Bolinger Andrew A, Li Jun, Xie Xuping, Li Hongmin, Zhou Jia
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.
Expert Opin Drug Discov. 2024 Sep;19(9):1023-1041. doi: 10.1080/17460441.2024.2385598. Epub 2024 Jul 30.
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.
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.
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.
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。
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。
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。