Antiviral nucleosides

The Covid-19 drug remdesivir (purple) is incorporated into the new RNA chain during copying of the RNA genome by the viral RNA-dependen RNA polymerase (RdRP). The steric clash introduced by the 1’-cyano group imposes a translocation barrier that suppresses the duplication of the coronavirus genome.

Watch this video about why Remdesivir does not fully stop the Coronavirus
in collaboration with Patrick Cramer, MPI-NAT Göttingen.

G. Kokic, H.S. Hillen, D. Tegunov, C. Dienemann, F. Seitz, J. Schmitzova, L. Farnung, A. Siewert, C. Höbartner, P. Cramer
Mechanism of SARS-CoV-2 polymerase stalling by remdesivir
Nat. Commun. 2021, 12, 279.

Structures of SARS-CoV2 RdRP in complex with chemically synthesized RNA containing site-specific N4-hydroxycytidine (NHC) revealed the mechanism of molnupiravir-induced mutagenesis. The antiviral nucleoside analogue is incorporated into the viral RNA, where it leads to mutations that ultimately prevent the virus from replicating.

Watch this video about the mechanism of molnulpiravir-induced SARS-CoV-2 mutagenesis
in collaboration with Patrick Cramer, MPI-NAT Göttingen.

F. Kabinger, C. Stiller, J. Schmitzová, C. Dienemann, G. Kokic, H.S. Hillen, C. Höbartner, P. Cramer
Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis
Nat. Struct. Mol. Biol.  2021, 28, 740-746.

See also: Molnupiravir: coding for catastrophe