Structural basis of RNA recognition by the SARS-CoV-2 nucleocapsid phosphoprotein

Dhurvas Chandrasekaran Dinesh; Dominika Chalupska; Jan Silhan; Vaclav Veverka; Evzen Boura

Coronaviruses have the largest known genomes (up to 32 kb) among +RNA viruses, and they encode four structural and sixteen non-structural proteins. The non-structural proteins carry all of the enzymatic activities important for the viral replication, mostly associated with RNA replication. The genome SARS-CoV-2 also encodes an RNA-dependent RNA-polymerase complex (nsp7, nsp8 and nsp12), RNA capping machinery (nsp10, nsp13, nsp14 and 16) and additional enzymes such as proteases (the nsp3 PL pro and the nsp5 3CL pro ) which cleave viral polyproteins and/or impede innate immunity (1) . The four structural proteins together with the viral +RNA genome and the envelope constitute the virion. The matrix (M), small envelope (E), and spike (S) proteins are embedded within the lipid envelope. The fourth structural protein, the nucleocapsid phosphoprotein (N), physically links the envelope to the +RNA genome. It consists of an N-terminal (NTD) and a C-terminal (CTD) domain ( Figure 1 ). Both domains are capable of RNA binding. In addition, the CTD serves as a dimerization domain and binds the matrix protein forming the physical link between the+ RNA genome and the envelope. The SARS N protein has also been shown to modulate the host intracellular machinery and plays regulatory roles during the viral life cycle (2) . In light of the genomic similarities between SARS-CoV and SARS-CoV-2, it is reasonable to expect the N protein to function in a similar way.