Nonstructural protein 13 – helicase

The nonstructural protein 13 (nsp13) is involved in a number of functions, such as NTPase, dNTPase, RTpase, RNA helicase, and DNA helicase activity. A single mutation in SARS-CoV-1 nsp13 stalk domain, resulted in a dramatic decrease in viral infectivity in vitro. The essential nature of nsp13 in the viral replication cycle, and its multifunctional nature has made it an attractive target for vaccine research. SARS-CoV-2 nsp13 is fully conserved relative to SARS-CoV-1.

Narrative

The nonstructural protein 13 (nsp13), encoded from ORF1ab as part of the pp1ab polyprotein, is involved in a number of functions, such as NTPase, dNTPase, RTpase, RNA helicase, and DNA helicase activity (Ivanov and Ziebuhr 2004). It also interacts with nsp12, which is thought to enhance its helicase activity (Ivanov and Ziebuhr 2004; Adedeji et al. 2012).

Structural analysis and comparison with SARS-CoV-1 nsp13 – The helicase nsp13 contains 5 domains, an N-terminal zinc-binding domain, stalk domain, RecA-like domain 1A, 1B, and RecA-like domain 2A, all together consisting of 603 residues. It forms a triangular structure with the 2A and 1A as the base (Jia et al. 2019).

The zinc-binding domain consists of conserved cysteine residues, which have shown to be essential for the various enzymatic activities of nsp13 (Seybert et al. 2005) The stalk domain links the zinc-binding domain to the rest of the helicase, where the stalk domain has been argued to serve as an essential signal transduction mechanism (Jia et al. 2019) A single mutation in the stalk domain of SARS-CoV-1 nsp13, Arg¹³²Pro, resulted in a dramatic decrease in viral infectivity in vitro (S. Fang et al. 2007) The essential nature of nsp13 in the viral replication cycle, and its multifunctional nature has made it an attractive target for vaccine research (Z. Wang et al. 2011, Briguglio et al. 2011; Adedeji et al. 2014) SARS-CoV-2 nsp13 is fully conserved relative to SARS-CoV-1.