NITD008

Last updated
NITD008
NITD008.svg
Clinical data
Trade names NITD008
Identifiers
  • (2R,3R,4R,5R)-2-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C13H14N4O4
Molar mass 290.279 g·mol−1
3D model (JSmol)
  • C#C[C@]1([C@@H]([C@H](O[C@H]1N2C=CC3=C2N=CN=C3N)CO)O)O
  • InChI=1S/C13H14N4O4/c1-2-13(20)9(19)8(5-18)21-12(13)17-4-3-7-10(14)15-6-16-11(7)17/h1,3-4,6,8-9,12,18-20H,5H2,(H2,14,15,16)/t8-,9-,12-,13-/m1/s1
  • Key:NKRAIOQPSBRMOV-NRMKKVEVSA-N

NITD008 is an antiviral drug classified as an adenosine analog (a type of nucleoside analog). It was developed as a potential treatment for flavivirus infections and shows broad spectrum antiviral activity against many related viruses such as dengue virus, West Nile virus, yellow fever virus, Powassan virus, hepatitis C virus, Kyasanur Forest disease virus, Omsk hemorrhagic fever virus, and Zika virus. [1] [2] [3] However, NITD008 proved too toxic in pre-clinical animal testing to be suitable for human trials, but it continues to be used in research to find improved treatments for emerging viral diseases. [4]

See also

Related Research Articles

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural viricides are produced by some plants such as eucalyptus and Australian tea trees.

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

Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building blocks of RNA (and its derivative deoxyadenosine is a building block of DNA), which are essential for all life. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. Adenosine is used as an intravenous medication for some cardiac arrhythmias.

<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.

Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses.

<i>Dengue virus</i> Species of virus

Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Four serotypes of the virus have been found, a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, scientists' understanding of dengue virus may be simplistic as, rather than distinct antigenic groups, a continuum appears to exist. This same study identified 47 strains of dengue virus. Additionally, coinfection with and lack of rapid tests for Zika virus and chikungunya complicate matters in real-world infections.

<span class="mw-page-title-main">Rimantadine</span> Drug used to treat influenzavirus A infection

Rimantadine is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Rimantadine can mitigate symptoms, including fever. Both rimantadine and the similar drug amantadine are derivates of adamantane. Rimantadine is found to be more effective than amantadine because when used the patient displays fewer symptoms. Rimantadine was approved by the Food and Drug Administration (FDA) in 1994.

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

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">Entecavir</span>

Entecavir (ETV), sold under the brand name Baraclude, is an antiviral medication used in the treatment of hepatitis B virus (HBV) infection. In those with both HIV/AIDS and HBV antiretroviral medication should also be used. Entecavir is taken by mouth as a tablet or solution.

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

Umifenovir, sold under the brand name Arbidol, is an antiviral medication for the treatment of influenza and COVID infections used in Russia and China. The drug is manufactured by Pharmstandard. It is not approved by the U.S. Food and Drug Administration (FDA) for the treatment or prevention of influenza.

Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV). NNRTIs inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV. RT is one of the most popular targets in the field of antiretroviral drug development.

Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs.

<span class="mw-page-title-main">Favipiravir</span> Experimental antiviral drug with potential activity against RNA viruses

Favipiravir, sold under the brand name Avigan among others, is an antiviral medication used to treat influenza in Japan. It is also being studied to treat a number of other viral infections, including SARS-CoV-2. Like the experimental antiviral drugs T-1105 and T-1106, it is a pyrazinecarboxamide derivative.

<span class="mw-page-title-main">Galidesivir</span> Antiviral drug

Galidesivir is an antiviral drug, an adenosine analog. It was developed by BioCryst Pharmaceuticals with funding from NIAID, originally intended as a treatment for hepatitis C, but subsequently developed as a potential treatment for deadly filovirus infections such as Ebola virus disease and Marburg virus disease, as well as Zika virus. Currently, galidesivir is under phase 1 human trial in Brazil for coronavirus.

<span class="mw-page-title-main">Carbocyclic nucleoside</span> Class of chemical compounds

Carbocyclic nucleosides are nucleoside analogues in which a methylene group has replaced the oxygen atom of the furanose ring. These analogues have the nucleobase attached at a simple alkyl carbon rather than being part of a hemiaminal ether linkage. As a result, they have increased chemical stability. They also have increased metabolic stability because they are unaffected by phosphorylases and hydrolases that cleave the glycosidic bond between the nucleobase and furanose ring of nucleosides. They retain many of the biological properties of the original nucleosides with respect to recognition by various enzymes and receptors.

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

Islatravir is an investigational drug for the treatment of HIV infection. It is classified as a nucleoside reverse transcriptase translocation inhibitor (NRTTI). Merck is developing a subdermal drug-eluting implant to administer islatravir.

<span class="mw-page-title-main">MK-608</span> Chemical compound

MK-608 is an antiviral drug, an adenosine analog. It was originally developed by Merck & Co. as a treatment for hepatitis C, but despite promising results in animal studies, it was ultimately unsuccessful in clinical trials. Subsequently it has been widely used in antiviral research and has shown activity against a range of viruses, including Dengue fever, tick-borne encephalitis virus, poliovirus, and most recently Zika virus, in both in vitro and animal models. Since it has already failed in human clinical trials previously, it is unlikely MK-608 itself will be developed as an antiviral medication, but the continuing lack of treatment options for these emerging viral diseases means that much research continues using MK-608 and related antiviral drugs.

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

Mericitabine (RG-7128) is an antiviral drug, a deoxycytidine analog. It was developed as a treatment for hepatitis C, acting as a NS5B RNA polymerase inhibitor, but while it showed a good safety profile in clinical trials, it was not sufficiently effective to be used as a stand-alone agent. However mericitabine has been shown to boost the efficacy of other antiviral drugs when used alongside them, and as most modern treatment regimens for hepatitis C use a combination therapy of several antiviral drugs, clinical trials have continued to see if it can form a part of a clinically useful drug treatment program.

<span class="mw-page-title-main">CMX521</span>

CMX521 is an antiviral drug discovered by Chimerix, which was developed for the treatment of norovirus, though it also shows efficacy against related viral diarrheas such as rotovirus and some sapoviruses, astroviruses and adenoviruses. It is a nucleoside analogue which acts as an inhibitor of viral RNA-dependant RNA polymerase.

<span class="mw-page-title-main">GS-441524</span>

GS-441524 is a nucleoside analogue antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, and has a half-life of around 24 hours in human patients. Remdesivir and GS-441524 were both found to be effective in vitro against feline coronavirus strains responsible for feline infectious peritonitis (FIP), a lethal systemic disease affecting domestic cats. Remdesivir was never tested in cats, but GS-441524 has been found to be effective treatment for FIP and is widely used despite no official FDA approval due to Gilead's refusal to license this drug for veterinary use. An isopropylester pro-drug of GS-441524 - Obeldesivir has been developed by GILEAD Sciences and is in Phase III clinical trials. A deuterated form has been developed by Vigonvita Life Sciences and is also in Phase III clinical trials.

<span class="mw-page-title-main">Sangivamycin</span>

Sangivamycin is a natural product originally isolated from Streptomyces rimosus, which is a nucleoside analogue. It acts as an inhibitor of protein kinase C. It has antibiotic, antiviral and anti-cancer properties and has been investigated for various medical applications, though never approved for clinical use itself. However, a number of related derivatives continue to be researched.

References

  1. Yin Z, Chen YL, Schul W, Wang QY, Gu F, Duraiswamy J, et al. (December 2009). "An adenosine nucleoside inhibitor of dengue virus". Proceedings of the National Academy of Sciences of the United States of America. 106 (48): 20435–9. Bibcode:2009PNAS..10620435Y. doi: 10.1073/pnas.0907010106 . PMC   2787148 . PMID   19918064.
  2. Lo MK, Shi PY, Chen YL, Flint M, Spiropoulou CF (June 2016). "In vitro antiviral activity of adenosine analog NITD008 against tick-borne flaviviruses". Antiviral Research. 130: 46–9. doi:10.1016/j.antiviral.2016.03.013. PMC   5096641 . PMID   27016316.
  3. Deng YQ, Zhang NN, Li CF, Tian M, Hao JN, Xie XP, et al. (October 2016). "Adenosine Analog NITD008 Is a Potent Inhibitor of Zika Virus". Open Forum Infectious Diseases. 3 (4): ofw175. doi: 10.1093/ofid/ofw175 . PMC   5063548 . PMID   27747251.
  4. Nelson J, Roe K, Orillo B, Shi PY, Verma S (October 2015). "Combined treatment of adenosine nucleoside inhibitor NITD008 and histone deacetylase inhibitor vorinostat represents an immunotherapy strategy to ameliorate West Nile virus infection". Antiviral Research. 122: 39–45. doi:10.1016/j.antiviral.2015.07.008. PMC   4853296 . PMID   26225754.