Thymidine kinase from herpesvirus

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Thymidine kinase from herpesvirus
PDB 1kim EBI.jpg
Structure of thymidine kinase from herpesvirus. [1]
Identifiers
SymbolHerpes_TK
Pfam PF00693
InterPro IPR001889
SCOP2 1kin / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1e2p B:56-330 1e2j B:56-330 1vtk :56-330

1of1 B:56-330 1e2l A:56-330 1e2k A:56-330 1p7c A:56-330 1e2m B:56-330 1ki6 A:56-330 1e2h B:56-330 3vtk :56-330 1e2n A:56-330 1e2i B:56-330 2vtk :56-330 1osn C:19-299 1p72 A:32-309 1p75 B:32-309 1p73 D:32-309

1p6x A: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:

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]

Related Research Articles

<span class="mw-page-title-main">Aciclovir</span> Antiviral medication used against herpes, chickenpox and shingles

Aciclovir (ACV), also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following transplant and severe complications of Epstein–Barr virus infection. It can be taken by mouth, applied as a cream, or injected.

<span class="mw-page-title-main">Valaciclovir</span> Anti-herpes virus drug

Valaciclovir, also spelled valacyclovir, is an antiviral medication used to treat outbreaks of herpes simplex or herpes zoster (shingles). It is also used to prevent cytomegalovirus following a kidney transplant in high risk cases. It is taken by mouth.

<span class="mw-page-title-main">Thymidine kinase</span> Enzyme found in most living cells

Thymidine kinase is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.21. It can be found in most living cells. It is present in two forms in mammalian cells, TK1 and TK2. Certain viruses also have genetic information for expression of viral thymidine kinases. Thymidine kinase catalyzes the reaction:

<span class="mw-page-title-main">Vidarabine</span> Chemical compound

Vidarabine or 9-β-D-arabinofuranosyladenine (ara-A) is an antiviral drug which is active against herpes simplex and varicella zoster viruses.

<span class="mw-page-title-main">Ganciclovir</span> Chemical compound

Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections.

<span class="mw-page-title-main">Nucleoside analogue</span> Biochemical compound

Nucleoside analogues are nucleosides which contain a nucleic acid analogue and a sugar. Nucleotide analogs are nucleotides which contain a nucleic acid analogue, a sugar, and a phosphate group with one to three phosphates.

<span class="mw-page-title-main">Brivudine</span> Chemical compound

Brivudine is an antiviral drug used in the treatment of herpes zoster ("shingles"). Like other antivirals, it acts by inhibiting replication of the target virus.

<span class="mw-page-title-main">Famciclovir</span> Chemical compound

Famciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster (shingles). It is a prodrug form of penciclovir with improved oral bioavailability. Famciclovir is marketed under the trade name Famvir (Novartis).

<span class="mw-page-title-main">Herpes simplex virus</span> Species of virus

Herpes simplex virus1 and 2, also known by their taxonomic names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are very common and contagious. They can be spread when an infected person begins shedding the virus.

<span class="mw-page-title-main">Genital herpes</span> Infection by herpes simplex viruses of the genitals

Genital herpes is an infection by the herpes simplex virus (HSV) of the genitals. Most people either have no or mild symptoms and thus do not know they are infected. When symptoms do occur, they typically include small blisters that break open to form painful ulcers. Flu-like symptoms, such as fever, aching, or swollen lymph nodes, may also occur. Onset is typically around 4 days after exposure with symptoms lasting up to 4 weeks. Once infected further outbreaks may occur but are generally milder.

<span class="mw-page-title-main">Foscarnet</span> Chemical compound

Foscarnet (phosphonomethanoic acid), known by its brand name Foscavir, is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate analog DNA polymerase inhibitor. Foscarnet is the conjugate base of a chemical compound with the formula HO2CPO3H2 (Trisodium phosphonoformate).

<span class="mw-page-title-main">Penciclovir</span> Chemical compound

Penciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections. It is a nucleoside analogue which exhibits low toxicity and good selectivity. Because penciclovir is absorbed poorly when given orally it is more often used as a topical treatment. It is the active ingredient in the cold sore medications Denavir, Vectavir and Fenivir. Famciclovir is a prodrug of penciclovir with improved oral bioavailability.

<span class="mw-page-title-main">Idoxuridine</span> Chemical compound

Idoxuridine is an anti-herpesvirus antiviral drug.

<span class="mw-page-title-main">Trifluridine</span> Chemical compound

Trifluridine is an anti-herpesvirus antiviral drug, used primarily on the eye. It was sold under the trade name Viroptic by Glaxo Wellcome, now merged into GlaxoSmithKline. The brand is now owned by Monarch Pharmaceuticals, which is wholly owned by King Pharmaceuticals.

<span class="mw-page-title-main">Sorivudine</span> Chemical compound

Sorivudine (INN), is a nucleoside analogue antiviral drug, marketed under trade names such as Usevir and Brovavir (BMS). It is used for the treatment of varicella zoster virus infections.

<span class="mw-page-title-main">Herpes simplex</span> Viral disease caused by herpes simplex viruses

Herpes simplex is a viral infection caused by the herpes simplex virus. Infections are categorized based on the part of the body infected.

<span class="mw-page-title-main">Cold sore</span> Herpes simplex virus infection of the lip

A cold sore, also known as a fever blister and herpes labialis, is a type of infection by the herpes simplex virus that affects primarily the lip. Symptoms typically include a burning pain followed by small blisters or sores. The first attack may also be accompanied by fever, sore throat, and enlarged lymph nodes. The rash usually heals within ten days, but the virus remains dormant in the trigeminal ganglion. The virus may periodically reactivate to create another outbreak of sores in the mouth or lip.

<span class="mw-page-title-main">Herpes simplex keratitis</span> Medical condition

Herpetic simplex keratitis is a form of keratitis caused by recurrent herpes simplex virus (HSV) infection in the cornea.

<span class="mw-page-title-main">Pritelivir</span> Chemical compound

Pritelivir is a direct-acting antiviral drug in development for the treatment of herpes simplex virus infections (HSV). This is particularly important in immune compromised patients. Pritelivir is currently in Phase III clinical development by the German biopharmaceutical company AiCuris Anti-infective Cures AG.

HSV epigenetics is the epigenetic modification of herpes simplex virus (HSV) genetic code.

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.