Characterization of cellular signatures of viral infections to identify compounds with new antiviral indications against paramixoviruses
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are paramyxoviruses associated with acute respiratory tract infections. RSV and HMPV account, respectively, for 40-50% and 5-15% of allrespiratory infections requiring hospitalization in children. To date, there are no approved antivirals or vaccines and new innovative strategies are thus needed for treating these viral infections. This research projectaims at characterizing the cellular transcriptomic signatures of RSV and HMPV in order to identify, through in silico screening of drug databases, broad-spectrum antiviral molecules targeting signaling and metabolicpathways instead of viral molecular determinants. We hypothesize that during an infection, the variations of genomic expression reflect a cellular state favorable to viral replication.
Therefore, we postulate that molecules associated with the reverse cellular transcriptomic signature could induce a cellular state unfavorable to this infection. Our collaborator, Dr Manuel Rosa-Calatrava in Lyon, France, made the proof-of-concept of this strategy by determining the cellular transcriptomic signature of influenza A virus infection and performing in silico screening of available public databases for molecules associated with a cellular stateunfavorable to this infection. Five molecules were selected and characterized for their antiviral properties and their use as a second indication against influenza viruses was patented. Moreover, a clinical study that aimedat evaluating the efficacy of these molecules in influenza-infected patients is ongoing. This project is part of a global drug repositioning effort. This molecule identification strategy targeting cellular pathways is well-adapted to the acute pathogenesis of human respiratory viruses.