Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir

S Iketani, H Mohri, B Culbertson, SJ Hong, Y Duan… - Nature, 2023 - nature.com
Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been
demonstrated to be clinically useful against COVID-19 (refs.,). However, because SARS …

Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir

Y Duan, H Zhou, X Liu, S Iketani, M Lin, X Zhang… - Nature, 2023 - nature.com
Nirmatrelvir is a specific antiviral drug that targets the main protease (Mpro) of SARS-CoV-2
and has been approved to treat COVID-19,. As an RNA virus characterized by high mutation …

In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir

M Kiso, Y Furusawa, R Uraki, M Imai… - Nature …, 2023 - nature.com
Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is
clinically useful against infection with SARS-CoV-2 including its omicron variants. Since …

Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir

Y Hu, EM Lewandowski, H Tan, X Zhang… - ACS central …, 2023 - ACS Publications
The SARS-CoV-2 main protease (Mpro) is the drug target of Pfizer's oral drug nirmatrelvir.
The emergence of SARS-CoV-2 variants with mutations in Mpro raised the alarm of potential …

Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir

S Ullrich, KB Ekanayake, G Otting, C Nitsche - Bioorganic & Medicinal …, 2022 - Elsevier
The COVID-19 pandemic continues to be a public health threat. Multiple mutations in the
spike protein of emerging variants of SARS-CoV-2 appear to impact on the effectiveness of …

SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376

E Heilmann, F Costacurta, SA Moghadasi… - Science translational …, 2022 - science.org
Protease inhibitors are among the most powerful antiviral drugs. Nirmatrelvir is the first
protease inhibitor specifically developed against the SARS-CoV-2 protease 3CLpro that has …

Global prevalence of SARS-CoV-2 3CL protease mutations associated with nirmatrelvir or ensitrelvir resistance

JD Ip, AWH Chu, WM Chan, RCY Leung… - …, 2023 - thelancet.com
Summary Background Nirmatrelvir-ritonavir (Paxlovid) and ensitrelvir are 3-chymotrypsin-
like cysteine protease (3CL pro) inhibitors which have been approved for the treatment of …

Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment

R Abdelnabi, D Jochmans, K Donckers, B Trüeb… - Nature …, 2023 - nature.com
The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic targets for the
treatment of COVID-19. Nirmatrelvir is the first 3CLpro inhibitor authorized for treatment of …

Hotspot residues and resistance mutations in the nirmatrelvir-binding site of SARS-CoV-2 main protease: Design, identification, and correlation with globally …

AK Padhi, T Tripathi - Biochemical and Biophysical Research …, 2022 - Elsevier
Shortly after the onset of the COVID-19 pandemic, severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) has acquired numerous variations in its intracellular proteins to …

The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir

D Jochmans, C Liu, K Donckers, A Stoycheva… - MBio, 2023 - Am Soc Microbiol
The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle
and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors …