Modulation of Transcriptomic Signature of the Infected Host: a New Therapeutic Strategy for the Management of Severe Viral Infections? Example of the Flu

Abstract

During the last decades, emergence and re-emergence of viruses were responsible for epidemic and pandemic infectious diseases, with variable degrees of severity. Current preventive strategies are not sufficient at all, and available therapeutic drugs are very limited. Indeed, genetic variations of viruses can impair the efficacy of antiviral compounds by the apparition of resistance. Moreover, current delay needed for de novo development of drugs does not allow a rapid response in case of important epidemic or pandemic events. In this context, new therapeutic approaches are necessary. An innovative concept is to repurpose already marketed compounds that can reverse the host cellular transcriptomic response to the infection. By targeting the host, these molecules exhibit a broad-spectrum activity and are potentially effective even against new emergent strains. This strategy implements the characterization of specific host gene expression profiles, the in silico screening of drugs, and their validation in in vitro and in vivo models, until their evaluation in clinical trials. Here, we will present this approach, with the example of the flu.