Key result
Targeting host dependency factors promises a higher genetic barrier to resistance vs direct-acting antivirals.
Why the study?
The high mutation rates of RNA viruses undermine the effectiveness of direct-acting antivirals and facilitate drug resistance, prompting interest in targeting conserved host dependency factors.
Targeting host dependency factors represents a promising broad-spectrum antiviral strategy with a higher barrier to resistance against RNA viruses.
Supports host-targeted antivirals as research priority; leaves open clinical translation pending prospective trials.
RNA viruses, such as SARS-CoV-2 and influenza, pose a persistent threat to global public health. Their high mutation rates undermine the effectiveness of conventional direct-acting antivirals (DAAs) and facilitate drug resistance. As obligate intracellular parasites, RNA viruses rely extensively on host cellular machinery and metabolic pathways throughout their life cycle. This dependency has prompted a strategic shift in antiviral research—from targeting the mutable virus to targeting relatively conserved host dependency factors (HDFs). In this review, we systematically analyze how RNA viruses exploit HDFs at each stage of infection: utilizing host receptors for entry; remodeling endomembrane systems to establish replication organelles; hijacking transcriptional, translational, and metabolic systems for genome replication and protein synthesis; and co-opting trafficking and budding machinery for assembly and egress. By comparing strategies across diverse RNA viruses, we highlight the broad-spectrum potential of HDF-targeting approaches, which offer a higher genetic barrier to resistance, providing a rational framework for developing host-targeting antiviral therapies.
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Yang et al. (2025) studied this question. Targeting host dependency factors in RNA viruses offers a promising antiviral strategy with a higher genetic barrier to resistance compared to direct-acting antivirals.
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