Design, synthesis, and biological evaluation of dithiocarbamate derivatives as SARS-CoV-2 Mpro inhibitors DOI

Jin-Qi Peng,

Ya-Qi Xiao,

Jiao Long

и другие.

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2024, Номер 114, С. 130011 - 130011

Опубликована: Окт. 31, 2024

Язык: Английский

Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (Mpro) DOI Creative Commons
Yue Yang,

Yidan Luo,

Chenbo Zhang

и другие.

ACS Omega, Год журнала: 2024, Номер 9(32), С. 34196 - 34219

Опубликована: Авг. 2, 2024

Since 2019, the novel coronavirus (SARS-CoV-2) has caused significant morbidity and millions of deaths worldwide. The Coronavirus Disease 2019 (COVID-19), by SARS-CoV-2 its variants, further highlighted urgent need for development effective therapeutic agents. Currently, highly conserved broad-spectrum nature main proteases (M

Язык: Английский

Процитировано

6
Discovery of The Clinical Candidate S-892216: A Second-Generation of SARS-CoV-2 3CL Protease Inhibitor for Treating COVID-19 DOI Open Access
Yuto Unoh,

Keiichiro Hirai,

Shota Uehara

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Abstract The coronavirus disease 2019 (COVID-19) pandemic crisis has been mitigated by worldwide efforts to develop vaccines and therapeutic drugs. However, there remains concern regarding public health an unmet need for options. Herein, we report the discovery of S-892216 , a second-generation SARS-CoV-2 3C-like protease (3CL pro ) inhibitor, treat COVID-19. is reversible covalent 3CL inhibitor with highly potent antiviral activity EC 50 value 2.48 nM against infected cells. Structure-based design modifier compound 1 revealed that introducing nitrile warhead increased inhibition 180-fold. Subsequent optimization yielded which combined favorable pharmacokinetic profile high off-target selectivity. exhibited diverse variants, no cross-resistance major mutations reducing activities nirmatrelvir ensitrelvir. In SARS-CoV-2-infected mice, inhibited viral replication in lungs similar ensitrelvir, although at 30-fold lower dose.

Язык: Английский

Процитировано

0
In Silico and In Vitro Studies of the Approved Antibiotic Ceftaroline Fosamil and Its Metabolites as Inhibitors of SARS-CoV-2 Replication DOI Creative Commons
Cássia P. Delgado, Pablo A. Nogara, Milene Dias Miranda

и другие.

Viruses, Год журнала: 2025, Номер 17(4), С. 491 - 491

Опубликована: Март 28, 2025

The SARS-CoV-2 proteases Mpro and PLpro are critical targets for antiviral drug development the treatment of COVID-19. 1,2,4-thiadiazole functional group is an inhibitor cysteine proteases, such as papain cathepsins. This chemical moiety also present in ceftaroline fosamil (CF), FDA-approved fifth-generation cephalosporin antibiotic. study investigates interactions between CF, its primary metabolites (M1 dephosphorylated CF M2 opened β-lactam ring) derivatives (protonated M1H M2H), open rings (open-M1H open-M2H) with evaluates CF’s effects on vitro viral replication. In silico analyses (molecular docking molecular dynamics (MD) simulations) demonstrated that potential inhibitors Mpro. Docking analysis indicated majority ligands were more stable than PLpro; however, biochemical preferred target CF. inhibited replication human Calu-3 cell model at submicromolar concentrations when added to culture medium 12 h. Our results suggest should be evaluated a repurposing agent COVID-19, considering not only but other relevant cellular pathways. Additionally, reactivity sulfur warrants further exploration protease inhibitors.

Язык: Английский

Процитировано

0
Assay Development and Validation for Innovative Antiviral Development Targeting the N-Terminal Autoprocessing of SARS-CoV-2 Main Protease Precursors DOI Creative Commons

Liangqun Huang,

Megan Gish,

James Boehlke

и другие.

Viruses, Год журнала: 2024, Номер 16(8), С. 1218 - 1218

Опубликована: Июль 29, 2024

The SARS-CoV-2 main protease (M

Язык: Английский

Процитировано

1
Structure-guided design and photochemical synthesis of new carbamo(dithioperoxo)thioates with improved potencies to SARS-CoV-2 3CLpro DOI
Dehang Yin, Jie Xin,

Shizhao Chen

и другие.

Bioorganic & Medicinal Chemistry, Год журнала: 2024, Номер 114, С. 117940 - 117940

Опубликована: Окт. 11, 2024

Язык: Английский

Процитировано

1
Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 Mpro from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants DOI
Xu Wang, Dimitar Gotchev, Kristi Fan

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(21), С. 19623 - 19667

Опубликована: Окт. 25, 2024

The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. main protease (M

Язык: Английский

Процитировано

0
Design, synthesis, and biological evaluation of dithiocarbamate derivatives as SARS-CoV-2 Mpro inhibitors DOI

Jin-Qi Peng,

Ya-Qi Xiao,

Jiao Long

и другие.

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2024, Номер 114, С. 130011 - 130011

Опубликована: Окт. 31, 2024

Язык: Английский

Процитировано

0