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Trade names | NITD008 |
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Formula | C13H14N4O4 |
Molar mass | 290.279 g·mol−1 |
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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]
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 a 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 virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.
Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. Among the viral hemorrhagic fevers it is sometimes used for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infection but should not be used for Ebola or Marburg infections. Ribavirin is taken orally or inhaled. Despite widespread usage, since the 2010s it has faced scrutiny for a lack of efficacy in treating viral infections it has historically been prescribed for.
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.
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, and a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, the mainstream scientific community's 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.
Vidarabine or 9-β-D-arabinofuranosyladenine (ara-A) is an antiviral drug which is active against herpes simplex and varicella zoster viruses.
Entecavir, sold under the brand name Baraclude, is an antiviral medication used in the treatment of hepatitis B virus infection. In those with both HIV/AIDS and hepatitis B virus antiretroviral medication should also be used. Entecavir is taken by mouth as a tablet or solution.
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. They are related to nucleic acid analogues.
Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.
Mosquito-borne diseases or mosquito-borne illnesses are diseases caused by bacteria, viruses or parasites transmitted by mosquitoes. Nearly 700 million people contract mosquito-borne illnesses each year, resulting in more than a million deaths.
Zika virus is a member of the virus family Flaviviridae. It is spread by daytime-active Aedes mosquitoes, such as A. aegypti and A. albopictus. Its name comes from the Ziika Forest of Uganda, where the virus was first isolated in 1947. Zika virus shares a genus with the dengue, yellow fever, Japanese encephalitis, and West Nile viruses. Since the 1950s, it has been known to occur within a narrow equatorial belt from Africa to Asia. From 2007 to 2016, the virus spread eastward, across the Pacific Ocean to the Americas, leading to the 2015–2016 Zika virus epidemic.
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.
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.
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.
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.
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.
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.
Non-structural protein 5B (NS5B) inhibitors are a class of direct-acting antivirals widely used in the treatment of chronic hepatitis C. Depending on site of action and chemical composition, NS5B inhibitors may be categorized into three classes—nucleoside active site inhibitors (NIs), non-nucleoside allosteric inhibitors, and pyrophosphate analogues. Subsequently, all three classes are then subclassified. All inhibit RNA synthesis by NS5B but at different stages/sites resulting in inability of viral RNA replication. Expression of direct-acting NS5B inhibitors does not take place in cells that are not infected by hepatitis C virus, which seems to be beneficial for this class of drugs.
GS-6620 is an antiviral drug which is a nucleotide analogue. It was developed for the treatment of Hepatitis C but while it showed potent antiviral effects in early testing, it could not be successfully formulated into an oral dosage form due to low and variable absorption in the intestines which made blood levels unpredictable. It has however continued to be researched as a potential treatment for other viral diseases such as Ebola virus disease.
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.
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.