammawut
Monsicha Somrit
author_facet Supawich Boonkua
Orawan Thongsum
Rueangtip Chantunmapitak
Purimpuch Soongnart
Somkid Jaranathummakul
Kitima Srisanga
Patompon Wongtrakoongate
Somluk Asuvapongpatana
Wattana Weerachatyanukul
Atthaboon Watthammawut
Monsicha Somrit
author_sort Supawich Boonkua
collection DOAJ
description Abstract The SARS-CoV-2 virus continues to pose a public health threat due to its ability to rapidly mutate into multiple variants via mutation in its spike (S1/2) proteins. These mutations can lead to viral variants capable of escaping antibody neutralization. The interaction between the SARS-CoV-2 spike protein and the host ACE2 receptor is influenced by carbohydrate-mediated mechanisms, as the spike is heavily glycosylated with terminal sialic acids, making these sugar moieties attractive targets for therapeutic intervention. We aimed to study the complete replacement of their protrusion domains of Macrobrachium rosenbergii nodavirus capsid protein with the larger ligands in the form of carbohydrate-recognition domain derived from a terminal sialic acid-binding lectin (tsCRD). We produced chimeric virus-like particles MrNV-VLPs to display the tsCRD peptide sequence of the Sambucus Nigra Agglutinin (SNA-I). The tsCRD-MrNV-VLPs maintained their icosahedral structure and increased binding and uptake into ACE2-overexpressing cells. Additionally, these particles exhibited significant blocking capability against various SARS-CoV-2 pseudo-virus variants such as Wuhan, Delta, and Omicron. Our results demonstrated that tsCRD-MrNV-VLPs have the potential to be developed into an effective agent to block and reduce SARS-CoV-2 infection in susceptible cells and present the potential of these VLPs for protective applications.
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id doaj-art-da6c0a3a5f5145c1bf9f2d1058a64c44
institution Kabale University
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publishDate 2025-07-01
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spelling doaj-art-da6c0a3a5f5145c1bf9f2d1058a64c442025-08-20T04:01:52ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-10792-7Replacing protruding domains of MrNV virus-like particles with sialic acid binding domains enhances binding to SARS-CoV-2 susceptible cells and reduces pseudovirus infectionSupawich Boonkua0Orawan Thongsum1Rueangtip Chantunmapitak2Purimpuch Soongnart3Somkid Jaranathummakul4Kitima Srisanga5Patompon Wongtrakoongate6Somluk Asuvapongpatana7Wattana Weerachatyanukul8Atthaboon Watthammawut9Monsicha Somrit10Department of Anatomy, Faculty of Science, Mahidol UniversityDepartment of Anatomy, Faculty of Science, Mahidol UniversityDepartment of Anatomy, Faculty of Science, Mahidol UniversityDepartment of Anatomy, Faculty of Science, Mahidol UniversityDepartment of Anatomy, Faculty of Science, Mahidol UniversityDepartment of Biochemistry, Faculty of Science, Mahidol UniversityDepartment of Biochemistry, Faculty of Science, Mahidol UniversityDepartment of Anatomy, Faculty of Science, Mahidol UniversityDepartment of Anatomy, Faculty of Science, Mahidol UniversityCenter for Neuroscience, Faculty of Science, Mahidol UniversityDepartment of Anatomy, Faculty of Science, Mahidol UniversityAbstract The SARS-CoV-2 virus continues to pose a public health threat due to its ability to rapidly mutate into multiple variants via mutation in its spike (S1/2) proteins. These mutations can lead to viral variants capable of escaping antibody neutralization. The interaction between the SARS-CoV-2 spike protein and the host ACE2 receptor is influenced by carbohydrate-mediated mechanisms, as the spike is heavily glycosylated with terminal sialic acids, making these sugar moieties attractive targets for therapeutic intervention. We aimed to study the complete replacement of their protrusion domains of Macrobrachium rosenbergii nodavirus capsid protein with the larger ligands in the form of carbohydrate-recognition domain derived from a terminal sialic acid-binding lectin (tsCRD). We produced chimeric virus-like particles MrNV-VLPs to display the tsCRD peptide sequence of the Sambucus Nigra Agglutinin (SNA-I). The tsCRD-MrNV-VLPs maintained their icosahedral structure and increased binding and uptake into ACE2-overexpressing cells. Additionally, these particles exhibited significant blocking capability against various SARS-CoV-2 pseudo-virus variants such as Wuhan, Delta, and Omicron. Our results demonstrated that tsCRD-MrNV-VLPs have the potential to be developed into an effective agent to block and reduce SARS-CoV-2 infection in susceptible cells and present the potential of these VLPs for protective applications.https://doi.org/10.1038/s41598-025-10792-7Virus-like particles (VLPs)Macrobrachium rosenbergii nodavirus (MrNV)NanotechnologyGenetic modification
spellingShingle Supawich Boonkua
Orawan Thongsum
Rueangtip Chantunmapitak
Purimpuch Soongnart
Somkid Jaranathummakul
Kitima Srisanga
Patompon Wongtrakoongate
Somluk Asuvapongpatana
Wattana Weerachatyanukul
Atthaboon Watthammawut
Monsicha Somrit
Replacing protruding domains of MrNV virus-like particles with sialic acid binding domains enhances binding to SARS-CoV-2 susceptible cells and reduces pseudovirus infection
Scientific Reports
Virus-like particles (VLPs)
Macrobrachium rosenbergii nodavirus (MrNV)
Nanotechnology
Genetic modification
title Replacing protruding domains of MrNV virus-like particles with sialic acid binding domains enhances binding to SARS-CoV-2 susceptible cells and reduces pseudovirus infection
title_full Replacing protruding domains of MrNV virus-like particles with sialic acid binding domains enhances binding to SARS-CoV-2 susceptible cells and reduces pseudovirus infection
title_fullStr Replacing protruding domains of MrNV virus-like particles with sialic acid binding domains enhances binding to SARS-CoV-2 susceptible cells and reduces pseudovirus infection
title_full_unstemmed Replacing protruding domains of MrNV virus-like particles with sialic acid binding domains enhances binding to SARS-CoV-2 susceptible cells and reduces pseudovirus infection
title_short Replacing protruding domains of MrNV virus-like particles with sialic acid binding domains enhances binding to SARS-CoV-2 susceptible cells and reduces pseudovirus infection
title_sort replacing protruding domains of mrnv virus like particles with sialic acid binding domains enhances binding to sars cov 2 susceptible cells and reduces pseudovirus infection
topic Virus-like particles (VLPs)
Macrobrachium rosenbergii nodavirus (MrNV)
Nanotechnology
Genetic modification
url https://doi.org/10.1038/s41598-025-10792-7
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