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.
Keywords: bovine β-lactoglobulin; broad-spectrum; chemical modification; influenza virus; prevention; viral entry inhibitor.
【저자키워드】 prevention, Influenza virus, chemical modification, broad-spectrum, viral entry inhibitor., bovine β-lactoglobulin, 【초록키워드】 viruses, SARS-CoV-2, HIV, Efficacy, coronavirus, Influenza, Infection, influenza A virus, in vitro, Prophylactic, influenza A, viral entry, Outbreaks, infections, outbreak, mice, bovine, in vivo, inhibitor, Human immunodeficiency virus, intranasal, administration, HPV, influenza vaccines, host cells, sialic acid, human papillomavirus, acute respiratory syndrome, subunit, highly pathogenic, Prevent, effective, binds, lack, the receptor-binding domain, inhibiting, charged residues, 【제목키워드】 combat, Potential,