Viral envelope–host cell membrane fusion

Viral envelope–host cell membrane fusion is a biophysical process essential to the infection cycle of enveloped viruses, wherein the lipid bilayer envelope of a virus merges with that of a host cell, enabling entry of the viral genome into the cell[1][2][5][9]. This fusion process is mediated by specialized viral fusion proteins (or fusogens), typically viral surface glycoproteins (e.g., influenza virus HA, HIV gp41/gp120, coronavirus Spike protein), which undergo large conformational rearrangements upon recognition of host cell receptors or after environmental triggers like low pH in endosomes[1][2][6][7]. Viral fusion proteins fall into structural classes (I, II, III), each with distinct mechanisms but converging on a universal strategy: reshaping to bring viral and cellular membranes into close apposition, overcoming the energetic barrier to membrane joining and pore formation[2][4][5][6]. This process is targeted therapeutically by a range of antiviral drugs that interfere with protein-protein interactions, protein conformational changes, or upstream processes such as viral attachment and endocytosis[8][9]. However, "Viral envelope–host cell membrane fusion" is a process, not a single defined molecular target or protein; therapeutically, drugs target the viral fusion proteins or their interactions, not the fusion event itself[6][8]. Thus, while it is a critical antiviral target pathway, the entry as listed is best mapped to specific viral fusion proteins (e.g., HIV gp41, influenza HA, SARS-CoV-2 Spike) when precise drug-target relationships are needed. Therapeutic challenges include viral diversity in fusion protein sequence/structure, emergence of drug-resistant variants, the need for highly specific inhibitors to avoid host toxicity, and immunogenicity of biologic therapies[6][7]. Biomarkers for patient selection and drug efficacy are largely based on measuring the presence of viral fusion proteins or the host's immune response to them.

Other names

Viral membrane fusionVirus-cell membrane fusionVirus-host membrane fusionEnveloped virus fusion

Inhibition of fusion protein conformational changes, Blocking viral glycoprotein–host receptor interactions, Stabilization of pre-fusion protein states, Inhibition of endosomal acidification