期刊
VIRUSES-BASEL
卷 14, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/v14092055
关键词
influenza virus; viral entry inhibitor; broad-spectrum; prevention; chemical modification; bovine beta-lactoglobulin
类别
资金
- National Key Research and Development Program of China [2021YFC2300703]
- National Natural Science Foundation of China [92169112, 82161138002]
- Shanghai Municipal Science and Technology Major Project [ZD2021CY001]
- Natural Science Foundation of Guangdong Province, China [2020A1515010979]
3HP-beta-LG is a broad-spectrum prophylactic agent that can effectively inhibit the infection of divergent influenza A and B viruses, and it shows stability and safety.
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 beta-lactoglobulin (3HP-beta-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-beta-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-beta-LG led to the protection of mice against challenges by influenza A(H1N1)/PR8, A(H3N2), and A(H7N9) viruses. Furthermore, 3HP-beta-LG is highly stable when stored at 50 degrees C for 30 days and it shows excellent safety in vitro and in vivo. Collectively, our findings suggest that 3HP-beta-LG could be successfully repurposed as an intranasal prophylactic agent to prevent influenza virus infections during influenza outbreaks.
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