B, expression of active WT protease or (C) the Q-1A mutant in the presence of the inhibitors nirmatrelvir (NMV) and ensitrelvir (ENS). preMpro, precursor form of Mpro; Mpro, main protease. The Q-1A mutant, purified using the nickel2+ ion that has been coupled to nitrilotriacetic ...
In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir Nat. Commun., 14 (1) (Jul. 2023), 10.1038/s41467-023-40018-1 Art. no. 1 Google Scholar [135] Hotspot residues and resistance mutations in the nirmatrelvir-binding site of SARS-CoV-2 main protease: Design,...
Such a profile was also observed for ensitrelvir, another clinically relevant Mpro inhibitor. These results shed light on the mechanisms by which SARS-CoV-2 evolves to develop resistance to the current generation of protease inhibitors and provide the basis for the design of next-generation Mpro...
Previous research identified resistance of N142A or N142S variants against nirmatrelvir, GC376, and ensitrelvir [34, 35], which we presumed might be partly due to the improved enzymatic activity and unaffected stability of these Mpro mutants since no loss of interaction was observed. Other ...
Rhonda D. Cardin (Pfizer) for providing us with the solvate form of nirmatrelvir. This project has received funding from the Covid-19-Fund KU Leuven/UZ Leuven and the COVID-19 call of FWO (G0G4820N), the European Union’s Horizon 2020 research and innovation program under grant ...
An isothermal calorimetry assay for determining steady state kinetic and Ensitrelvir inhibition parameters for SARS-CoV-2 3CL-protease Article Open access 31 December 2024 Introduction The novel coronavirus disease 2019 (COVID-19) is an upper and lower acute respiratory tract infection that is caus...
Structural basis for the inhibition of coronaviral main proteases by ensitrelvir Structure, Volume 31, Issue 9, 2023, pp. 1016-1024.e3 Cheng Lin,…, Jian Li View PDF Structural Basis for Coronaviral Main Proteases Inhibition by the 3CLpro Inhibitor GC376 Journal of Molecular Biology, Volume...
Novel Investigational Anti-SARS-CoV-2 Agent Ensitrelvir “S-217622”: A Very Promising Potential Universal Broad-Spectrum Antiviral at the Therapeutic Frontline of Coronavirus Species 2023, ACS Omega Evaluation of a series of nucleoside analogs as effective anticoronaviral-2 drugs against the Omicron...
Since most omicron subvariants have reduced sensitivity to most monoclonal antibody therapies, SARS-CoV-2 resistance to other antivirals including main protease inhibitors such as ensitrelvir is a major public health concern. Here, repeating passages of SARS-CoV-2 in the presence of ensitrelvir ...
The crystal structure reveals that ensitrelvir binds to the active site of SARS-CoV-2 3CLpro too, but it only occupies S1’, S1, and S2 subsites without the covalent link to the catalytic residue C145, distinct from the binding modes of the peptidomimetic inhibitors (Supplementary Fig. 9...