Academic Journal
3-Chymotrypsin-like Protease (3CLpro) of SARS-CoV-2: Validation as a Molecular Target, Proposal of a Novel Catalytic Mechanism, and Inhibitors in Preclinical and Clinical Trials
| العنوان: | 3-Chymotrypsin-like Protease (3CLpro) of SARS-CoV-2: Validation as a Molecular Target, Proposal of a Novel Catalytic Mechanism, and Inhibitors in Preclinical and Clinical Trials |
|---|---|
| المؤلفون: | Vitor Martins de Freitas Amorim, Eduardo Pereira Soares, Anielle Salviano de Almeida Ferrari, Davi Gabriel Salustiano Merighi, Robson Francisco de Souza, Cristiane Rodrigues Guzzo, Anacleto Silva de Souza |
| المصدر: | Viruses, Vol 16, Iss 6, p 844 (2024) |
| بيانات النشر: | MDPI AG |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | SARS-CoV-2, 3CLpro, novel mechanism of catalysis, preclinical and clinical trials, triad, Microbiology, QR1-502 |
| الوصف: | Proteases represent common targets in combating infectious diseases, including COVID-19. The 3-chymotrypsin-like protease (3CLpro) is a validated molecular target for COVID-19, and it is key for developing potent and selective inhibitors for inhibiting viral replication of SARS-CoV-2. In this review, we discuss structural relationships and diverse subsites of 3CLpro, shedding light on the pivotal role of dimerization and active site architecture in substrate recognition and catalysis. Our analysis of bioinformatics and other published studies motivated us to investigate a novel catalytic mechanism for the SARS-CoV-2 polyprotein cleavage by 3CLpro, centering on the triad mechanism involving His41-Cys145-Asp187 and its indispensable role in viral replication. Our hypothesis is that Asp187 may participate in modulating the p K a of the His41, in which catalytic histidine may act as an acid and/or a base in the catalytic mechanism. Recognizing Asp187 as a crucial component in the catalytic process underscores its significance as a fundamental pharmacophoric element in drug design. Next, we provide an overview of both covalent and non-covalent inhibitors, elucidating advancements in drug development observed in preclinical and clinical trials. By highlighting various chemical classes and their pharmacokinetic profiles, our review aims to guide future research directions toward the development of highly selective inhibitors, underscore the significance of 3CLpro as a validated therapeutic target, and propel the progression of drug candidates through preclinical and clinical phases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1999-4915 |
| Relation: | https://www.mdpi.com/1999-4915/16/6/844; https://doaj.org/toc/1999-4915; https://doaj.org/article/609c5f7129494b0c86459b5ef37c3585 |
| DOI: | 10.3390/v16060844 |
| الاتاحة: | https://doi.org/10.3390/v16060844 https://doaj.org/article/609c5f7129494b0c86459b5ef37c3585 |
| رقم الانضمام: | edsbas.877C4EE3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19994915 |
|---|---|
| DOI: | 10.3390/v16060844 |