Chemically Modified Bovine β-Lactoglobulin as a Broad-Spectrum Influenza Virus Entry Inhibitor with the Potential to Combat Influenza Outbreaks.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Subject Terms:
      COVID-19* ; HIV Fusion Inhibitors* ; Influenza A Virus, H1N1 Subtype* ; Influenza A Virus, H7N9 Subtype* ; Influenza Vaccines* ; Influenza, Human* ; Orthomyxoviridae Infections*/prevention & control; Animals ; Antibodies, Viral ; Cattle ; Disease Outbreaks ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; Humans ; Influenza A Virus, H3N2 Subtype ; Lactoglobulins/pharmacology ; Mice ; N-Acetylneuraminic Acid ; SARS-CoV-2
    • Abstract:
      Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine β-lactoglobulin (3HP-β-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human papillomavirus (HPV) infections. Here, we show its efficacy in potently inhibiting infection by divergent influenza A and B viruses. Mechanistic studies suggest that 3HP-β-LG binds, possibly through its negatively charged residues, to the receptor-binding domain in the hemagglutinin 1 (HA1) subunit in the HA of the influenza virus, thus inhibiting the attachment of the HA to sialic acid on host cells. The intranasal administration of 3HP-β-LG led to the protection of mice against challenges by influenza A(H1N1)/PR8, A(H3N2), and A(H7N9) viruses. Furthermore, 3HP-β-LG is highly stable when stored at 50 °C for 30 days and it shows excellent safety in vitro and in vivo. Collectively, our findings suggest that 3HP-β-LG could be successfully repurposed as an intranasal prophylactic agent to prevent influenza virus infections during influenza outbreaks.
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    • Contributed Indexing:
      Keywords: bovine β-lactoglobulin; broad-spectrum; chemical modification; influenza virus; prevention; viral entry inhibitor
    • Accession Number:
      0 (Antibodies, Viral)
      0 (HIV Fusion Inhibitors)
      0 (Hemagglutinin Glycoproteins, Influenza Virus)
      0 (Hemagglutinins)
      0 (Influenza Vaccines)
      0 (Lactoglobulins)
      GZP2782OP0 (N-Acetylneuraminic Acid)
    • Publication Date:
      Date Created: 20220923 Date Completed: 20220926 Latest Revision: 20221005
    • Publication Date:
      20240829
    • Accession Number:
      PMC9506557
    • Accession Number:
      10.3390/v14092055
    • Accession Number:
      36146861