Human host factors

Human host factors refer to the broad array of endogenous cellular components, including proteins, lipids, and glycans, that are exploited by pathogens such as viruses, bacteria, and parasites to facilitate their entry, replication, and dissemination within a host (Nature Reviews Drug Discovery, 2018). Unlike traditional anti-infectives that target pathogen-specific proteins, host-directed therapies (HDTs) target these human factors to disrupt the pathogen's life cycle or to modulate the host's inflammatory response (Frontiers in Immunology, 2020). This approach is advantageous because host factors are less prone to the rapid mutations that lead to drug resistance in pathogens. However, because many host factors perform essential physiological roles, drugs targeting them must be carefully designed to avoid significant toxicity or interference with normal cellular homeostasis (PubMed: 32555371). Examples of targeted host factors include the CCR5 co-receptor for HIV treatment and the TMPRSS2 protease for potential COVID-19 intervention (Science, 2020). Identifying specific host factors through CRISPR screens and proteomics has become a cornerstone of modern infectious disease research (Nature Communications, 2019).

Other names

Host dependency factorsHost cell factorsProviral factorsHost-pathogen interaction factorsHost-directed therapy targets

Host-directed therapy involves the modulation of endogenous host cellular machinery, such as receptors or signaling pathways, to inhibit pathogen entry, replication, or assembly, or to enhance the host's innate immune defenses (Nature Reviews Drug Discovery, 2018).