Therapeutic strategies for COVID-19: progress and lessons learned

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(6), P. 449 - 475

Published: April 19, 2023

Language: Английский

---

The research progress of SARS-CoV-2 main protease inhibitors from 2020 to 2022

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 257, P. 115491 - 115491

Published: May 22, 2023

Language: Английский

---

Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 260, P. 115772 - 115772

Published: Aug. 28, 2023

Language: Английский

---

Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(4), P. 2663 - 2680

Published: Feb. 9, 2023

Nirmatrelvir (PF-07321332) is a nitrile-bearing small-molecule inhibitor that, in combination with ritonavir, used to treat infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). interrupts the viral life cycle inhibiting SARS-CoV-2 main protease (Mpro), which essential for processing polyproteins into functional nonstructural proteins. We report studies reveal that derivatives of nirmatrelvir and other Mpro inhibitors nonactivated terminal alkyne group positioned similarly electrophilic nitrile can efficiently inhibit isolated replication cells. Mass spectrometric crystallographic evidence shows apparent irreversible covalent reactions active site cysteine (Cys145), while analogous nitriles react reversibly. The results highlight potential inhibition nucleophilic proteases alkynes, which, contrast nitriles, be functionalized at their position optimize selectivity, as well pharmacodynamic pharmacokinetic properties.

Language: Английский

---

COVID-19 therapeutics: Small-molecule drug development targeting SARS-CoV-2 main protease

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(6), P. 103579 - 103579

Published: April 5, 2023

Language: Английский

---

Structural biology of SARS-CoV-2 Mpro and drug discovery

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 82, P. 102667 - 102667

Published: Aug. 4, 2023

Language: Английский

---

Cyclic β2,3-amino acids improve the serum stability of macrocyclic peptide inhibitors targeting the SARS-CoV-2 main protease

Bulletin of the Chemical Society of Japan, Journal Year: 2024, Volume and Issue: 97(5)

Published: March 6, 2024

Abstract Due to their constrained conformations, cyclic β2,3-amino acids (cβAA) are key building blocks that can fold peptides into compact and rigid structures, improving peptidase resistance binding affinity target proteins, due conformations. Although the translation efficiency of cβAAs is generally low, our engineered tRNA, referred as tRNAPro1E2, enabled efficient incorporation peptide libraries using flexible in vitro (FIT) system. Here we report on design application a macrocyclic library incorporating 3 kinds cβAAs: (1R,2S)-2-aminocyclopentane carboxylic acid (β1), (1S,2S)-2-aminocyclohexane (β2), (1R,2R)-2-aminocyclopentane acid. This was applied an selection against SARS-CoV-2 main protease (Mpro). The resultant peptides, BM3 BM7, bearing one β2 two β1, exhibited potent inhibitory activities with IC50 values 40 20 nM, respectively. BM7 also showed remarkable serum stability half-lives 48 >168 h, Notably, BM3A BM7A, wherein were substituted alanine, lost Mpro displayed substantially shorter half-lives. observation underscores significant contribution cβAA activity peptides. Overall, results highlight potential generating highly stable drug-like properties.

Language: Английский

---

On the origins of SARS-CoV-2 main protease inhibitors

RSC Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 15(1), P. 81 - 118

Published: Oct. 13, 2023

In order to address the world-wide health challenge caused by COVID-19 pandemic, 3CL protease/SARS-CoV-2 main protease (SARS-CoV-2-M

Language: Английский

---

Nanozymes with Modulable Inhibition Transfer Pathways for Thiol and Cell Identification

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

The elementary mechanism and site studies of nanozyme-based inhibition reactions are ambiguous urgently require advanced nanozymes as mediators to elucidate the effect. To this end, we develop a class featuring single Cu–N catalytic configurations B–O sites binding on porous nitrogen-doped carbon substrate (B6/CuSA) for inducing modulable transfer at atomic level. full redistribution electrons across sites, induced by incorporation, yields B6/CuSA with enhanced peroxidase-like activity versus CuSA. More importantly, CuSA features in cysteine expresses competitive through coordination bonds, an constant 0.048 mM. Benefiting from way nanozymes, possesses mixed approaches noncovalent bonds delivers record-mixed interaction 0.054 mM noncompetitive 0.71 Based CuSA, multichannel sensor array accomplishes detection various cancer cells, normal thiols. design principle work is endowed guidelines preliminary evaluation massive potential thiols, cell discrimination, disease prediction.

Language: Английский

---

Design, Synthesis, and Antiviral Activity of Fragmented-Lapatinib Aminoquinazoline Analogs towards SARS-CoV-2 Inhibition

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117303 - 117303

Published: Jan. 1, 2025

Language: Английский

---