RT Journal Article
SR Electronic
T1 Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in Syrian hamsters
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.28.509903
DO 10.1101/2022.09.28.509903
A1 Rana Abdelnabi
A1 Dirk Jochmans
A1 Kim Donckers
A1 Bettina Trüeb
A1 Nadine Ebert
A1 Birgit Weynand
A1 Volker Thiel
A1 Johan Neyts
YR 2022
UL http://biorxiv.org/content/early/2022/09/28/2022.09.28.509903.abstract
AB The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic target for the treatment of COVID-19. Nirmatrelvir is the only the 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization; other 3Lpro inhibitors are in development. We recently repored on the in vitro selection of a SARS-CoV2 3CLpro (L50F-E166A-L167F; short 3CLprores) virus that is cross-resistant with nirmatrelvir and yet other 3CLpro inhibitors. Here, we demonstrate that the resistant virus replicates efficiently in the lungs of intranassaly infected hamsters and that it causes a lung pathology that is comparable to that caused by the WT virus. Moreover, 3CLprores infected hamsters transmit the virus efficiently to co-housed non-infected contact hamsters. Fortunately, resistance to Nirmatrelvir does not readily develop (in the clinical setting) since the drug has a relatively high barrier to resistance. Yet, as we demonstrate, in case resistant viruses emerge, they may easily spread and impact therapeutic options for others. Therefore, the use of SARS-CoV-2 3CLpro protease inhibitors in combinations with drugs that have a different mechanism of action, may be considered to avoid the development of drug-resistant viruses in the future.Competing Interest StatementThe authors have declared no competing interest.