Host directed therapies: COVID-19 and beyond
- PMID: 34870156
- PMCID: PMC8464038
- DOI: 10.1016/j.crphar.2021.100058
Host directed therapies: COVID-19 and beyond
Abstract
The global spread of SARS-CoV-2 has necessitated the development of novel, safe and effective therapeutic agents against this virus to stop the pandemic, however the development of novel antivirals may take years, hence, the best alternative available, is to repurpose the existing antiviral drugs with known safety profile in humans. After more than one year into this pandemic, global efforts have yielded the fruits and with the launch of many vaccines in the market, the world is inching towards the end of this pandemic, nonetheless, future pandemics of this magnitude or even greater cannot be denied. The preparedness against viruses of unknown origin should be maintained and the broad-spectrum antivirals with activity against range of viruses should be developed to curb future viral pandemics. The majority of antivirals developed till date are pathogen specific agents, which target critical viral pathways and lack broad spectrum activity required to target wide range of viruses. The surge in drug resistance among pathogens has rendered a compelling need to shift our focus towards host directed factors in the treatment of infectious diseases. This gains special relevance in the case of viral infections, where the pathogen encodes a handful of genes and predominantly depends on host factors for their propagation and persistence. Therefore, future antiviral drug development should focus more on targeting molecules of host pathways that are often hijacked by many viruses. Such cellular proteins of host pathways offer attractive targets for the development of broad-spectrum anticipatory antivirals. In the present article, we have reviewed the host directed therapies (HDTs) effective against viral infections with a special focus on COVID-19. This article also discusses the strategies involved in identifying novel host targets and subsequent development of broad spectrum HDTs.
Keywords: COVID-19; Host directed therapy; Human coronavirus; SARS-CoV-2.
© 2021 The Authors.
Conflict of interest statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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References
-
- Backer V., Sjobring U., Sonne J., Weiss A., Hostrup M., Johansen H.K., Becker V., Sonne D.P., Balchen T., Jellingso M., Sommer M.O.A. A randomized, double-blind, placebo-controlled phase 1 trial of inhaled and intranasal niclosamide: a broad spectrum antiviral candidate for treatment of COVID-19. The Lancet regional health. Europe. 2021;4:100084. - PMC - PubMed
-
- Banerji V., Frumm S.M., Ross K.N., Li L.S., Schinzel A.C., Hahn C.K., Kakoza R.M., Chow K.T., Ross L., Alexe G., Tolliday N., Inguilizian H., Galinsky I., Stone R.M., DeAngelo D.J., Roti G., Aster J.C., Hahn W.C., Kung A.L., Stegmaier K. The intersection of genetic and chemical genomic screens identifies GSK-3α as a target in human acute myeloid leukemia. J. Clin. Invest. 2012;122:935–947. - PMC - PubMed
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