nsp13

nsp13 is a viral non-structural protein encoded by the coronavirus genome. It is produced from the ORF1a/1b polyproteins and becomes part of the replication-transcription complex (RTC) after proteolytic processing by viral proteases.

Structure: It contains an N-terminal zinc-binding domain (ZBD) with bound zinc coordinated by cysteine and histidine residues, followed by a stalk region and two RecA-like helicase domains (1A and 2A) that form the active core. The protein belongs to the SF1 helicases and functions as a 5' to 3' RNA helicase with ATPase activity.

Function: nsp13 unwinds double-stranded RNA ahead of the replication/transcription machinery, using energy from ATP hydrolysis. It translocates along RNA in the 5' to 3' direction and is thought to coordinate with the RNA-dependent RNA polymerase nsp12 and its cofactors nsp7 and nsp8, facilitating efficient synthesis of viral RNA. The helicase activity is highly conserved and essential for replication.

Clinical relevance and research: Because of its essential role and conserved nature, nsp13 is investigated as a potential antiviral target. Structural studies by X-ray crystallography and cryo-EM have revealed the arrangement of its domains and the ATPase/helicase mechanism. Several inhibitors have been studied in vitro, but no approved nsp13-targeted antiviral exists.

Genomic context and evolution: In SARS-CoV-2, nsp13 is encoded within ORF1ab and produced after proteolytic processing of the polyprotein; its sequence is conserved across the betacoronavirus lineage.