Structure and Function of N-Terminal Zinc Finger Domain of SARS-CoV-2 NSP2

Abstract

SARS-CoV-2 has become a global pandemic threatening human health and safety. It is urgent to find effective therapeutic agents and targets with the continuous emergence of novel mutant strains. The knowledge of the molecular basis and pathogenesis of SARS-CoV-2 in host cells requires to be understood comprehensively. The unknown structure and function of nsp2 have hindered our understanding of its role in SARS-CoV-2 infection. Here, we report the crystal structure of the N-terminal of SARS-CoV-2 nsp2 to a high resolution of 1.96 Å. This novel structure contains three zinc fingers, belonging to the C2H2, C4, and C2HC types, respectively. Structure analysis suggests that nsp2 may be involved in binding nucleic acids and regulating intracellular signaling pathways. The binding to single or double-stranded nucleic acids was mainly through the large positively charged region on the surface of nsp2, and K111, K112, K113 were key residues. Our findings lay the foundation for a better understanding of the relationship between structure and function for nsp2. It is helpful to make full use of nsp2 as further research and development of antiviral targets and drug design. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00431-6.

In silico anti-SARS-CoV-2 activities of five-membered heterocycle-substituted benzimidazoles

“…Herein for carrying the docking analysis PDB ID: 7JLT was selected. In case of NSP2, PDB ID: 7EXM was selected because a x-ray crystallographer [37] suggested that Lys111, Lys112, Lys113 were key residues which are required for interacting with nucleic acid and further and regulating intracellular signaling pathways. Based on Ma and co-workers study, these three positively charged residues were considered for grid generation and molecular docking [37] .…”

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“…The N-terminus of Nsp2 (residues 1 to 276) consists of ten α-helices, fourteen β-strands, and three classic zinc-finger (ZnF) structures: C2H2 ZnF, C4 ZnF, and C2HC ZnF. 145 The residual structure of Nsp2 (residues 277–635) is relatively simple. Its carbon terminus consists of only 14 β-strands, some of which form highly disordered loops, and one 3 10 helix.…”

“…The middle region contains three β-strands and nine α-helices. The Nsp2 protein binds nucleic acids nonspecifically, 141 , 145 with the binding site being either ZnFs 141 or the positively charged region on the surface of Nsp2; 145 the specific identity of the binding site is controversial.…”

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“…Can participate in the binding of nucleic acids and the regulation of intracellular signaling pathways [159]. Participates in the processes of viral replication [160].…”