Thymidine kinase from herpesvirus

Structure of thymidine kinase from herpesvirus.[1]

Identifiers
Symbol| Herpes_TK
Pfam| PF00693
InterPro| IPR001889
SCOP2| 1kin / SCOPe / SUPFAM
| Available protein structures:

Pfam | structures / ECOD
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary
PDB| 1e2pB:56-330 1e2jB:56-330 1vtk :56-330

1of1B:56-330 1e2lA:56-330 1e2kA:56-330 1p7cA:56-330 1e2mB:56-330 1ki6A:56-330 1e2hB:56-330 3vtk :56-330 1e2nA:56-330 1e2iB:56-330 2vtk :56-330 1osnC:19-299 1p72A:32-309 1p75B:32-309 1p73D:32-309

1p6xA:32-309

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:

* Purine analogues of guanine: Aciclovir, Famciclovir, Ganciclovir, Penciclovir, Valaciclovir, Valganciclovir
* Vidarabine
* Pyrimidine analogues of uridine: Idoxuridine, Trifluridine
* Brivudine

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]

## References

[edit]

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.

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DNA virus antivirals (primarily J05, also S01AD and D06BB)

Baltimore I|

| Herpesvirus|

| DNA-synthesis
inhibitor|

| TK activated|

| Purine analogue|

* guanine (Aciclovir#/Valaciclovir
* Ganciclovir/Valganciclovir#
* Penciclovir/Famciclovir)

* adenine (Vidarabine)

|

Pyrimidine analogue|

* uridine (Idoxuridine
* Trifluridine (+tipiracil)
* Edoxudine)

* thymine
* Brivudine
* FV-100†
* Sorivudine‡

* cytosine (Cytarabine)

Not TK activated|

* Foscarnet

Other|

* Amenamevir
* Docosanol
* Letermovir
* Maribavir
* early protein (Fomivirsen‡)
* Tromantadine

HPV/MC|

* Imiquimod/Resiquimod
* Podophyllotoxin

Vaccinia|

* assembly: Rifampicin

Poxviridae|

* Methisazone
* Tecovirimat

Hepatitis B (VII)|

* Nucleoside analogues/NARTIs: Entecavir#
* Lamivudine
* Lobucavir†
* Telbivudine
* Clevudine

* Nucleotide analogues/NtRTIs: Adefovir
* Tenofovir disoproxil
* Tenofovir alafenamide

Multiple/general|

| Nucleic acid inhibitors|

* Cidofovir
* Brincidofovir

|

Interferon|

* Interferon alfa 2b
* Peginterferon alfa-2a

Multiple/unknown|

* Filociclovir†
* Ribavirin#/Taribavirin†
* Moroxydine

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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