NSP2

General information on NSP2

Non-structural protein 2, also known as nsp2, is a RNA-binding protein that accumulates in cytoplasmic inclusions (viroplasms). Nsp2 is involved in coronavirus (CoVs) genome replication. CoVs are large positive-sense single-stranded RNA genomes enveloped viruses and can affect birds, animals and humans. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus SARS-CoV are both coronavirus strains that cause 2019 Novel Coronavirus disease (COVID-19) and severe acute respiratory syndrome (SARS) respectively. The CoVs genome of both of these strains consists of several open reading frames (ORF). ORF1a and ORF1b genes, produce two polyproteins pp1a and pp1b. These polyproteins help take command over host ribosomes for their own translation process. They are processed by polyproteases and produce 16 non-structural proteins (nsp). PLpro protein cleaves the N-terminus of the replicase polyprotein to release Nsp1, Nsp2 and Nsp3. This step is essential for the viral replication. Nsp2, along with nsp1, are involved in suppressing gene expression.
Compared to other nsp proteins, nsp2 protein, similar to nsp1 protein, varies among different CoVs strains. There are three groups (1, 2 and 3) of COVs based on genome organization and serotype specificity. Different amino acid sequence identity has been observed in these three groups. Non-structural protein 3 (nsp3) has the most variability in the proteins domains from one group to another. Nsp1, 2 and 3 are processed by one or two papain-like proteinases. It is believed that nsp2 and nsp1 protein coevolve with nsp3 and may mediate host-specific functions depending on the CoVs group. SARS-CoV-2 genome, which has a high mutation rate, the proposed nsp2 target is 100% conserved.
Because of its variation, nsp2 protein is an attractive target for further genetic studies. It is believed that nsp2 protein either has a function that is unessential for viral replication or the protein retains function in an uncleaved form.