Structure of the Respiratory Syncytial Virus Polymerase Complex

Morgan S A Gilman (1) , Cheng Liu (2) , Amy Fung (2) , Ishani Behera (2) , Paul Jordan (2) , Peter Rigaux (3) , Nina Ysebaert (3) , Sergey Tcherniuk (4) , Julien Sourimant (5, 6) , Jean-Francois Eleouet (6) , Priscila Sutto-Ortiz (7) , Etienne Decroly (8) , Dirk Roymans (3) , Zhinan Jin (2) , Jason S Mclellan (1)

1 University of Texas at Austin [Austin]
2 Janssen BioPharma
3 Janssen Infectious Diseases and Vaccines
4 CRBM - Centre de recherche en Biologie cellulaire de Montpellier
5 Université Paris-Saclay
6 INRA - Institut National de la Recherche Agronomique
7 BIP - Bioénergétique et Ingénierie des Protéines
8 AFMB - Architecture et fonction des macromolécules biologiques

Graphical Abstract Highlights d Cryo-EM structure of RSV L bound by tetrameric RSV P solved to 3.2 Å d P tetramer adopts an asymmetric tentacular arrangement when bound to L d L priming loop adopts elongation-compatible state without PRNTase-RdRp separation d Structure rationalizes escape from small-molecule antivirals In Brief Respiratory syncytial virus (RSV) remains a leading cause of bronchiolitis and hospitalization, especially of infants. Gilman et al. present a 3.2-Å cryo-EM structure of the RSV L polymerase in complex with the P phosphoprotein-components of the core viral replication machinery that represent an attractive target for the development of therapeutic agents. Data Resources 6PZK

Keywords: RdRp; PRNTase; MTase; allostery; ALS-8176

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Structural Biology [q-bio.BM]

Morgan S A Gilman, Cheng Liu, Amy Fung, Ishani Behera, Paul Jordan, et al.. Structure of the Respiratory Syncytial Virus Polymerase Complex. Cell, 2019, 179 (1), pp.193-204.e14. ⟨10.1016/j.cell.2019.08.014⟩. ⟨hal-02353778⟩