Peng Gong

TL;DR: The molecular basis of SARS-CoV-2 RNA replication is examined by determining the cryo-EM structures of the stalled pre-/post- translocated polymerase complexes and the inhibition mechanisms of the triphosphate metabolite of remdesivir are investigated through structural and kinetic analyses.

TL;DR: The structures indicate that RdRPs use a fully prepositioned templating base for nucleotide recognition and close their active sites for catalysis using a novel structural rearrangement in the palm domain, and suggest that translocation by RDRPs may not be directly linked to the conformational changes responsible for active site closure and reopening.

TL;DR: The first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus is reported, which completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase.

TL;DR: The results show that, although mutator strains are sufficiently fit when grown in large population size, their fitness is greatly impacted when subjected to severe bottlenecking, which would occur during in vivo infection.

TL;DR: Seven RdRP elongation complex structures derived from a crystal lattice that allows three NAC events suggested a key order of events in initial NTP binding and NTP-induced active site closure and revealed a bona fide translocation intermediate featuring asymmetric movement of the template–product duplex.