Host dependency factors (HDFs)

Host dependency factors (HDFs) are a diverse group of host cell proteins, RNAs, and metabolic pathways that pathogens, particularly viruses, hijack to facilitate their entry, genome replication, assembly, and exit from the cell. Unlike viral proteins, which are prone to rapid mutation and drug resistance, HDFs are genetically stable host components, making them attractive targets for 'host-directed therapy' (HDT) to achieve broad-spectrum antiviral activity. Common examples of HDFs include cell surface receptors like CCR5 for HIV or ACE2 for SARS-CoV-2, as well as intracellular enzymes like dihydroorotate dehydrogenase (DHODH) or cyclophilins. While targeting HDFs can provide a high barrier to the development of drug resistance, it also carries the inherent risk of disrupting normal physiological processes, leading to potential toxicity. Consequently, drug development in this space focuses on identifying HDFs that are non-essential for immediate host cell survival or those that have a significant therapeutic window during acute infection.

Other names

Host cell factorsProviral factorsHost-virus interaction proteinsHost-pathogen interaction factors

Host-directed therapy involves inhibiting or modulating endogenous cellular proteins that pathogens exploit to complete their life cycle, thereby preventing infection, replication, or egress.