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通过靶向核蛋白开发抗人类和动物冠状病毒疾病疗法的当前概念

Current concepts in the development of therapeutics against human and animal coronavirus diseases by targeting NP.

作者信息

Tseng Yeu-Yang, Liao Guan-Ru, Lien Abigail, Hsu Wei-Li

机构信息

WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

Graduate Institute of Microbiology and Public Health, National Chung Hsing University, Taiwan.

出版信息

Comput Struct Biotechnol J. 2021;19:1072-1080. doi: 10.1016/j.csbj.2021.01.032. Epub 2021 Jan 30.

Abstract

The coronavirus (CoV) infects a broad range of hosts including humans as well as a variety of animals. It has gained overwhelming concerns since the emergence of deadly human coronaviruses (HCoVs), severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, followed by Middle East respiratory syndrome coronavirus (MERS-CoV) in 2015. Very recently, special attention has been paid to the novel coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 due to its high mobility and mortality. As the COVID-19 pandemic continues, despite vast research efforts, the effective pharmaceutical interventions are still not available for clinical uses. Both expanded knowledge on structure insights and the essential function of viral nucleocapsid (N) protein are key basis for the development of novel, and potentially, a broad-spectrum inhibitor against coronavirus diseases. This review aimed to delineate the current research from the perspective of biochemical and structural study in cell-based assays as well as virtual screen approaches to identify N protein antagonists targeting not only HCoVs but also animal CoVs.

摘要

冠状病毒(CoV)可感染包括人类在内的多种宿主以及多种动物。自2003年出现致命的人类冠状病毒(HCoV)——严重急性呼吸综合征冠状病毒(SARS-CoV),随后在2015年出现中东呼吸综合征冠状病毒(MERS-CoV)以来,它引起了人们的极大关注。最近,由于新型冠状病毒SARS-CoV-2引起的2019年新型冠状病毒病(COVID-19)具有高传播性和高致死率,受到了特别关注。随着COVID-19大流行的持续,尽管进行了大量研究,但仍没有有效的药物干预措施可用于临床。对病毒核衣壳(N)蛋白的结构见解和基本功能的深入了解,都是开发新型且可能是广谱冠状病毒疾病抑制剂的关键基础。本综述旨在从基于细胞的分析中的生化和结构研究以及虚拟筛选方法的角度,阐述当前的研究,以鉴定不仅针对人类冠状病毒,而且针对动物冠状病毒的N蛋白拮抗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b92/7892624/cdd81b717136/gr1.jpg

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