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Discovery of First-in-Class PROTAC Degraders of SARS-CoV-2 Main Protease.新型冠状病毒主要蛋白酶的首创蛋白降解靶向嵌合体(PROTAC)降解剂的发现。
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Design of a SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model.设计一种具有抗 SARS-CoV-2 木瓜蛋白酶样蛋白酶活性的抑制剂,在小鼠模型中具有抗病毒疗效。
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Molecular dynamic analyses of the interaction of SARS-CoV-1 or 2 variants with various angiotensin-converting enzyme-2 species.严重急性呼吸综合征冠状病毒1型或2型变体与各种血管紧张素转换酶2亚型相互作用的分子动力学分析
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Atorvastatin Effect on COVID-19 Outcomes: A Propensity Score Matched Study on Hospitalized Patients.阿托伐他汀对新冠病毒病结局的影响:一项针对住院患者的倾向评分匹配研究。
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Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial.来瑞特韦用于治疗未联用利托那韦的轻中度新型冠状病毒肺炎:一项多中心随机、双盲、安慰剂对照3期试验
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从广谱冠状病毒抗病毒药物研发中汲取的经验教训。

Lessons learnt from broad-spectrum coronavirus antiviral drug discovery.

作者信息

Bolinger Andrew A, Li Jun, Xie Xuping, Li Hongmin, Zhou Jia

机构信息

Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA.

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.

出版信息

Expert Opin Drug Discov. 2024 Sep;19(9):1023-1041. doi: 10.1080/17460441.2024.2385598. Epub 2024 Jul 30.

DOI:10.1080/17460441.2024.2385598
PMID:39078037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11390334/
Abstract

INTRODUCTION

Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the most recent SARS-CoV-2 responsible for the COVID-19 pandemic, pose significant threats to human populations over the past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic to severe distress syndromes (ARDS), resulting in high morbidity and mortality.

AREAS COVERED

The accelerated advancements in antiviral drug discovery, spurred by the COVID-19 pandemic, have shed new light on the imperative to develop treatments effective against a broad spectrum of CoVs. This perspective discusses strategies and lessons learnt in targeting viral non-structural proteins, structural proteins, drug repurposing, and combinational approaches for the development of antivirals against CoVs.

EXPERT OPINION

Drawing lessons from the pandemic, it becomes evident that the absence of efficient broad-spectrum antiviral drugs increases the vulnerability of public health systems to the potential onslaught by highly pathogenic CoVs. The rapid and sustained spread of novel CoVs can have devastating consequences without effective and specifically targeted treatments. Prioritizing the effective development of broad-spectrum antivirals is imperative for bolstering the resilience of public health systems and mitigating the potential impact of future highly pathogenic CoVs.

摘要

引言

高致病性冠状病毒(CoV),如严重急性呼吸综合征冠状病毒(SARS-CoV)、中东呼吸综合征冠状病毒(MERS-CoV)以及最近引发COVID-19大流行的严重急性呼吸综合征冠状病毒2(SARS-CoV-2),在过去二十年对人类构成了重大威胁。这些冠状病毒引发了从无症状到严重窘迫综合征(急性呼吸窘迫综合征)等广泛的临床表现,导致高发病率和高死亡率。

涵盖领域

由COVID-19大流行推动的抗病毒药物研发加速进展,为开发针对广泛冠状病毒有效的治疗方法的紧迫性带来了新的启示。本观点讨论了在针对病毒非结构蛋白、结构蛋白、药物重新利用以及开发抗冠状病毒抗病毒药物的联合方法方面的策略和经验教训。

专家意见

从这次大流行中吸取教训可以明显看出,缺乏有效的广谱抗病毒药物会增加公共卫生系统对高致病性冠状病毒潜在冲击的脆弱性。如果没有有效且针对性强的治疗方法,新型冠状病毒的快速持续传播可能会产生毁灭性后果。优先有效开发广谱抗病毒药物对于增强公共卫生系统的复原力和减轻未来高致病性冠状病毒的潜在影响至关重要。

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