Nucleoside analogues
Encyclopedia
Nucleoside analogues are a range of antiviral products used to prevent viral
replication in infected cells. The most commonly used is Acyclovir, although its inclusion in this category is uncertain, as it contains only a partial nucleoside
structure, as the sugar ring
is replaced by an open-chain structure.
, hepatitis C virus
, herpes simplex
, and HIV
. Once they are phosphorylated
, they work as antimetabolite
s by being similar enough to nucleotide
s to be incorporated into growing DNA
strands; but they act as chain terminators and stop viral DNA Polymerase. They are not specific to viral DNA and also affect mitochondrial DNA. Because of this they have side effects such as bone marrow suppression.
There is a large family of nucleoside analogue reverse transcriptase inhibitors, because DNA production by reverse transcriptase
is very different from normal human DNA replication
, so it is possible to design nucleoside analogues that are preferentially incorporated by the former. Some nucleoside analogues, however, can function both as NRTIs and polymerase inhibitors for other viruses (e.g., hepatitis B). Less selective nucleoside analogues are used as chemotherapy
agents to treat cancer
.
Related drugs are nucleobase
analogues such as Aciclovir
and nucleotide analogues.
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
replication in infected cells. The most commonly used is Acyclovir, although its inclusion in this category is uncertain, as it contains only a partial nucleoside
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...
structure, as the sugar ring
Pentose
A pentose is a monosaccharide with five carbon atoms. Pentoses are organized into two groups. Aldopentoses have an aldehyde functional group at position 1...
is replaced by an open-chain structure.
Function
These agents can be used against hepatitis B virusHepatitis B virus
Hepatitis B is an infectious illness caused by hepatitis B virus which infects the liver of hominoidea, including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis", the disease has caused epidemics in parts of Asia and Africa, and it is endemic in China...
, hepatitis C virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
, herpes simplex
Herpes simplex
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...
, and HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. Once they are phosphorylated
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
, they work as antimetabolite
Antimetabolite
An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid...
s by being similar enough to nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s to be incorporated into growing DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
strands; but they act as chain terminators and stop viral DNA Polymerase. They are not specific to viral DNA and also affect mitochondrial DNA. Because of this they have side effects such as bone marrow suppression.
There is a large family of nucleoside analogue reverse transcriptase inhibitors, because DNA production by reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
is very different from normal human DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
, so it is possible to design nucleoside analogues that are preferentially incorporated by the former. Some nucleoside analogues, however, can function both as NRTIs and polymerase inhibitors for other viruses (e.g., hepatitis B). Less selective nucleoside analogues are used as chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
agents to treat cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
.
Resistance
Resistance can develop quickly with as little as one mutation. Mutations occur in the enzymes that phosphorylate the drug to activate it.Examples
Nucleoside analogue drugs include:- deoxyadenosineDeoxyadenosineDeoxyadenosine is a deoxyribonucleoside. It is a derivative of the nucleoside adenosine, differing from the latter by the replacement of a hydroxyl group by hydrogen at the 2' position of its ribose sugar moiety. Deoxyadenosine is the DNA nucleoside A, which pairs with deoxythymidine in...
analogues- DidanosineDidanosineDidanosine is sold under the trade names Videx and Videx EC. It is a reverse transcriptase inhibitor, effective against HIV and used in combination with other antiretroviral drug therapy as part of highly active antiretroviral therapy .-History:The related pro-drug of didanosine,...
(ddI)(HIV) - VidarabineVidarabineVidarabine or adenine arabinoside is an antiviral drug which is active against herpes simplex and varicella zoster viruses.- How the drug was discovered :...
(chemotherapy)
- Didanosine
- deoxycytidineDeoxycytidineDeoxycytidine is a deoxyribonucleoside. It is like cytidine, but with one oxygen atom removed....
analogues- CytarabineCytarabineCytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia and non-Hodgkin lymphoma. It is also known as Ara-C...
(chemotherapy) - EmtricitabineEmtricitabineEmtricitabine , with trade name Emtriva , is a nucleoside reverse transcriptase inhibitor for the treatment of HIV infection in adults and children....
(FTC)(HIV) - LamivudineLamivudineLamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
(3TC)(HIV, hepatitis B) - Zalcitabine (ddC)(HIV)
- Cytarabine
- deoxyguanosineDeoxyguanosineDeoxyguanosine is composed of the purine nucleoside guanine linked by its N9 nitrogen to the C1 carbon of deoxyribose. It is similar to guanosine, but with one hydroxyl group removed from the 2' position of the ribose sugar . If a phosphate group is attached at the 5' position, it becomes...
analogues- AbacavirAbacavirAbacavir is a nucleoside analog reverse transcriptase inhibitor used to treat HIV and AIDS. It is available under the trade name Ziagen and in the combination formulations Trizivir and Kivexa/Epzicom...
(HIV) - EntecavirEntecavirEntecavir INN , abbreviated ETV, is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade name Baraclude ....
(hepatitis B)
- Abacavir
- (deoxy-)thymidineThymidineThymidine is a chemical compound, more precisely a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine in double-stranded DNA...
analogues- StavudineStavudineStavudine is a nucleoside analog reverse transcriptase inhibitor active against HIV.-History:...
(d4T) - TelbivudineTelbivudineTelbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo and Tyzeka...
(hepatitis B) - ZidovudineZidovudineZidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
(azidothymidine, or AZT)(HIV)
- Stavudine
- deoxyuridineDeoxyuridineDeoxyuridine is a compound and a nucleoside. It is similar in chemical structure to uridine, but without the 2'-hydroxyl group.Idoxuridine and Trifluridine are variants of deoxyuridine used as antiviral drugs...
analogues- IdoxuridineIdoxuridineIdoxuridine 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...
- TrifluridineTrifluridineTrifluridine 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...
- Idoxuridine
Related drugs are nucleobase
Nucleobase
Nucleobases are a group of nitrogen-based molecules that are required to form nucleotides, the basic building blocks of DNA and RNA. Nucleobases provide the molecular structure necessary for the hydrogen bonding of complementary DNA and RNA strands, and are key components in the formation of stable...
analogues such as Aciclovir
Aciclovir
Aciclovir or acyclovir , chemical name acycloguanosine, abbreviated as ACV,is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax, Zovirax, and Zovir...
and nucleotide analogues.
See also
- For nucleoside analogues in biology, see Nucleic acid analoguesNucleic acid analoguesNucleic acid analogues are compounds structurally similar to naturally occurring RNA and DNA, used in medicine and in molecular biology research....