Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

• 作者: Changsheng Zhang Hong Shan Liping Zhang Mei Yang Qiuyue Chen Shoudeng Chen Sisi Kang Suhua He Xiaoxue Chen Yan Yan Zhaoxia Huang Zhechong Zhou Zhongsi Hong Ziliang Zhou
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2020,（7）
• 所属期刊栏目: Original Articles
• 页码范围: 1228-1238
• 页数: 11页
• 语种: 英文

摘要

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths.Currently,there is no specific viral protein-targeted therapeutics.Viral nucleocapsid protein is a potential antiviral drug target,serving multiple critical functions during the viral life cycle.However,the structural information of SARS-CoV-2 nucleocapsid protein remains unclear.Herein,we have determined the 2.7(A) crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein.Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain; the surface electrostatic potential characteristics between them are distinct.Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside theβ-sheet core.Complemented by in vitro binding studies,our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain,guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.