The first step in viral infection is the attachment of the virus onto the host cell. This process is mediated by viral fusion proteins, which are expressed on the surface of the virus(1). Examples of these fusion proteins include gp120 of HIV(2), the hemagglutinin glycoprotein (HA) of the influenza virus(3), and most recently, the spike protein of the SARS-CoV-2 virus(4). All three of these examples belong to the family of class I viral membrane fusion proteins(5). Due to their necessary role in viral infection, these proteins are the targets of many antiviral therapeutic strategies which include small molecules and neutralizing antibodies(6).
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