Towards Host Cell-Targeting Therapies to Treat Dengue Virus Infections

Dengue virus (DENV), a member of the genus Flavivirus in the family Flaviviridae, is the causative agent of the major human viral infection transmitted by mosquitoes in the world with about 390 million annual infections. Recently, a tetravalent vaccine has been licensed for use in highly endemic countries but protective efficacy is not complete and equivalent against the four DENV serotypes. Specific therapeutics is not available at present and treatment is limited to symptomatic supportive care. The reliance of DENV on several host processes and molecules for productive infection highlights the targeting of a cellular factor as an attractive antiviral approach. Since many host requirements are shared by different pathogenic flaviviruses, like Zika virus, West Nile virus, yellow fever virus, Japanese encephalitis virus, tick-borne encephalitis virus, this strategy may provide a wide range effective inhibitory agent and also reduce the possible emergence of antiviral resistant variants. In fact, the few drugs just evaluated or in evaluation at this moment in clinical trials include the host cell-directed compounds chloroquine, lovastatin, prednisolone and celgosivir. This review focuses on the antiviral potential of host cell factors directly participating in the viral cycle of infection as well as those ones involved in the innate antiviral response triggered to restrict and control viral dissemination and pathogenesis.

Keywords: Antiviral, Dengue virus, Endocytosis, Flavivirus, Host target, Innate response, Interferon, Kinases, Lipid metabolism, Nucleotide metabolism, Protein processing, Receptors, Restriction factors, Translation, Ubiquitin proteasome pathway, Unfolded protein response.