Thymidine kinase from herpesvirus

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Thymidine kinase from herpesvirus
Structure of thymidine kinase from herpesvirus.[1]
Identifiers
SymbolHerpes_TK
PfamPF00693
InterProIPR001889
SCOP21kin / SCOPe / SUPFAM

Thymidine kinase from herpesvirus is a sub-family of thymidine kinases that catalyses the transfer of phospho group of ATP to thymidine to generate thymidine monophosphate, which serves as a substrate during viral DNA replication.[2][3]

Its presence in herpesvirus-infected cells is used to activate a range of antivirals against herpes infection, and thus specifically target the therapy towards infected cells only.

Such antivirals include:

Mutations in the gene coding thymidine kinase in herpes viruses can endow the virus with resistance to aciclovir. In these situations, alternative medications that are of use include other guanine analogues such as famciclovir, valaciclovir and penciclovir.[4][5]

Mechanism of antiviral guanosine analogue ACV and thymidine analogue N-MCT in HSV-1[6] (ACV [acyclovir] targets thymidine kinase[7][8])

References

  1. ↑ Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, et al. (August 1998). "Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands". Proteins. 32 (3): 350–361. doi:10.1002/(SICI)1097-0134(19980815)32:3<350::AID-PROT10>3.0.CO;2-8. PMID 9715911. S2CID 20167407.
  2. ↑ Vogt J, Perozzo R, Pautsch A, Prota A, Schelling P, Pilger B, et al. (December 2000). "Nucleoside binding site of herpes simplex type 1 thymidine kinase analyzed by X-ray crystallography". Proteins. 41 (4): 545–553. doi:10.1002/1097-0134(20001201)41:4<545::AID-PROT110>3.0.CO;2-8. PMID 11056041. S2CID 2829079.
  3. ↑ Brown DG, Visse R, Sandhu G, Davies A, Rizkallah PJ, Melitz C, et al. (October 1995). "Crystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir". Nature Structural Biology. 2 (10): 876–881. doi:10.1038/nsb1095-876. PMID 7552712. S2CID 3223579.
  4. ↑ Frobert E, Ooka T, Cortay JC, Lina B, Thouvenot D, Morfin F (March 2005). "Herpes simplex virus thymidine kinase mutations associated with resistance to acyclovir: a site-directed mutagenesis study". Antimicrobial Agents and Chemotherapy. 49 (3): 1055–1059. doi:10.1128/AAC.49.3.1055-1059.2005. PMC 549244. PMID 15728902.
  5. ↑ Suzuki M, Okuda T, Shiraki K (November 2006). "Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus". Antiviral Research. 72 (2): 157–161. doi:10.1016/j.antiviral.2006.05.001. PMID 16797734.
  6. ↑ Xie, Ying; Wu, Liping; Wang, Mingshu; Cheng, Anchun; Yang, Qiao; Wu, Ying; Jia, Renyong; Zhu, Dekang; Zhao, XinXin; Chen, Shun; Liu, Mafeng; Zhang, Shaqiu; Wang, Yin; Xu, Zhiwen; Chen, Zhengli; Zhu, Ling; Luo, Qihui; Liu, Yunya; Yu, Yanling; Zhang, Ling; Chen, Xiaoyue (8 May 2019). "Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets". Frontiers in Microbiology. 10: 941. doi:10.3389/fmicb.2019.00941. ISSN 1664-302X. Retrieved 19 January 2024.
  7. ↑ Rabelo, Vitor Won-Held; Romeiro, Nelilma Correia; Paixão, Izabel Christina Nunes de Palmer; Abreu, Paula Alvarez (April 2020). "Mechanism of resistance to acyclovir in thymidine kinase mutants from Herpes simplex virus type 1: a computational approach". Journal of Biomolecular Structure & Dynamics. 38 (7): 2116–2127. doi:10.1080/07391102.2019.1625443. ISSN 1538-0254.
  8. ↑ Aoki, Fred Y. (1 January 2015). "45 - Antivirals against Herpes Viruses". Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Eighth Edition). W.B. Saunders. pp. 546–562.e7. ISBN 978-1-4557-4801-3.
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