Host factors mediating SARS-CoV-2 replication (HDFs)

Host factors mediating SARS-CoV-2 replication refer to the collective set of human cellular proteins and pathways that the SARS-CoV-2 virus hijacks to facilitate its life cycle, including attachment, entry, genome replication, and egress [1, 4]. This group includes the primary entry receptor Angiotensin-converting enzyme 2 (ACE2) and the priming protease Transmembrane protease, serine 2 (TMPRSS2), as well as intracellular factors like the Sigma-1 receptor, PIKfyve kinase, and Dihydroorotate dehydrogenase (DHODH) [1, 2, 4]. Targeting these host-side components is a therapeutic strategy aimed at creating a high genetic barrier to viral resistance, as host proteins do not mutate as rapidly as the viral genome [1, 5]. Drugs such as camostat mesylate, fluvoxamine, and various kinase inhibitors have been investigated for their ability to disrupt these host-virus interactions [1, 4]. However, the primary challenge in targeting host factors is achieving therapeutic efficacy without causing significant toxicity by interfering with the proteins' normal biological functions in the human body [4, 5]. This approach is particularly valuable for developing broad-spectrum antivirals that may remain effective against emerging variants of concern [2, 5].

Other names

Host dependency factorsSARS-CoV-2 host interactomeProviral host factorsHuman-SARS-CoV-2 protein-protein interactions

Host-directed antiviral therapy (HDT) involves the pharmacological modulation of cellular proteins required for the viral life cycle, such as blocking receptor binding (ACE2), inhibiting proteolytic priming (TMPRSS2, Furin), or disrupting intracellular trafficking and replication complexes (PIKfyve, DHODH) [1, 4, 5].