Human host factors for viral entry and maturation

Human cellular machinery involved in viral entry and maturation encompasses a diverse array of host proteins, including receptors like Angiotensin-converting enzyme 2 (ACE2) and proteases such as TMPRSS2 and Furin, which are essential for the viral life cycle (Hoffmann et al., 2020, Cell; Molloy et al., 1999, Trends in Cell Biology). These host factors facilitate viral attachment, membrane fusion, and the proteolytic processing of viral polyproteins required for the assembly of infectious virions (Diamond & Kanneganti, 2022, Nature Reviews Immunology). Targeting these host-dependency factors is a key strategy in host-directed therapy, providing a broad-spectrum approach that is less susceptible to viral mutational escape (Kaufmann et al., 2018, Nature Reviews Drug Discovery). Drugs such as Camostat mesylate and Maraviroc target specific components of this machinery to inhibit infections by SARS-CoV-2 and HIV-1, respectively (McKee et al., 2020, British Journal of Pharmacology). However, because these proteins often have critical endogenous roles in human physiology, such as blood pressure regulation or protein homeostasis, therapeutic intervention requires careful management of potential side effects (Glowacka et al., 2011, Journal of Virology). This approach is particularly valuable for emerging viruses where specific antivirals are not yet available. The machinery also includes endosomal pathways and intracellular transport mechanisms that viruses hijack. Understanding the interplay between viral proteins and these host factors is crucial for developing effective countermeasures.

Other names

Host dependency factorsViral entry and processing machineryHost-cell viral entry factorsViral entry receptors and host proteases

Host-directed antiviral mechanisms include the competitive or allosteric inhibition of cell-surface receptors to block viral attachment and the inhibition of host-cell proteases to prevent the cleavage of viral glycoproteins necessary for membrane fusion and the release of viral genetic material into the cytoplasm (Hoffmann et al., 2020, Cell; McKee et al., 2020, British Journal of Pharmacology).