Host cell surface receptors and entry factors

Host cell surface receptors and entry factors comprise a broad category of host-encoded proteins and carbohydrates that pathogens exploit to facilitate attachment and internalization into target cells (Maginnis, 2018). These molecules serve as the primary gateway for infection, with viruses often requiring a specific primary receptor for binding and, in many cases, a secondary co-receptor to trigger membrane fusion or endocytosis (Marsh & Helenius, 2006). Notable examples include the CD4 receptor and CCR5/CXCR4 co-receptors for HIV-1, and the Angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 (Shang et al., 2020; Tilton & Doms, 2010). Because these factors are essential for the initiation of the viral life cycle, they are significant targets for the development of entry inhibitors. However, a major challenge in targeting host factors is the potential for toxicity, as many of these receptors perform critical endogenous functions such as immune response modulation, enzymatic activity, or cellular signaling (Baranowski et al., 2001).

Other names

Viral entry receptorsHost entry factorsPathogen attachment factorsCell surface entry mediatorsViral receptors

Entry inhibition via competitive or allosteric antagonism of host receptors, preventing viral attachment, co-receptor engagement, or membrane fusion (Tilton & Doms, 2010).