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 …

[HTML][HTML] 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 …

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 …

[HTML][HTML] 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 …

[HTML][HTML] Potential resistance of SARS-CoV-2 main protease (Mpro) against protease inhibitors: lessons learned from HIV-1 protease

JA Mótyán, M Mahdi, G Hoffka, J Tőzsér - International journal of …, 2022 - mdpi.com
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2
(SARS-CoV-2), has been one of the most devastating pandemics of recent times. The lack 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 …

[HTML][HTML] The P132H mutation in the main protease of Omicron SARS-CoV-2 decreases thermal stability without compromising catalysis or small-molecule drug …

MD Sacco, Y Hu, MV Gongora, F Meilleur, MT Kemp… - Cell research, 2022 - nature.com
Dear Editor, The ongoing SARS-CoV-2 pandemic continues to be a significant threat to
global health. First reported in November 2021, the Omicron variant (B. 1.1. 529) is more …

Evolutionary and structural insights about potential SARS-CoV-2 evasion of nirmatrelvir

KS Yang, SZ Leeuwon, S Xu… - Journal of medicinal …, 2022 - ACS Publications
The US FDA approval of PAXLOVID, a combination therapy of nirmatrelvir and ritonavir has
significantly boosted our morale in fighting the COVID-19 pandemic. Nirmatrelvir is an …

[HTML][HTML] Structural basis of nirmatrelvir and ensitrelvir activity against naturally occurring polymorphisms of the SARS-CoV-2 main protease

GD Noske, E de Souza Silva, MO de Godoy… - Journal of Biological …, 2023 - ASBMB
SARS-CoV-2 is the causative agent of COVID-19. The main viral protease (M pro) is an
attractive target for antivirals. The clinically approved drug nirmatrelvir and the clinical …