Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors

SA Moghadasi, E Heilmann, AM Khalil, C Nnabuife… - Science …, 2023 - science.org
Vaccines and drugs have helped reduce disease severity and blunt the spread of severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, ongoing virus …

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 …

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 …

Ensitrelvir as a potential treatment for COVID-19

MW McCarthy - Expert Opinion on Pharmacotherapy, 2022 - Taylor & Francis
Introduction First-generation therapeutics have improved clinical outcomes in patients
infected with SARS-CoV-2. However, viral evolution has produced variants and subvariants …

Exploring nanoselenium to tackle mutated SARS-CoV-2 for efficient COVID-19 management

A Singh, P Singh, R Kumar, A Kaushik - Frontiers in Nanotechnology, 2022 - frontiersin.org
Despite ongoing public health measures and increasing vaccination rates, deaths and
disease severity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) …

Dynamical nonequilibrium molecular dynamics simulations identify allosteric sites and positions associated with drug resistance in the SARS-CoV-2 main protease

HTH Chan, ASF Oliveira, CJ Schofield, AJ Mulholland… - Jacs Au, 2023 - ACS Publications
The SARS-CoV-2 main protease (Mpro) plays an essential role in the coronavirus lifecycle
by catalyzing hydrolysis of the viral polyproteins at specific sites. Mpro is the target of drugs …

Large library docking for novel SARS‐CoV‐2 main protease non‐covalent and covalent inhibitors

EA Fink, C Bardine, S Gahbauer, I Singh… - Protein …, 2023 - Wiley Online Library
Antiviral therapeutics to treat SARS‐CoV‐2 are needed to diminish the morbidity of the
ongoing COVID‐19 pandemic. A well‐precedented drug target is the main viral protease …

Structural Basis for Coronaviral Main Proteases Inhibition by the 3CLpro Inhibitor GC376

C Lin, Z Zhu, H Jiang, X Zou, X Zeng, J Wang… - Journal of Molecular …, 2024 - Elsevier
The main protease (M pro) of coronaviruses participates in viral replication, serving as a hot
target for drug design. GC376 is able to effectively inhibit the activity of M pro, which is due to …

Rapid resistance profiling of SARS-CoV-2 protease inhibitors

SA Moghadasi, RG Biswas, DA Harki… - npj Antimicrobials and …, 2023 - nature.com
Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already
exist in clinical SARS-CoV-2 isolates. Here a robust cell-based assay is used to determine …

Orthogonal dual reporter-based gain-of-signal assay for probing SARS-CoV-2 3CL protease activity in living cells: inhibitor identification and mutation investigation

ZC Bei, H Yu, H Wang, Q Li, B Wang… - Emerging Microbes & …, 2023 - Taylor & Francis
ABSTRACT The main protease (3-chymotrypsin-like protease, 3CLpro) of SARS-CoV-2 has
become a focus of anti-coronavirus research. Despite efforts, drug development targeting …