NSP13

General information on NSP13

Nonstructural protein 13 (nsp13) is a superfamily 1 helicase that has been found in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is the coronavirus strain that causes 2019 Novel Coronavirus disease (COVID-19). Broadly speaking, coronavirus (CoVs) are large single-stranded positive-sense RNA viruses with 5′-cap and 3′-poly-A tail. SARS-CoV-2 genome consists of several open reading frames (ORFs). The first ORF (ORF 1a/b) encoded 16 non-structural proteins. These proteins are essential for CoV replication.
Helicases are defined as motor proteins that unwind a double-stranded (ds) nucleic acid into two single-stranded (ss) nucleic acids using energy derived from NTP hydrolysis during translocation along a single strand for nucleic acid replication, recombination, and DNA repair. As a helicase, nsp13 is able to unwind both dsRNA and dsDNA with a 5′-ss tail along the polarity of 5′ to 3’. It’s also capable of hydrolysing all deoxyribonucleotide and ribonucleotide triphosphates. The COVID-19 virus unwind the RNA duplex and the host DNA with a 5′ single-stranded tail in a 5′ to 3′ direction. Np13 is also able to unwind DNA duplex by cooperative translocation. Nsp13 has different characteristics whether it’s unwinding RNA duplex or DNA one. The protein has better processivity on DNA duplex compared to that on duplex RNA. Nsp13 becomes less efficient in unwinding duplex RNA as 5′-ss tail length increases. However, higher nsp13 concentration lead to higher amount of unwound duplex DNA and decreased unwound duplex RNA. Increased nsp13 concentration also results in an accumulation of duplex RNA/nsP13 complex. Increased quantities of ATP are required for RNA unwinding. Higher levels of ATP increase nsp13 has affinity for duplex RNA as a substrate.
Because of the importance of this helicase in viral replication and proliferation, nsp13 is considered as a potential target for antiviral treatment. It is believed that inhibiting this target can impair viral metabolism without affecting normal cells.