Host cell entry receptor and attachment factor

Host cell entry receptors and attachment factors represent a broad functional class of cell surface molecules that pathogens, particularly viruses, exploit to initiate infection (Maginnis, 2018, J. Virol.). This category encompasses a wide variety of proteins and carbohydrates, such as ACE2 for SARS-CoV-2 or CCR5 for HIV-1, rather than a single molecular entity. Attachment factors, such as heparan sulfate proteoglycans, facilitate the initial, often low-affinity, recruitment of the pathogen to the cell surface, thereby increasing the local concentration of infectious particles (Marsh & Helenius, 2006, Cell). In contrast, entry receptors are specific molecules that bind the pathogen and trigger essential downstream processes, such as receptor-mediated endocytosis or direct membrane fusion (Hoffmann et al., 2020, Cell). Because these factors are essential for the earliest stages of the viral life cycle, they represent significant therapeutic targets for the development of entry inhibitors. Examples of drugs targeting these host factors include Maraviroc, which blocks the CCR5 coreceptor, and Bulevirtide, which targets the NTCP receptor (Bogomolov et al., 2016, J. Hepatol.). Targeting host factors can potentially offer a higher genetic barrier to viral resistance compared to drugs that target rapidly mutating viral proteins. However, since many of these receptors have vital endogenous roles in signal transduction or immune regulation, therapeutic strategies must be carefully designed to avoid disrupting normal cellular homeostasis (Barre-Sinoussi et al., 2013, Nat. Rev. Microbiol.).

Other names

Viral entry receptorHost cell receptorAttachment factorPathogen entry mediatorCellular entry factorViral attachment factor

Inhibition of pathogen entry by blocking binding sites on host receptors or preventing the conformational changes required for membrane fusion and endocytosis.