Development of Chimeric MrNV Virus-like Particles Capable of Binding to SARS-CoV-2-susceptible Cells and Reducing Infection by Pseudovirus Variants

Overview

Journal Sci Rep

Specialty Science

Date 2024 Dec 29

PMID 39732908

Authors

Supawich Boonkua

Orawan Thongsum

Purimpuch Soongnart

Rueangtip Chantunmapitak

Somkid Jaranathummakul

Kitima Srisanga

Somluk Asuvapongpatana

Patompon Wongtrakoongate

Wattana Weerachatyanukul

Atthaboon Watthammawut

Monsicha Somrit

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2, the cause of COVID-19, primarily targets lung tissue, leading to pneumonia and lung injury. The spike protein of this virus binds to the common receptor on susceptible tissues and cells called the angiotensin-converting enzyme-2 (ACE2) of the angiotensin (ANG) system. In this study, we produced chimeric Macrobrachium rosenbergii nodavirus virus-like particles, presenting a short peptide ligand (ACE2tp), based on angiotensin-II (ANG II), on their outer surfaces to allow them to specifically bind to ACE2-overexpressing cells called ACE2tp-MrNV-VLPs. Replacing the ACE2tp at the protruding domains (P-domain) of the MrNV capsid proteins did not affect their normal assembly into icosahedral VLPs. The presentation of the ACE2tp on the P-domains significantly improved the binding and internalization of ACE2tp-MrNV-VLPs to hACE2-overexpressing HEK293T cells in a concentration-dependent manner. Furthermore, ACE2tp-MrNV-VLPs exhibited the ability to block the binding and infection of SARS-CoV-2 pseudovirus variants, including Wuhan, BA.2 Omicron, and Delta subtypes. Our results suggest that chimeric ACE2tp-MrNV-VLPs can serve as a blocking agent against various SARS-CoV-2 mutated variants and could also potentially serve as target-specific nano-containers to carry therapeutic agents to combat SARS-CoV-2 infections in the future.

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