Effect of Molidustat on organotypic cultures of hamster cerebellum
Airborne RNA viruses from the Paramyxoviridae family include major human pathogens, in particular measles virus (MeV) and Nipah virus (NiV), which is on the blueprint list of WHO due to its high lethality rate and critical risk of emergence. Although an effective vaccine provides protection against MeV, this is not the case for NiV. Besides, there is no cure to treat MeV- or NiV-infected patients despite the risk of developing acute respiratory infections and lethal encephalitis. To identify host-targeting antivirals against these viruses, a library of metabolic modulators has been screened against MeV. Results showed that Molidustat, Daprodustat and Roxadustat, three pharmacological inducers of hypoxia-inducible factors (HIFs), have inhibitory effects on MeV infection both in vitro and ex vivo in organotypic cultures of hamster cerebellum. In addition, we showed that Molidustat inhibits NiV infection in this ex vivo model. Taken together, our results provide evidence that pharmacological induction of the hypoxia response pathway has inhibitory effect on MeV and NiV, suggesting that HIF-inducing drugs are of potential interest for treating these infections. Overall design: RNAseq profiling of ex vivo organotypic cultures of hamster cerebellum treated for 24h with DMSO alone or Molidustat at 25 microM