COVID-19患者黏液过度分泌:信号通路调控及相关靶向治疗策略  

Mucus hypersecretion in COVID-19 patients:signaling pathway and related targeted therapies

作　　者：陶斯怡 岳涓 钟贤柯梓 李善妮[1] 夏赞贤 TAO SiYi;YUE Juan;ZHONG XianKeZi;LI ShanNi;XIA ZanXian(School of Life Sciences,Central South University,Changsha 410013,China;Xiangya School of Medicine,Central South University,Changsha 410013,China;Department of Human Biology,Faculty of Arts and Science,University of Toronto,Toronto,ON,M5S 1A1,Canada;Hunan Key Laboratory of Animal Models for Human Diseases,School of Life Sciences,Central South University,Changsha 410013,China)

机构地区：[1]中南大学生命科学学院,长沙410013 [2]中南大学湘雅医学院,长沙410013 [3]Department of Human Biology,Faculty of Arts and Science,University of Toronto,Toronto,ON,M5S 1A1,Canada [4]中南大学生命科学学院,人类重大疾病动物模型研究湖南省重点实验室,长沙410013

出　　处：《中国科学：生命科学》2023年第8期1083-1100,共18页Scientia Sinica(Vitae)

基　　金：国家重点研发计划(批准号:2021YFC2300103);国家自然科学基金(批准号:U21A20384,82072293);湖南省重点研发计划(批准号:2020SK2054);湖南省自然科学基金(批准号:2022JJ30692);中南大学研究生科研创新项目(编号1053320215067)资助。

摘　　要：COVID-19是由SARS-CoV-2引起的全球性大流行疾病,已在世界范围内造成严重影响.被SARS-CoV-2感染后,部分患者会出现黏液分泌过多的症状,从而引起呼吸道阻塞.调控黏液分泌的信号通路相对复杂,尽管黏液过度分泌与COVID-19疾病相关性受到的关注较少,但在临床症状中具有重要地位.目前对COVID-19中气道黏液分泌异常的机制研究有限.本文讨论了SARS-CoV-2对气道黏液的影响以及黏液过度分泌的机制,并初步探讨了靶向几种黏液相关信号通路(STAT,MAPK,NF-κB和EGFR)的治疗策略.此外,本文还基于多通路调控提出联合治疗可能是一种更优的治疗策略,并且围绕PROTAC这一新兴的靶向治疗手段进行了展望.在当前SARS-CoV-2致病力减弱、传染性增强的背景下,本工作对COVID-19临床症状相关研究及治疗具有较好的参考和借鉴价值,有望为COVID-19提供新的干预思路.COVID-19 is a global pandemic caused by SARS-CoV-2.Following SARS-CoV-2 infection,some patients develop symptoms of excessive mucus secretion,which is a contributing factor to airway obstruction.The correlation between mucus hypersecretion and COVID-19 has received less attention at the moment,but it plays an important role in clinical symptoms.However,there is currently limited research into the mechanisms underlying abnormal airway mucus secretion in COVID-19.In this paper,SARS-CoV-2 virus and its effect on airway mucus,as well as the mechanism of mucus hypersecretion are discussed.A brief exploration of therapeutic strategies that target several mucus-related signaling pathways will also be presented.Finally,a combination therapy is proposed as a potentially superior therapeutic strategy based on multiple pathway modulation,and an outlook of PROTAC,which is an emerging targeted therapy approach is also provided.Under the current background of weakening pathogenicity and increasing infectivity of SARS-CoV-2 virus,our work our work is highly informative for the study and treatment of clinical symptoms of COVID-19,with the aim of providing an intervention for COVID-19 target.

关 键 词：COVID-19 SARS-CoV-2 黏液分泌 信号通路 靶向治疗 联合治疗 EGFR 

分 类 号：R563.1[医药卫生—呼吸系统]