Discovery of Fluorescent Naturally‐Occurring Inhibitor of SARS‐CoV‐2 Main Protease by AIE Fluorescent Probe DOI
Hao Lin, Chong‐Jing Zhang

ChemMedChem, Год журнала: 2024, Номер 19(21)

Опубликована: Июль 8, 2024

Abstract Target‐based high‐throughput screening (HTS) is an efficient way to identify potent drugs. However, the accuracy of HTS could be affected by Pan‐Assay Interference Compounds (PAINS). One reason for generation PAINS that inherent photophysical property screened compounds interfere with typically used assay signals including absorption and fluorescence. Our previous studies indicate fluorescent probe based on fluorophore characteristics aggregation‐induced emission (AIE) provide high HTS, especially natural products. Herein, we report AIE‐based main protease (M pro ) severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). We designed synthesized AIE ZLHG5, which has a site can specifically cleaved M produce light‐up Thanks large Stokes shift (~200 nm), effectively inhibitors. After library products obtained two coumarin‐originated inhibitory activity towards protease. This study provides both useful inhibitors

Язык: Английский

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

Xiaojing Pang,

Wei Xu, Yang Liu

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 257, С. 115491 - 115491

Опубликована: Май 22, 2023

Язык: Английский

Процитировано

62
Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review DOI Creative Commons
Xin Li, Yongcheng Song

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 260, С. 115772 - 115772

Опубликована: Авг. 28, 2023

Язык: Английский

Процитировано

52
Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives DOI Creative Commons
Andrea Citarella, Alessandro Dimasi, Davide Moi

и другие.

Biomolecules, Год журнала: 2023, Номер 13(9), С. 1339 - 1339

Опубликована: Сен. 2, 2023

The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered highly conserved viral target. Disruption catalytic activity Mpro produces detrimental effect on course infection, making this target one most attractive for treatment COVID-19. current success SARS-CoV-2 inhibitor Nirmatrelvir, first oral drug forms COVID-19, has further focused attention researchers important target, search new inhibitors thriving exciting field development antiviral drugs active against related coronaviruses.

Язык: Английский

Процитировано

27
Exploring diverse reactive warheads for the design of SARS-CoV-2 main protease inhibitors DOI Creative Commons
Bin Tan, M. Sacco, Haozhou Tan

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 259, С. 115667 - 115667

Опубликована: Июль 19, 2023

Язык: Английский

Процитировано

20
On the origins of SARS-CoV-2 main protease inhibitors DOI
Yves L. Janin

RSC Medicinal Chemistry, Год журнала: 2023, Номер 15(1), С. 81 - 118

Опубликована: Окт. 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

Язык: Английский

Процитировано

17
Non-peptidic inhibitors targeting SARS-CoV-2 main protease: A review DOI

Ya-Qi Xiao,

Jiao Long, Shuang‐Shuang Zhang

и другие.

Bioorganic Chemistry, Год журнала: 2024, Номер 147, С. 107380 - 107380

Опубликована: Апрель 16, 2024

Язык: Английский

Процитировано

7
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
Design, Synthesis, and Biological Evaluation of Trisubstituted Piperazine Derivatives as Noncovalent Severe Acute Respiratory Syndrome Coronavirus 2 Main Protease Inhibitors with Improved Antiviral Activity and Favorable Druggability DOI
Shenghua Gao,

Letian Song,

Katharina Sylvester

и другие.

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(23), С. 16426 - 16440

Опубликована: Ноя. 22, 2023

The ongoing transmission of SARS-CoV-2 necessitates the development additional potent antiviral agents capable combating current highly infectious variants and future coronaviruses. Here, we present discovery nonpeptide main protease (Mpro) inhibitors with prominent activity improved pharmacokinetic properties. Three series 1,2,4-trisubstituted piperazine derivatives were designed synthesized, optimal GC-78-HCl demonstrated high enzyme–inhibitory potency (IC50 = 0.19 μM) exhibited excellent (EC50 0.40 μM), reaching same level as Nirmatrelvir 0.38 μM). Additionally, displayed activities against various well HCoV-OC43 HCoV-229E, indicating its potential broad-spectrum anticoronaviral activity. Notably, properties somewhat enhanced compared to those lead compound. Furthermore, cocrystal molecular docking elucidated mechanism action. In conclusion, discovered a novel nonpeptidic Mpro inhibitor promising favorable profile.

Язык: Английский

Процитировано

14
Discovery and Mechanism Study of SARS-CoV-2 3C-like Protease Inhibitors with a New Reactive Group DOI
Pengxuan Ren, Hui Li, Tianqing Nie

и другие.

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(17), С. 12266 - 12283

Опубликована: Авг. 18, 2023

3CLpro is an attractive target for the treatment of COVID-19. Using scaffold hopping strategy, we identified a potent inhibitor (3a) that contains thiocyanate moiety as novel warhead can form covalent bond with Cys145 protein. Tandem mass spectrometry (MS/MS) and X-ray crystallography confirmed mechanism formation between 3a protein in its catalytic pocket. Moreover, several analogues compound were designed synthesized. Among them, 3h shows best inhibition IC50 0.322 μM kinact/Ki value 1669.34 M–1 s–1, it exhibits good selectivity against host proteases. Compound 3c inhibits SARS-CoV-2 Vero E6 cells (EC50 = 2.499 μM) low cytotoxicity (CC50 > 200 μM). These studies provide ideas insights to explore develop new inhibitors future.

Язык: Английский

Процитировано

13
Fragment-based drug discovery for disorders of the central nervous system: designing better drugs piece by piece DOI Creative Commons

Bill W. G. L. Chan,

Nicholas B. Lynch, Wendy Tran

и другие.

Frontiers in Chemistry, Год журнала: 2024, Номер 12

Опубликована: Апрель 18, 2024

Fragment-based drug discovery (FBDD) has emerged as a powerful strategy to confront the challenges faced by conventional development approaches, particularly in context of central nervous system (CNS) disorders. FBDD involves screening libraries that comprise thousands small molecular fragments, each no greater than 300 Da size. Unlike generally larger molecules from high-throughput limit customisation, fragments offer more strategic starting point. These are inherently compact, providing strong foundation with good binding affinity for candidates. The minimal elaboration required transition hit into drug-like molecule is not only accelerated, but also it allows precise modifications enhance both their activity and pharmacokinetic properties. This shift towards fragment-centric approach seen commercial success holds considerable promise continued streamlining process. In this review, we highlight how can be integrated CNS process exploration target. Furthermore, provide recent examples where been an integral component programs, enabling improvement properties have previously proven challenging. optimisation provides systematic explore vast chemical space, facilitating design compounds piece capable modulating crucial targets.

Язык: Английский

Процитировано

5