Nucleoside analogue

Short description: Biochemical compound

You can help expand this article with text translated from the corresponding article in Deutsch.  (December 2020) Click [show] for important translation instructions.

* View a machine-translated version of the Deutsch article.
* Machine translation, like DeepL or Google Translate, is a useful starting point for translations, but translators must revise errors as necessary and confirm that the translation is accurate, rather than simply copy-pasting machine-translated text into the English Wikipedia.
* Do not translate text that appears unreliable or low-quality. If possible, verify the text with references provided in the foreign-language article.
* You must provide copyright attribution in the edit summary accompanying your translation by providing an interlanguage link to the source of your translation. A model attribution edit summary is `Content in this edit is translated from the existing Deutsch Wikipedia article at [[:de:Nukleosid-Analogon]]; see its history for attribution.`
* You may also add the template `{{Translated|de|Nukleosid-Analogon}}` to the talk page.
* For more guidance, see Wikipedia:Translation.

|

The antiviral drug aciclovir (bottom), a nucleoside analogue that functions by mimicking guanosine (top)

Nucleoside analogues are structural analogues of a nucleoside, which normally contain a nucleobase and a sugar. Nucleotide analogues are analogues of a nucleotide, which normally has one to three phosphates linked to a nucleoside. Both types of compounds can deviate from what they mimick in a number of ways, as changes can be made to any of the constituent parts (nucleobase, sugar, phosphate).[1] They are related to nucleic acid analogues.

Nucleoside and nucleotide analogues can be used in therapeutic drugs, including a range of antiviral products used to prevent viral replication in infected cells. The most commonly used is acyclovir.

Nucleotide and nucleoside analogues can also be found naturally. Examples include ddhCTP (3ʹ-deoxy-3′,4ʹdidehydro-CTP) produced by the human antiviral protein viperin[2] and sinefungin (a S-Adenosyl methionine analogue) produced by some Streptomyces.[3]

## Contents

* 1 Function
* 2 Resistance
* 3 Examples
* 4 See also
* 5 References
* 6 Further reading

## Function

These agents can be used against hepatitis B virus, hepatitis C virus, herpes simplex, and HIV. Once they are phosphorylated, they work as antimetabolites by being similar enough to nucleotides 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, e.g. gemcitabine. They are also used as antiplatelet drugs to prevent the formation of blood clots, ticagrelor and cangrelor.

## Resistance

Resistance can develop quickly with as little as one mutation.[4] Mutations occur in the enzymes that phosphorylate the drug and activate it: in the case of herpes simplex, resistance to acyclovir[5] arises due to a mutation affecting the viral enzyme thymidine kinase.[6] Since nucleoside analogues require two phosphorylations to be activated, one carried out by a viral enzyme and the other by enzymes in the host cell, mutations in viral thymidine kinase interfere with the first of these phosphorylations; in such cases the drug remains ineffective. There are, however, several different nucleoside analogue drugs and resistance to one of them is usually overcome by switching to another drug of the same kind (e.g. famciclovir, penciclovir, valaciclovir).

## Examples

Nucleoside analogue drugs include:

* adenosine and deoxyadenosine analogues:
* didanosine (ddI) — HIV
* islatravir (ISL) — HIV
* vidarabine — antiviral
* adenosine analogues:
* galidesivir — Ebolavirus,
* remdesivir — Ebolavirus, Marburg virus, Coronavirus
* deoxycytidine analogues:
* cytarabine — chemotherapy
* gemcitabine — chemotherapy
* emtricitabine (FTC) — HIV, hepatitis B virus
* lamivudine (3TC) — HIV, hepatitis B virus
* zalcitabine (ddC) — HIV
* guanosine and deoxyguanosine analogues:
* abacavir (ABC) — HIV
* aciclovir — antiviral
* entecavir (ETV) — hepatitis B virus
* ganciclovir — Cytomegalovirus
* lobucavir — antiviral
* penciclovir — Herpesvirus
* ribavirin — antiviral
* thymidine and deoxythymidine analogues:
* brivudine — Herpesvirus
* clevudine — hepatitis B virus
* sorivudine — Herpesvirus
* stavudine (d4T) — HIV
* telbivudine (LdT) — hepatitis B virus
* zidovudine (azidothymidine, AZT) — HIV
* deoxyuridine analogues:
* idoxuridine — Herpesvirus
* trifluridine — Herpesvirus

Related drugs are nucleobase analogs, which don't include a sugar or sugar analog, and nucleotide analogues, which also include phosphate groups.

## See also

* For nucleoside analogues in biology, see nucleic acid analogues

## References

1. ↑ Seley-Radtke, KL; Yates, MK (June 2018). "The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold.". Antiviral Research 154: 66–86. doi:10.1016/j.antiviral.2018.04.004. PMID 29649496.
2. ↑ "A naturally occurring antiviral ribonucleotide encoded by the human genome". Nature (Springer Science and Business Media LLC) 558 (7711): 610–614. June 2018. doi:10.1038/s41586-018-0238-4. PMID 29925952. Bibcode: 2018Natur.558..610G.
3. ↑ Vedel, M; Lawrence, F; Robert-Gero, M; Lederer, E (14 November 1978). "The antifungal antibiotic sinefungin as a very active inhibitor of methyltransferases and of the transformation of chick embryo fibroblasts by Rous sarcoma virus.". Biochemical and Biophysical Research Communications 85 (1): 371–6. doi:10.1016/s0006-291x(78)80052-7. PMID 217377.
4. ↑ "Herpes Prevention". https://congresouniversitariomovil.com/category/herpes-prevention/page/521/.
5. ↑ Schalkwijk, Hanna H.; Snoeck, Robert; Andrei, Graciela (2022-12-01). "Acyclovir resistance in herpes simplex viruses: Prevalence and therapeutic alternatives". Biochemical Pharmacology 206. doi:10.1016/j.bcp.2022.115322. ISSN 0006-2952. https://www.sciencedirect.com/science/article/pii/S0006295222004166.
6. ↑ Labrunie, Thibault; Ducastelle, Sophie; Domenech, Carine; Ader, Florence; Morfin, Florence; Frobert, Emilie (2019-08-01). "UL23, UL30, and UL5 characterization of HSV1 clinical strains isolated from hematology department patients". Antiviral Research 168: 114–120. doi:10.1016/j.antiviral.2019.05.012. ISSN 0166-3542. https://www.sciencedirect.com/science/article/pii/S0166354219300452.

## Further reading

* Yates, MK; Seley-Radtke, KL (February 2019). "The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold.". Antiviral Research 162: 5–21. doi:10.1016/j.antiviral.2018.11.016. PMID 30529089.

* v
* t
* e

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
* Sorivudine

* [[Chemistry:Cytocytosine (Cytarabine|Cytarabine]])

Not TK activated|

* Foscarnet

Other|

* Docosanol
* early protein (Fomivirsen)
* Tromantadine

HPV/MC|

* Imiquimod/Resiquimod
* Podophyllotoxin

Vaccinia|

* assembly: Rifampicin

Poxviridae|

* Methisazone

Hepatitis B (VII)|

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

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

Multiple/general|

| Nucleic acid inhibitors|

* Cidofovir

|

Interferon|

* Interferon alfa 2b
* Peginterferon alfa-2a

Multiple/unknown|

* Ribavirin#/Taribavirin†
* Moroxydine

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

* v
* t
* e

Antiviral drugs: antiretroviral drugs used against HIV (primarily J05)

Entry/fusion inhibitors
(Discovery and development)|

* gp41 (Enfuvirtide (ENF, T-20))
* CCR5 (Maraviroc (MVC)
* Vicriviroc†, Cenicriviroc†, PRO 140†)
* CD4 (Ibalizumab†, UB421§)
* gp120 (Fostemsavir†)

Reverse-transcriptase
inhibitors (RTIs)|

| Nucleoside and
nucleotide (NRTI)|

* Nucleoside analogues/NRTIs: Abacavir (ABC)°#
* Didanosine (ddI)
* Emtricitabine (FTC)°
* Lamivudine (3TC)°#
* Stavudine (d4T)#
* Zidovudine (AZT, ZDV)#
* Amdoxovir†
* Apricitabine†
* Censavudine†
* Elvucitabine†
* Islatravir (EFdA)§
* Racivir†
* Stampidine†
* Zalcitabine (ddC)◊

* Nucleotide analogues/NtRTIs: Tenofovir disoproxil (TDF)°#
* Tenofovir alafenamide (TAF)

|

Non-nucleoside (NNRTI)
(Discovery and development)|

| 1st generation|

* Efavirenz (EFV)°#
* Nevirapine (NVP)#
* Delavirdine (DLV)◊

|

2nd generation|

* diarylpyrimidines
* Etravirine (ETR)
* Rilpivirine (RPV)°
* Doravirine°

Integrase inhibitors
(Integrase strand transfer inhibitors (INSTI))|

* Dolutegravir (DTG)°
* Elvitegravir (EVG)°
* Raltegravir (RAL)°
* BI 224436†
* Cabotegravir†
* Bictegravir (BIC)†
* MK-2048†

Maturation inhibitors|

* Bevirimat†
* BMS-955176§

Protease Inhibitors (PI)
(Discovery and development)|

| 1st generation|

* Amprenavir (APV)◊
* Fosamprenavir (FPV)
* Indinavir (IDV)◊
* Lopinavir (LPV)
* Nelfinavir (NFV)
* Ritonavir (RTV)#
* Saquinavir (SQV)#

|

2nd generation|

* Atazanavir (ATV)°#
* Darunavir (DRV)°#
* Tipranavir (TPV)

Combined formulations|

* Abacavir/lamivudine°#
* Abacavir/dolutegravir/lamivudine°
* Abacavir/lamivudine/zidovudine
* Atazanavir/cobicistat
* Bictegravir/emtricitabine/tenofovir alafenamide
* Darunavir/cobicistat
* Dolutegravir/lamivudine
* Doravirine/lamivudine/tenofovir disoproxil
* Efavirenz/emtricitabine/tenofovir°#
* Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
* Elvitegravir/cobicistat/emtricitabine/tenofovir°
* Emtricitabine/tenofovir alafenamide
* Emtricitabine/rilpivirine/tenofovir alafenamide
* Emtricitabine/rilpivirine/tenofovir°
* Emtricitabine/tenofovir°#
* Lamivudine/raltegravir
* Lamivudine/zidovudine#
* Lopinavir/ritonavir°#

Pharmacokinetic boosters|

* Cobicistat (c)
* Ritonavir (r)#

Experimental agents|

| Uncoating inhibitors|

* TRIM5alpha (gene)

|

Transcription inhibitors|

* Tat antagonists

Translation inhibitors|

* Trichosanthin

Other|

* Abzyme
* BIT225†
* Calanolide A
* Ceragenin
* Cyanovirin-N
* Diarylpyrimidines
* Epigallocatechin gallate (EGCG)
* Foscarnet
* Fosdevirine†
* Griffithsin
* Hydroxycarbamide
* KP-1461†
* Miltefosine
* Portmanteau inhibitors
* Scytovirin
* Seliciclib†
* Synergistic enhancers
* Tre recombinase
* Zinc finger protein transcription factor

Failed agents|

* Aplaviroc
* Atevirdine
* Brecanavir
* Capravirine
* Dexelvucitabine
* Droxinavir
* Lasinavir
* Emivirine
* Lersivirine
* Lodenosine
* Loviride
* Mozenavir
* Palinavir
* Telinavir

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

°DHHS recommended initial regimen options. ◊Formerly or rarely used agent.

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/Nucleoside analogue. Read more

|

Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Nucleoside_analogue&oldid=4357648"
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template