Viral envelope glycoproteins and host cell surface attachment factors

Viral envelope glycoproteins and host cell surface attachment factors constitute the essential molecular interface required for viruses to infect host cells. Viral glycoproteins, such as the HIV-1 gp120/gp41 complex or the SARS-CoV-2 spike protein, are displayed on the viral envelope and serve as the primary tools for host recognition (https://pubmed.ncbi.nlm.nih.gov/23433395/). These proteins bind to specific host cell surface attachment factors or receptors, such as CD4, CCR5, or ACE2, to initiate the infection process (https://www.nature.com/articles/s41580-020-00318-5). This binding often triggers a cascade of conformational changes that facilitate the fusion of the viral envelope with the host cell membrane or promote endocytosis. Because this step is the first and most critical stage of the viral life cycle, these proteins are high-priority targets for the development of antiviral drugs and vaccines. Therapeutic strategies include the use of small molecules to block receptor binding and monoclonal antibodies to neutralize the viral glycoproteins directly (https://clinicalinfo.hiv.gov/en/glossary/entry-inhibitors).

Other names

Viral entry proteinsViral attachment receptorsViral fusion machineryViral entry factors

Drugs targeting these factors typically act as entry inhibitors, which include attachment inhibitors that block the initial binding of the virus to the host cell, receptor antagonists that bind to host receptors to prevent viral docking, and fusion inhibitors that prevent the viral and host membranes from merging.