image: The crystal structure of the N-terminal RNA-binding domain of SARS-CoV-2 nucleocapsid protein was determined by X-ray. Compared with other previously reported coronavirus nucleocapsid protein N-terminal domains, the authors have identified a unique potential RNA-binding pocket that can guide the design of novel antiviral drugs targeting SARS-CoV-2.
The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continues to cause human infection and mortality worldwide. Currently, there are no specific viral protein-targeted therapeutics available. 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.
In this article, the authors have determined the 2.7 Å 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 the β-sheet core. Complemented by in vitro binding studies, the authors data provides several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, which could guide the design of novel antiviral agents specifically targeting to SARS-CoV-2.