Thymidine Kinase From Herpesvirus
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Thymidine Kinase From Herpesvirus
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. 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 analogue Pyrimidine analogues are antimetabolites which mimic the structure of metabolic pyrimidines. Examples * Nucleobase analogues **Fluorouracil (5FU), which inhibits thymidylate synthase **Floxuridine (FUDR) ** 6-azauracil (6-AU) *Nucleoside analogue ...s of uridine: Idoxuridine, Trifluridine * Brivudine Mutations in the gene coding thymidine kinase in herpes viruses can endow the virus with resistan ...
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Herpesvirus
''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπειν'' ( 'to creep'), referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established ''Herpesvirus'' as a genus with 23 viruses among four groups. As of 2020, 115 species are recognized, all but one of which are in one of the three subfamilies. Herpesviruses can cause both latent and lytic infections. Nine herpesvirus types are known to primarily infect humans, at least five of which – herpes simplex viruses 1 and 2 (HSV-1 and HSV-2, also known as HHV-1 and HHV-2; both of which can cause orolabial herpes and genital herpes), varicella zoster virus (or HHV-3; the cause o ...
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Valaciclovir
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. Common side effects include headache and vomiting. Severe side effects may include kidney problems. Use in pregnancy appears to be safe. It is a prodrug, which works after being converted to aciclovir in a person's body. Valaciclovir was patented in 1987 and came into medical use in 1995. It is on the WHO Model List of Essential Medicines, World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2020, it was the 119th most commonly prescribed medication in the United States, with more than 5million prescriptions. Medical uses Valaciclovir is used for the treatment of HSV and VZV infections, including:Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicin ...
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Brivudine
Brivudine (trade names Zostex, Mevir, Brivir, among others) is an antiviral drug used in the treatment of herpes zoster ("shingles"). Like other antivirals, it acts by inhibiting replication of the target virus. Medical uses Brivudine is used for the treatment of herpes zoster in adult patients. It is taken orally once daily, in contrast to aciclovir, valaciclovir and other antivirals. A study has found that it is more effective than aciclovir, but this has been disputed because of a possible conflict of interest on part of the study authors. Contraindications The drug is contraindicated in patients undergoing immunosuppression (for example because of an organ transplant) or cancer therapy, especially with fluorouracil (5-FU) and chemically related (pro)drugs such as capecitabine and tegafur, as well as the antimycotic drug flucytosine, which is also related to 5-FU. It has not been proven to be safe in children and pregnant or breastfeeding women. Adverse effects The drug is g ...
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Trifluridine
Trifluridine (also called trifluorothymidine; abbreviation TFT or FTD) 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. Trifluridine was approved for medical use in 1980. It is also a component of the anti-cancer drug trifluridine/tipiracil, which is taken by mouth. Medical uses Trifluridine eye drops are used for the treatment of keratitis and keratoconjunctivitis caused by the herpes simplex virus types 1 and 2, as well as for prevention and treatment of vaccinia virus infections of the eye. A Cochrane Systematic Review showed that trifluridine and aciclovir were a more effective treatment than idoxuridine or vidarabine, significantly increasing the relative number of successfully healed eyes in one to two weeks. For cancer treatment, the combination trifluridine/ti ...
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Idoxuridine
Idoxuridine is an anti-herpesvirus antiviral drug. It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the iodine atom added to the uracil component blocks base pairing. It is used only topically due to cardiotoxicity. It was synthesized by William Prusoff in the late 1950s. Initially developed as an anticancer drug, idoxuridine became the first antiviral agent in 1962. Clinical use Idoxuridine is mainly used topically to treat herpes simplex keratitis.Goodman and Gilman's The Pharmacological Basis of Therapeutics. Edited by Gilman AG, Rall TW, Nies AS, Taylor P. McGraw-Hill. 8th ed. 1990. Epithelial lesions, especially initial attacks presenting with a dendritic ulcer, are most responsive to therapy, while infection with stromal involvement are less responsive. Idoxuridine is ineffective against herpes simplex virus type 2 and varicella-zoster. Side effects Common side effects of the eye drops include irr ...
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Uridine
Uridine (symbol U or Urd) is a glycosylated pyrimidine analog containing uracil attached to a ribose ring (or more specifically, a ribofuranose) via a β-N1-glycosidic bond. The analog is one of the five standard nucleosides which make up nucleic acids, the others being adenosine, thymidine, cytidine and guanosine. The five nucleosides are commonly abbreviated to their symbols, U, A, dT, C, and G, respectively. However, thymidine is more commonly written as 'dT' ('d' represents 'deoxy') as it contains a 2'-deoxyribofuranose moiety rather than the ribofuranose ring found in uridine. This is because thymidine is found in deoxyribonucleic acid (DNA) and usually not in ribonucleic acid (RNA). Conversely, uridine is found in RNA and not DNA. The remaining three nucleosides may be found in both RNA and DNA. In RNA, they would be represented as A, C and G whereas in DNA they would be represented as dA, dC and dG. Biosynthesis Uridine is widely produced in nature as uridine monophosp ...
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Pyrimidine Analogue
Pyrimidine analogues are antimetabolites which mimic the structure of metabolic pyrimidines. Examples * Nucleobase analogues **Fluorouracil (5FU), which inhibits thymidylate synthase **Floxuridine (FUDR) ** 6-azauracil (6-AU) *Nucleoside analogues **Cytarabine (Cytosine arabinoside) **Gemcitabine *Nucleotide analogues File:Pyrimidin.svg, Pyrimidine File:Fluorouracil.svg, Fluorouracil File:Floxuridine.png, Floxuridine File:Gemcitabine.svg, Gemcitabine Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by ... Medical uses Pyrimidine antimetabolites are commonly used to treat cancer by interfering with DNA replication. References Antimetabolites Metabolism Pyrimidines {{biochem-stub ...
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Vidarabine
Vidarabine or 9-β-D-arabinofuranosyladenine (ara-A) is an antiviral drug which is active against herpes simplex and varicella zoster viruses. Discovery In the 1950s two nucleosides were isolated from the Caribbean sea sponge, sponge ''Tethya crypta'': spongothymidine and spongouridine; which contained D-arabinose rather than D-ribose. These compounds led to the synthesis of a new generation, sugar modified nucleoside analog vidarabine, and the related compound cytarabine. In 2004 these were the only marine related compounds in clinical use. The drug was first synthesized in 1960 in the Bernard Randall Baker lab at the SRI International, Stanford Research Institute (now SRI International). The drug was originally intended as an anti-cancer drug. The anti-viral activity of vidarabine was first described by M. Privat de Garilhe and J. De Rudder in 1964. It was the first nucleoside analog antiviral drug, antiviral to be given systemically and was the first agent to be licensed f ...
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Valganciclovir
Valganciclovir, sold under the brand name Valcyte among others, is an antiviral medication used to treat cytomegalovirus (CMV) infection in those with HIV/AIDS or following organ transplant. It is often used long term as it only suppresses rather than cures the infection. Valganciclovir is taken by mouth. Common side effects include abdominal pain, headaches, trouble sleeping, nausea, fever, and low blood cell counts. Other side effects may include infertility and kidney problems. When used during pregnancy, it causes birth defects in some animals. Valganciclovir is the L- valyl ester of ganciclovir and works when broken down into ganciclovir by the intestine and liver. Valganciclovir was approved for medical use in 2001. It is on the World Health Organization's List of Essential Medicines. In 2017, a generic version was approved. Medical uses Adults Valganciclovir is commonly used for treatment of cytomegalovirus (CMV) retinitis (eye infection may cause blindness) ...
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Penciclovir
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 (by mouth) it is more often used as a topical treatment. It is the active ingredient in the cold sore medications Denavir ( NDC 0135-0315-52), Vectavir and Fenivir. Famciclovir is a prodrug of penciclovir with improved oral bioavailability. Penciclovir was approved for medical use in 1996. Medical use In herpes labialis, the duration of healing, pain and detectable virus is reduced by up to one day,Fass.se">Farmaceutiska Specialiteter i Sverige - the Swedish official drug catalog Vectavir. Retrieved on August 12, 2009. Translated from "Tiden för läkning, smärta och påvisbart virus förkortas med upp till ett dygn." compared with the total duration of 2–3 weeks of disease presentation. Mechanism of action Penciclovir is inactive in i ...
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Protein Family
A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be confused with Family (biology), family as it is used in taxonomy. Proteins in a family descend from a common ancestor and typically have similar protein structure, three-dimensional structures, functions, and significant Sequence homology, sequence similarity. The most important of these is sequence similarity (usually amino-acid sequence), since it is the strictest indicator of homology and therefore the clearest indicator of common ancestry. A fairly well developed framework exists for evaluating the significance of similarity between a group of sequences using sequence alignment methods. Proteins that do not share a common ancestor are very unlikely to show statistically significant sequence similarity, making sequence alignment a powerf ...
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Ganciclovir
Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections. Ganciclovir was patented in 1980 and approved for medical use in 1988. Medical use Ganciclovir is indicated for:Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. * Sight-threatening CMV retinitis in severely immunocompromised people * CMV pneumonitis in bone marrow transplant recipients * Prevention of CMV disease in bone marrow and solid organ transplant recipients * Confirmed CMV retinitis in people with AIDS (intravitreal implant) It is also used for acute CMV colitis in HIV/AIDS and CMV pneumonitis in immunosuppressed patients. Ganciclovir has also been used with some success in treating ''Human herpesvirus 6'' infections. Ganciclovir has also been found to be an effective treatment for herpes simplex virus epithelial keratitis. Adverse effects Ganciclovir is commonly associated with a r ...
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