Riamilovir

Last updated
Riamilovir
Triazavirin.svg
Clinical data
Other namesTZV, Triazavirin
ATC code
  • None
Identifiers
  • 2-methylsulfanyl-6-nitro[1,2,4]triazolo[5,1-c] [1,2,4]triazin-7(4H)-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.217.074 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C5H4N6O3S
Molar mass 228.19 g·mol−1
3D model (JSmol)
  • CSc1[nH]n2c(=O)c(nnc2n1)[N+](=O)[O-]
  • InChI=1S/C5H4N6O3S/c1-15-5-6-4-8-7-2(11(13)14)3(12)10(4)9-5/h1H3,(H,6,8,9)
  • Key:IDVQGNMSSHPZSJ-UHFFFAOYSA-N

Riamilovir is a broad-spectrum antiviral drug developed in Russia through a joint effort of Ural Federal University, Russian Academy of Sciences, Ural Center for Biopharma Technologies and Medsintez Pharmaceutical. [1] It has a novel triazolotriazine core, which represents a new structural class of non-nucleoside antiviral drugs. [2]

Contents

The main principle action of triazavirin is to inhibit the synthesis of viral ribonucleic acid (RNA) and the replication of viral genomic fragments through its synthetic analogue to the bases of purine nucleosides. [3] [4] [5]

Uses

It was originally developed as a potential treatment for pandemic influenza strains such as H5N1, and most of the testing that has been done has focused on its anti-influenza activity. [5] [3] [6] [7] [8] However, triazavirin has also been found to have antiviral activity against a number of other viruses including tick-borne encephalitis virus, [4] [9] and is also being investigated for potential application against a lethal influenza infection and secondary bacterial pneumonia following influenza, [10] Lassa fever and Ebola virus disease. [11] [12] [13] [14] [15] Triazavirin has passed clinical trials and has shown antiviral activity against ARVI. [16] [17] [18] [19] In 2020, testing of triazavirin was started against SARS-CoV-2 in Russia, China, and South Africa. [20] [21] [22] [23] [24] [25] [ excessive citations ] The mechanism of action of Triazavirin is still controversial. No experimental biochemical studies on the activity of Triazavirin relating to SARS-CoV-2 or influenza target proteins have so far been published. [26]

In August 2014, the Ministry of Health of Russia issued a registration certificate for triazavirin. [27] The active substance of the drug triazavirin is a new active molecule, [2] and can be dispensed by prescription. The production of triazavirin is carried out at a modern pharmaceutical enterprise LLC "Plant Medsintez". [1] The registration procedure for triazavirin has begun in the Republic of South Africa. [24]

Criticism

The studies of Triazavirin were non-blinded and non-randomized, and included 66 patients only with, with 44 in a control group. [16]

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 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.

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.

<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">Nucleoside analogue</span> Biochemical compound

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.

<span class="mw-page-title-main">Feline viral rhinotracheitis</span> Infectious disease of cats

Feline viral rhinotracheitis (FVR) is an upper respiratory or pulmonary infection of cats caused by Felid alphaherpesvirus 1 (FeHV-1), of the family Herpesviridae. It is also commonly referred to as feline influenza, feline coryza, and feline pneumonia but, as these terms describe other very distinct collections of respiratory symptoms, they are misnomers for the condition. Viral respiratory diseases in cats can be serious, especially in catteries and kennels. Causing one-half of the respiratory diseases in cats, FVR is the most important of these diseases and is found worldwide. The other important cause of feline respiratory disease is feline calicivirus.

<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.

<span class="mw-page-title-main">Resistance mutation (virology)</span> Virus mutation

A resistance mutation is a mutation in a virus gene that allows the virus to become resistant to treatment with a particular antiviral drug. The term was first used in the management of HIV, the first virus in which genome sequencing was routinely used to look for drug resistance. At the time of infection, a virus will infect and begin to replicate within a preliminary cell. As subsequent cells are infected, random mutations will occur in the viral genome. When these mutations begin to accumulate, antiviral methods will kill the wild type strain, but will not be able to kill one or many mutated forms of the original virus. At this point a resistance mutation has occurred because the new strain of virus is now resistant to the antiviral treatment that would have killed the original virus. Resistance mutations are evident and widely studied in HIV due to its high rate of mutation and prevalence in the general population. Resistance mutation is now studied in bacteriology and parasitology.

<span class="mw-page-title-main">Herpes</span> Viral disease caused by herpes simplex viruses

Herpes simplex, often known simply as herpes, is a viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are oral herpes and genital herpes, though other forms also exist.

A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, intracellular bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.

<span class="mw-page-title-main">FGI-104</span> Chemical compound

FGI-104 is the name of an experimental broad-spectrum antiviral drug, with activity against a range of viruses including hepatitis B, hepatitis C, HIV, Ebola virus, and Venezuelan equine encephalitis virus.

<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">Ebola virus disease treatment research</span>

There is a cure for the Ebola virus disease that is currently approved for market the US government has inventory in the Strategic National Stockpile. For past and current Ebola epidemics, treatment has been primarily supportive in nature.

<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">NITD008</span> Chemical compound

NITD008 is an antiviral drug classified as an adenosine 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. 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.

<span class="mw-page-title-main">Convalescent plasma</span> Blood plasma from disease survivor

Convalescent plasma is the blood plasma collected from a survivor of an infectious disease. This plasma contains antibodies specific to a pathogen and can be used therapeutically by providing passive immunity when transfusing it to a newly infected patient with the same condition. Convalescent plasma can be transfused as it has been collected or become the source material for hyperimmune serum or anti-pathogen monoclonal antibodies; the latter consists exclusively of IgG, while convalescent plasma also includes IgA and IgM. Collection is typically achieved by apheresis, but in low-to-middle income countries, the treatment can be administered as convalescent whole blood.

<span class="mw-page-title-main">Molnupiravir</span> Antiviral medication

Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses. It is used to treat COVID‑19 in those infected by SARS-CoV-2. It is taken by mouth.

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

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.

<span class="mw-page-title-main">S416</span> Chemical compound

S416 (GTPL-11164) is a drug which acts as a selective inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme is involved in the synthesis of pyrimidine nucleosides in the body, which are required for the synthesis of DNA and RNA. This is an important rate-limiting step in the replication of viruses, and so DHODH inhibitors may have applications as broad-spectrum antiviral drugs. In tests in vitro, S416 was found to have antiviral activity against a range of pathogenic RNA viruses including influenza, Zika virus, Ebola virus and SARS-CoV-2.

A therapeutic interfering particle is an antiviral preparation that reduces the replication rate and pathogenesis of a particular viral infectious disease. A therapeutic interfering particle is typically a biological agent (i.e., nucleic acid) engineered from portions of the viral genome being targeted. Similar to Defective Interfering Particles (DIPs), the agent competes with the pathogen within an infected cell for critical viral replication resources, reducing the viral replication rate and resulting in reduced pathogenesis. But, in contrast to DIPs, TIPs are engineered to have an in vivo basic reproductive ratio (R0) that is greater than 1 (R0>1). The term "TIP" was first introduced in 2011 based on models of its mechanism-of-action from 2003. Given their unique R0>1 mechanism of action, TIPs exhibit high barriers to the evolution of antiviral resistance and are predicted to be resistance proof. Intervention with therapeutic interfering particles can be prophylactic (to prevent or ameliorate the effects of a future infection), or a single-administration therapeutic (to fight a disease that has already occurred, such as HIV or COVID-19). Synthetic DIPs that rely on stimulating innate antiviral immune responses (i.e., interferon) were proposed for influenza in 2008 and shown to protect mice to differing extents but are technically distinct from TIPs due to their alternate molecular mechanism of action which has not been predicted to have a similarly high barrier to resistance. Subsequent work tested the pre-clinical efficacy of TIPs against HIV, a synthetic DIP for SARS-CoV-2 (in vitro), and a TIP for SARS-CoV-2 (in vivo).

References

  1. 1 2 "Triazaverin Is Officially Recommended". www.medsintez.com. Retrieved 2021-02-25.
  2. 1 2 Rusinov VL, Sapozhnikova IM, Ulomskii EN, Medvedeva NR, Egorov VV, Kiselev OI, et al. (2015). "Nucleophilic substitution of nitro group in nitrotriazolotriazines as a model of potential interaction with cysteine-containing proteins". Chemistry of Heterocyclic Compounds. 51 (3): 275–280. doi: 10.1007/s10593-015-1695-4 . S2CID   83702396.
  3. 1 2 Karpenko I, Deev S, Kiselev O, Charushin V, Rusinov V, Ulomsky E, et al. (May 2010). "Antiviral properties, metabolism, and pharmacokinetics of a novel azolo-1,2,4-triazine-derived inhibitor of influenza A and B virus replication". Antimicrobial Agents and Chemotherapy. 54 (5): 2017–2022. doi:10.1128/AAC.01186-09. PMC   2863629 . PMID   20194696.
  4. 1 2 Loginova SI, Borisevich SV, Rusinov VL, Ulomskiĭ UN, Charushin VN, Chupakhin ON (2014). "[Investigation of Triazavirin antiviral activity against tick-borne encephalitis pathogen in cell culture]". Antibiotiki i Khimioterapiia (in Russian). 59 (1–2): 3–5. PMID   25051708.
  5. 1 2 Loginova SI, Borisevich SV, Maksimov VA, Bondarev VP, Kotovskaia SK, Rusinov VL, et al. (2007). "[Investigation of triazavirin antiviral activity against influenza A virus (H5N1) in cell culture]". Antibiotiki i Khimioterapiia (in Russian). 52 (11–12): 18–20. PMID   19275052.
  6. ↑ Kiselev OI, Deeva EG, Mel'nikova TI, Kozeletskaia KN, Kiselev AS, Rusinov VL, et al. (2012). "[A new antiviral drug Triazavirin: results of phase II clinical trial]". Voprosy Virusologii (in Russian). 57 (6): 9–12. PMID   23477247.
  7. ↑ Kasianenko KV, Lvov NI, Maltsev OV, Zhdanov KV (9 October 2019). "Nucleoside analogues for the treatment of influenza: History and experience". Journal of Infectology (in Russian). 11 (3): 20–26. doi: 10.22625/2072-6732-2019-11-3-20-26 . S2CID   241604614.
  8. ↑ Sologub TV, Tokin II, Midikari AS, Tsvetkov VV (2017). "A comparative efficacy and safety of using antiviral drugs in therapy of patients with influenza". Infekcionnye Bolezni (in Russian). 15 (3): 25–32. doi:10.20953/1729-9225-2017-3-25-32.
  9. ↑ Loginova SY, Borisevich SV, Rusinov VL, Ulomsky EN, Charushin VN, Chupakhin ON, et al. (2015). "[Investigation of Therapeutic Efficacy of Triazavirin Against Experimental Forest-Spring Encephalitis on Albino Mice]". Antibiotiki i Khimioterapiia (in Russian). 60 (7–8): 11–13. PMID   26863736.
  10. ↑ Leneva IA, Falynskova IN, Makhmudova NR, Glubokova EA, Kartashova NP, Leonova EI, et al. (2018-02-22). "Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice". Microbiology Independent Research Journal. 4 (1). doi: 10.18527/2500-2236-2017-4-1-52-57 .
  11. ↑ "Target: Ebola". Pravda. 2014-12-22. Retrieved 18 January 2015.
  12. ↑ "Yekaterinburg pharmacies to sell domestic antiviral drug". Yekaterinburg News Reports. 6 January 2015. Archived from the original on 18 January 2015. Retrieved 18 January 2015.
  13. ↑ Cox S (2014-10-17). "Ebola crisis: Vaccine 'too late' for outbreak. BBC News, 17 October 2014". BBC News.
  14. ↑ Bora K (12 November 2014). "Russia Will Begin Testing Triazavirin, Used For Lassa Fever, And Other Drugs On Ebola: Health Ministry". International Business Times.
  15. ↑ Kezina D (12 November 2014). "New antiviral drug from Urals will help fight Ebola and other viruses". Russia Beyond the Headlines.
  16. 1 2 Tikhonova EP, Kuz'mina TY, Andronova NV, Tyushevskaya OA, Elistratova TA, Kuz'min AE (2018-04-15). "Study of effectiveness of antiviral drugs (umifenovir, triazavirin) against acute respiratory viral infections". Kazan Medical Journal (in Russian). 99 (2): 215–223. doi: 10.17816/KMJ2018-215 . ISSN   2587-9359.
  17. ↑ Verevshchikov VK, Shemyakina EK, Sabitov AU, Khamanova YB (2019). "The Possibilities of Etiotropic Therapy for Influenza and ARVI with Taking into Account the Period of Hospitalization and the Risk of Developing Secondary Complications". Antibiotics and Chemotherapy. Retrieved 2021-02-25.
  18. ↑ Lioznov DA, Tokin II, Zubkova TG, Sorokin PV (December 2020). "[The practice of using a domestic antiviral drug in the etiotropic therapy of acute respiratory viral infection]". Terapevticheskii Arkhiv (in Russian). 92 (12): 160–164. doi: 10.26442/00403660.2020.12.200427 . PMID   33720589.
  19. ↑ Verevshchikov VK, Shemyakina EK, Sabitov AU, Batskalevich NA (2018). "Modern Etiotropic Therapy of Influenza and ARVI in Adult Patients with Premorbid Pathology". Antibiotics and Chemotherapy. Retrieved 2021-02-25.
  20. ↑ Jamshaid U (4 February 2020). "China Testing Russia's Triazavirin As Coronavirus Treatment". Russian Health Ministry. Urdupoint.
  21. ↑ Phiri C (5 February 2020). "China Tests Russian Antiviral Drug Which Might Treat Coronavirus As Moscow Warns Of Possible 'Mass Outbreak'". Zambia Reports. Archived from the original on 5 February 2020. Retrieved 11 February 2020.
  22. ↑ Wu X, Yu K, Wang Y, Xu W, Ma H, Hou Y, et al. (October 2020). "Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019: A Pilot Randomized Controlled Trial". Engineering. 6 (10): 1185–1191. doi: 10.1016/j.eng.2020.08.011 . PMC   7476906 . PMID   32923016. S2CID   221520816.
  23. ↑ Brandt K. "SA study to trial antiviral Triazavirin as COVID-19 treatment". ewn.co.za. Retrieved 2021-02-25.
  24. 1 2 "Discussion on Russia's antiviral drug Triazavirin". SABC News. 21 January 2021 – via YouTube.
  25. ↑ Sabitov AU, Belousov VV, Edin AS, Oleinichenko EV, Gladunova EP, Tikhonova EP, et al. (21 November 2020). "Practical Experience of Using Riamilovir in Treatment of Patients with Moderate COVID-19". Antibiotiki i Khimioterapiya. 65 (7–8): 27–30. doi: 10.37489/0235-2990-2020-65-7-8-27-30 . S2CID   229508119.
  26. ↑ Chupakhin ON, Rusinov VL, Varaksin MV, Ulomskiy EN, Savateev KV, Butorin II, et al. (November 2022). "Triazavirin-A Novel Effective Antiviral Drug". International Journal of Molecular Sciences. 23 (23): 14537. doi: 10.3390/ijms232314537 . PMC   9738222 . PMID   36498864.
  27. ↑ "Triazavirin (Riamilovir)". State Register of Medicines of the Russian Federation (in Russian).
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.