Antiviral drugs have traditionally been developed by directly targeting essential viral components. However, this strategy often fails due to the rapid generation of drug-resistant viruses. Recent genome-wide approaches, such as those employing small interfering RNA (siRNA) or clustered regularly interspaced short palindromic repeats (CRISPR) or those using small molecule chemical inhibitors targeting the cellular “kinome,” have been used successfully to identify cellular factors that can support virus replication. Since some of these cellular factors are critical for virus replication, but are dispensable for the host, they can serve as novel targets for antiviral drug development. In addition, potentiation of immune responses, regulation of cytokine storms, and modulation of epigenetic changes upon virus infections are also feasible approaches to control infections. Because it is less likely that viruses will mutate to replace missing cellular functions, the chance of generating drug-resistant mutants with host-targeted inhibitor approaches is minimized. However, drug resistance against some host-directed agents can, in fact, occur under certain circumstances, such as long-term selection pressure of a host-directed antiviral agent that can allow the virus the opportunity to adapt to use an alternate host factor or to alter its affinity toward the target that confers resistance. This review describes novel approaches for antiviral drug development with a focus on host-directed therapies and the potential mechanisms that may account for the acquisition of antiviral drug resistance against host-directed agents.
Bibliographical noteFunding Information:
This work was supported in part by Science and Engineering Research Board (India) grant no. SB/SO/AS-20/2014 and CRG/004747/2018 to N. Kumar. The funding agency had no role in design, data collection and interpretation, or the decision to submit this work for publication.
© 2020 American Society for Microbiology.
- Antiviral agents
- Drug resistance
- Epigenetic regulation
- Host factors
- Precision medicine
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't