Inhibition of influenza A virus and SARS-CoV-2 infection or co-infection by griffithsin and griffithsin-based bivalent entry inhibitor

Cao, Najing; Cai, Yanxing; Huang, Xin

doi:10.1128/mbio.00741-24

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BioAcyl Corp

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Cao, N., Cai, Y., & Huang, X. Inhibition of influenza a virus and sars-cov-2 infection or co-infection by griffithsin and griffithsin-based bivalent entry inhibitor. mBio, e00741–24.
Added by: Dr. Enrique Feoli (10/04/2024, 17:33) Last edited by: Dr. Enrique Feoli (10/04/2024, 17:45)

Resource type: Journal Article
Published
DOI: 10.1128/mbio.00741-24
BibTeX citation key: Cao
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Categories: BioAcyl Corp
Subcategories: COVID-19
Keywords: ,
Creators: Cai, Cao, Huang
Collection: mBio

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Abstract

Influenza and COVID-19 are highly contagious respiratory illnesses caused by the influenza A virus (IAV) and SARS-CoV-2, respectively. IAV and SARS-CoV-2 co-infection exacerbates damage to lung tissue and leads to more severe clinical symptoms, thus calling for the development of broad-spectrum antivirals for combating IAV and SARS-CoV-2 infection or co-infection. Here we found that griffithsin (GRFT), a carbohydrate-binding protein, and GL25E, a recombinant protein consisting of GRFT, a 25 amino acid linker, and EK1, a broad-spectrum coronavirus inhibitor, could effectively inhibit IAV and SARS-CoV-2 infection and co-infection by targeting glycans on HA of IAV and spike (S) protein of SARS-CoV-2. GL25E is more effective than GRFT because GL25E can also interact with the HR1 domain in SARS-CoV-2 S protein. Furthermore, GL25E possesses favorable safety and stability profiles, suggesting that it is a promising candidate for development as a drug to prevent and treat IAV and SARS-CoV-2 infection or co-infection.

Schematic illustration of the mechanism by which GRFT and GL25E inhibit mono- or co-infection of IAV and SARS-CoV-2. GRFT or GRFT part in GL25E binds to the glycans on HA1 of IAV, thereby inhibiting IAV entry into the host cell. GL25E inhibits SARS-CoV-2 infection by binding via its GRFT part to glycans on S1 subunit of SARS-CoV-2 S protein and interacting via its EK1 part with HR1 domain in S2 subunit of SARS-CoV-2 S protein. GRFT (PDB code: 7RID).