Host cell surface attachment and entry receptor

Host cell surface attachment and entry receptors are a diverse array of molecules, primarily proteins and glycans, that pathogens exploit to gain access to the interior of a host cell (Maginnis, 2018). These receptors are broadly classified into attachment factors, which facilitate the initial docking of the pathogen to the cell surface, and entry receptors, which trigger the actual internalization process through endocytosis or direct membrane fusion (Marsh & Helenius, 2006). Notable examples include the Angiotensin-converting enzyme 2 (ACE2) used by SARS-CoV-2 and the CD4/CCR5 complex used by HIV-1 (Hoffmann et al., 2020; Wilen et al., 2012). Because these receptors represent the first point of contact between a pathogen and its host, they are prime targets for therapeutic intervention, including small molecule inhibitors and monoclonal antibodies (Tilton & Doms, 2010). However, since many of these molecules have essential physiological roles, such as regulating blood pressure or mediating immune cell trafficking, drug development must ensure that pathogen blockade does not lead to significant host toxicity (Clapham, 2014).

Other names

Viral entry receptorsHost cell receptorsAttachment factorsCell surface entry mediatorsPathogen entry receptors

Drugs targeting these receptors typically act as competitive antagonists or allosteric inhibitors that prevent the binding of pathogen surface proteins to the host cell (Tilton & Doms, 2010). Some agents, such as monoclonal antibodies, may sterically hinder the interaction or induce receptor internalization to reduce surface availability (Wilen et al., 2012). Others, like fusion inhibitors, prevent the conformational changes required for the pathogen to merge its membrane with the host cell membrane (Marsh & Helenius, 2006).