The Holý Trinity: the acyclic nucleoside phosphonates. 2013

Erik De Clercq
Rega Institute for Medical Research, KU Leuven, Leuven, Belgium. erik.declercq@rega.kuleuven.be

The Holý Trinity was named after Dr Antonín Holý (the Holý Trinity being an Unesco recognized monument in Olomouc, Czech Republic), who together with Dr John C. Martin (Gilead Sciences) and myself pioneered a new class of antiviral agents, the acyclic nucleoside phosphonates. These compounds have revolutionized the antiviral drug field with several drugs that have been approved for the treatment of various DNA virus infections (cidofovir), hepatitis B (adefovir), and AIDS (HIV infection; tenofovir). The latter is also available as its oral prodrug, tenofovir disoproxil fumarate, for the treatment of hepatitis B and in combination with emtricitabine ((-)FTC) for the treatment and prophylaxis of HIV infections and in combination with (-)FTC and other HIV inhibitors, that is, efavirenz, rilpivirine, or elvitegravir (and a pharmacoenhancer thereof, cobicistat), for the treatment of AIDS.

UI MeSH Term Description Entries
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D003596 Cytosine A pyrimidine base that is a fundamental unit of nucleic acids.
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068698 Tenofovir An adenine analog REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B. It is used to treat HIV INFECTIONS and CHRONIC HEPATITIS B, in combination with other ANTIVIRAL AGENTS, due to the emergence of ANTIVIRAL DRUG RESISTANCE when it is used alone. (R)-9-(2-phosphonylmethoxypropyl)adenine,9-(2-Phosphonomethoxypropyl)adenine,9-(2-Phosphonylmethoxypropyl)adenine,9-(2-Phosphonylmethoxypropyl)adenine, (+-)-isomer,9-(2-Phosphonylmethoxypropyl)adenine, (R)-isomer - T357098,9-(2-Phosphonylmethoxypropyl)adenine, (S)-isomer,9-PMPA (tenofovir),Tenofovir Disoproxil,Tenofovir Disoproxil Fumarate,Viread,Disoproxil Fumarate, Tenofovir,Disoproxil, Tenofovir,Fumarate, Tenofovir Disoproxil
D000077404 Cidofovir An acyclic nucleoside phosphonate that acts as a competitive inhibitor of viral DNA polymerases. It is used in the treatment of RETINITIS caused by CYTOMEGALOVIRUS INFECTIONS and may also be useful for treating HERPESVIRUS INFECTIONS. 1-((3-Hydroxy-2-phosphonylmethoxy)propyl)cytosine,1-(3-Hydroxy-2-phosphonylmethoxypropyl)cytosine,Cidofovir Anhydrous,Cidofovir Sodium,Cidofovir, (+-)-isomer,Cidofovir, (R)-isomer,Cidofovir, Sodium Salt,GS 504,GS-504,HPMPC,Vistide,GS504
D000225 Adenine A purine base and a fundamental unit of ADENINE NUCLEOTIDES. Vitamin B 4,4, Vitamin B,B 4, Vitamin
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D014777 Virus Diseases A general term for diseases caused by viruses. Viral Diseases,Viral Infections,Virus Infections,Disease, Viral,Disease, Virus,Diseases, Viral,Diseases, Virus,Infection, Viral,Infection, Virus,Infections, Viral,Infections, Virus,Viral Disease,Viral Infection,Virus Disease,Virus Infection

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