Invité équipe B. Canard: Julien Sourimant, UVSQ Paris-Saclay – “The respiratory syncytial virus RNA polymerase: a vulnerable but puzzling engine”

Résumé

Respiratory syncytial virus (RSV) is the main cause for bronchiolitis and pneumonia in infants. RSV belongs to the Pneumoviridae family of the Mononegavirales (MNV) order that contains many other important human pathogens such as Measles, Ebola and Rabies viruses. As all MNV, RSV fully enwraps its non-segmented negative strand RNA genome by the viral nucleoprotein N, which is then replicated and transcribed by a viral RNA dependent RNA polymerase (RdRP) (L protein) and its cofactor (P protein). The RdRP possesses enzymatic activities that are unique in the infected cells, which makes it an attractive drug target. Through a panel of small molecules inhibitors (nucleoside and non-nucleosides), we will describe different mechanisms by which the RdRP of RSV can be inhibited through a combination of biochemical assays and in-silico modeling based on available partial structural data of the RSV RdRP. This work not only validates the relevance of the RdRP as an attractive therapeutic target against viruses such as RSV, but also emphasizes the necessity to further elucidate the structure of the MNV RdRP to better understand their vulnerabilities.