nsp13

Nsp13 of SARS coronavirus is a helicase capable of unwinding both RNA and DNA duplexes in a 5'-to-3' direction with remarkable processivity. It possesses deoxynucleoside triphosphatase (dNTPase) activity against all standard nucleotides and deoxynucleotides, and also RNA 5'-triphosphatase activity which may be involved in the formation of the 5' cap structure of the viral mRNAs. The two hydrolase activities likely have a common active site. Since NTPase/helicase proteins are considered essential for viral viability, they are potential drug targets. Promising inhibitors are in trials for herpes simplex virus and hepatitis C viral infections. Several SARS-CoV helicase inhibitors – bananin derivatives – have been identified in a recent study. While a theoretical molecular model for nsp13 has been proposed, the structure of this protein (or its different domains) is yet to be determined. Further, the role of the metal-binding cysteine-rich N-terminal domain in helicase activity also remains unclear.

Ivanov KA, Thiel V, Dobbe JC, van der Meer Y, Snijder EJ, Ziebuhr J. Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J Virol. 2004 Jun;78(11):5619-32.

Tanner JA, Watt RM, Chai YB, Lu LY, Lin MC, Peiris JS, Poon LL, Kung HF, Huang JD. The severe acute respiratory syndrome (SARS) coronavirus NTPase/helicase belongs to a distinct class of 5' to 3' viral helicases. J Biol Chem. 2003 Oct 10;278(41):39578-82. Epub 2003 Aug 13.

Frick DN, Lam AM.    Understanding helicases as a means of virus control. Curr Pharm Des. 2006;12(11):1315-38.

Bernini A, Spiga O, Venditti V, Prischi F, Bracci L, Huang J, Tanner JA, Niccolai N. Tertiary structure prediction of SARS coronavirus helicase. Biochem Biophys Res Commun. 2006 May 19;343(4):1101-4. Epub 2006 Mar 23.

Kesel AJ. Synthesis of novel test compounds for antiviral chemotherapy of severe acute respiratory syndrome (SARS). Curr Med Chem. 2005;12(18):2095-162.

Kao RY, Tsui WH, Lee TS, Tanner JA, Watt RM, Huang JD, Hu L, Chen G, Chen Z, Zhang L, He T, Chan KH, Tse H, To AP, Ng LW, Wong BC, Tsoi HW, Yang D, Ho DD, Yuen KY. Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics. Chem Biol. 2004;11(9):1293-9.

Sawicki, S. G., Sawicki, D. L., Siddell, S. G. (2007). A Contemporary View of Coronavirus Transcription. J. Virol. 81: 20-29