Quantitative structureactivity relationship and molecular. It is the ratelimiting enzyme in the conversion of inosine 5. In this study, a meaningful 3d quantitative structureactivity relationship model comparative molecular field analysis r2 0. Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir showed promising results for use against the newly emerged strain of coronavirus. Taribavirin is an orally available prodrug of ribavirin, a synthetic nucleoside analog of ribofuranose with activity against a wide range of viruses, especially the hepatitis c virus and influenza virus. Ribavirin represents a watersoluble, guanosine nucleoside analogue that mimics other purines, including inosine and adenosine.
Ribavirin is a guanosine analogue that is used in the treatment of paramyxovirus infections. An oi is an infection that occurs more frequently or is more severe in. Hepatitis c virus rnadependent rna polymerase ns5b as a. Choose from 41 different sets of ribavirin flashcards on quizlet.
Although the exact mechanism of its action is unknown, it is thought to interfere with the production andor action of viral dna and rna which are critical to. It is used in combination with interferon for the treatment of chronic hepatitis c. Structural and molecular basis of mismatch correction and. As such it is the concept of linking chemical structure to a chemical property e. Mechanism of action of ribavirin in the treatment of. We determined the crystal structure of the nsp10nsp14 heterodimer by multiwavelength anomalous diffraction mad using the anomalous scattering signal of zinc fig. Structureactivity relationship studies reveal that the 1,2,4triazole ring, carboxamide group and the betadribofuranosyl moiety are pivotal for antiviral activity of this drug. Ribavirin is an antiviral prescription medicine approved by the u. The drugs proposed mechanism of action, as well as pharmacokinetics are discussed, and preclinical toxicity, safety and clinical efficacy studies are. Product information rebetol ribavirin, usp capsules. A study on the biological activity of hepatitis c analogs. Pdf ribavirin, remdesivir, sofosbuvir, galidesivir, and. Webmd provides common contraindications for ribavirin oral. Ribavirin is a synthetic nucleoside analog of ribofuranose with activity against hepatitis c virus and other rna viruses.
Ribavirins later important use against hepatitis c was not even suggested or. Activity relationship qsar and molecular docking are both used to compare the performance of the selected nucleotide inhibitors to their parent nucleotides and ribavirin. We utilized the padel software to extract out various molecular. Antivirals drugs medicinal chemistry linkedin slideshare. Both qsar and molecular docking showed that idx184 is superior compared to ribavirin against mers cov, a result that was also reported. In spite of its limited efficacy and potential side effects, ribavirin is. However, the relationship between urinary ribavirin levels in exposed workers, plasma levels in animal studies, and the specific. The application and mechanism of action of ribavirin in. Clinical use the specific dose and duration of ribavirin therapy depends on the hepatitis c genotype, the patients prior treatment experience, degree of liver fibrosis, and the concomitant medications used for hepatitis c. If the target structure is known, computational chemistry and molecular modelling software packages can be useful in identifying binding site interactions.
When used longterm, ribavirin can cause serious side effects. Ribavirin monotherapy is not effective for treatment of chronic hepatitis c chc virus infection and should not be used alone for this indication. Thus, polyamines contribute to ribavirins antiviral activity. Acyclovir polpharma sa, starogard gdanski, poland and ribavirin. A multicenter survey of retreatment with pegylated interferon plus ribavirin. Recently, we demonstrated that the antiviral activity of ribavirin can result from the ability of a viral rna polymerase to utilize ribavirin triphosphate and to incorporate this nucleotide with reduced specificity, thereby mutagenizing the genome and decreasing the yield. Quantitative structureactivity relationship and molecular docking revealed. Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir against sarscov2 rna dependent rna polymerase rdrp. Guidance on the use of oral ribavirin in the treatment of. The most successful ribavirin derivative to date is the 3carboxamidine derivative of the parent 3carboxamide, first reported in 1973 by j. Curcumin derivatives have been shown to inhibit replication of human influenza a viruses iavs. The optimal dose of ribavirin for chronic hepatitis c. Notable aspects of its structure include a heterocyclic base with only one ring, as opposed to the two rings found in guanine. Ribavirin side effects, dosage, interactions drugs.
Chemical structures of compounds 124, ribavirin, ningnanmycin. Ribavirin is always used in combination with other drugs. Effort to find antivirals for it has focused on bioflavonoids, a plantderived polyphenolic compounds with many potential health benefits. Ribavirin is available in 200 mg, 400 mg, 500 mg, and 600 mg capsules and tablets. Taribavirin is converted into ribavirin, which is incorporated into viral nucleic acid, thereby inhibiting viral rna synthesis, inducing viral genome mutations, and inhibiting normal viral. Ribavirin must be used together with an interferon alfa product such as pegasys, pegintron, sylatron, or intron a to treat chronic hepatitis c ribavirin.
Structure activity relationships sar explore the relationship between a molecules biological activity and the three dimensional structure of the molecule. Ribavirin was rapidly and extensively absorbed following oral administration. Among adults in the western world, chronic hepatitis c chc is the major cause of cirrhosis and the principal indication for liver transplantation. First discovery and stuctureactivity relationship study of. Ribavirin, viramidine and adenosinedeaminasecatalysed. The antiviral activity of ribavirin is ascribed to a combination of different mechanisms 4. Hcv infection is an opportunistic infection oi of hiv. Ribavirin is a prodrug, which when metabolized resembles purine rna nucleotides. As one of the compounds related to ribavirin by structure activity relationship studies, it exhibits in vitro antiviral.
Ribavirin is a guanosine analogue that produces broadspectrum activity against different rna and dna viruses. A study on the biological activity of hepatitis c analogs prediction by qsar an insilco approach m. Ribavirin single and multipledose pharmacokinetic properties in adults with chronic hepatitis c are summarized in table 1. A molecular docking study article pdf available in life sciences 253. This drug shows a similar spectrum of antiviral activity to ribavirin, which is not surprising as it is now known to be a prodrug for ribavirin. Antiviral activity of four types of bioflavonoid against. Dribofuranosyl1h1,2,4 triazole3carboxamide, is a nucleoside analog of molecular weight 244. Synthesis, antiviral activity and structureactivity relationship of 11aryl4. Anemia due to ribavirin may worsen cardiac disease and lead to fatal and nonfatal myocardial infarctions. Ribavirin inhibits the in vitro replication of a wide range of rna and dna viruses, including myxoviruses, paramyxoviruses, arenaviruses. The crystal belongs to the space group p2 1 2 1 2 1, with cell dimensions a 185. Ribavirin, remdesivir, sofosbuvir, galidesivir, and. Idx184 is a superior hcv directacting antiviral drug. Approximately 170 million people worldwide are chronically infected by hepatitis c virus hcv, which can result in progressive hepatic injury and fibrosis, culminating in cirrhosis and endstage liver disease.
Bruker microtofq ii and processed using compass data analysis software. The triazole nucleoside ribavirin rbv, figure1 is used for the treatment of a number of viral infections and may be promising as an anticancer drug. Ribavirin ribavirin have broad spectrum activity, it is purine nucleoside analogue with modified base and dribose sugar moiety properties. The proper care for hepatitis c virus hcv infection with ribavirin elicits sustained responses in the patients treated. Food and drug administration fda for the treatment of chronic hepatitis c virus infection hcv.
Virazole ribavirin for inhalation solution is a sterile, lyophilized powder to be reconstituted for aerosol administration. Quantitative structureactivity relationship qsar parameters. Various types of software were used to judge the validity of the model. The quantitative structureactivity relationship qsar is a mathematical. In addition, ribavirin is available in an oral liquid solution. They find that ribavirin and nucleotide depletion induce polyamine catabolism through spermidinespermine acetyltransferase sat1. Four decades after its discovery this drug still proves useful for the treatment of a. Ribavirin inhibits replication of rna and dna viruses. Chemistry and pharmacokinetics ribavirin is a watersoluble, guanosine nucleoside analogue that mimics other purines including inosine and adenosine 6. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type 2 denv2 in vero cell was evaluated. However, it is not clear whether curcumin and its derivatives can inhibit neuraminidase na of influenza virus. The availability of specific strength depends on the brand of the ribavirin. Ribavirin, a broad spectrum, noninterferoninducing virustatic chemotherapeutic agent, demonstrates activity against a wide range of rna and dna viruses, including the retrovirus known to cause the acquired immune deficiency syndrome.
Dribofuranosyl1h1,2,4triazole3carboxamide and has the following structural formula. Elshemeyquantitative structure activity relationship and molecular docking revealed a potency of antihepatitis c. Quantitative structureactivity relationship qsar and molecular docking are both used to compare the performance of the selected nucleotide inhibitors to their parent nucleotides and ribavirin. Ribavirin is an antiviral drug used offlabel for severe rsv infection individually, hepatitis c infection can be used in conjunction with peginterferon alfa2b or peginterferon alfa2a, and some other viral infections. What is the best tool to find structure activity relationship of sterols and what are general steps to find structure activity relationship. Dengue is a major mosquitoborne disease currently with no effective antiviral or vaccine available. However, due to firstpass metabolism, the absolute bioavailability averaged 64% 44%.
Mechanism of action of ribavirin ribavirin structure and pharmacokinetics. Synthesis and structureactivity relationships of imidazole. Ribavirin is incorporated into viral rna, thereby inhibiting viral rna synthesis, inducing viral genome mutations, and inhibiting normal viral replication. Ribavirin induces polyamine depletion via nucleotide.
Longterm studies in the mouse and rat 18 to 24 months. Toxicity estimation software tool test safer chemicals. Alvarez d, dieterich dt, brau n, moorehead l, ball l, sulkowski ms 2006. Structure activity relationship sar analysis software programs, such as oncologic and multicase mcase, work by analyzing the chemical structure of a compound of unknown toxicity and predicting its likelihood to be a carcinogen based on comparisons to the structures of compounds with known toxicity and programmed chemical and. Antihcv, nucleotide inhibitors, repurposing against covid. Structure activity relationship sar is an approach designed to find relationships between chemical structure or structuralrelated properties and biological activity or target property of studied compounds. Find out what health conditions may be a health risk when taken with ribavirin oral. Zidovudine use but not weightbased ribavirin dosing impacts anaemia during hcv treatment in hivinfected persons. The toxicity estimation software tool test was developed to allow users to easily estimate the toxicity of chemicals using quantitative structure activity relationships qsars methodologies. Quantitative structureactivity relationship and molecular docking. Structure activity relationship studies reveal that the 1,2,4triazole ring, carboxamide group and the betadribofuranosyl moiety are pivotal for antiviral activity of this drug.
Qsars are mathematical models used to predict measures of toxicity from the physical characteristics of the structure of chemicals known as molecular. Virazole, rebetol, copegus is a guanosine analogue fig. Ribavirin is a watersoluble, guanosine nucleoside analogue that mimics other purines including inosine and adenosine. Ribavirin is used in combination with other antiviral medications such as interferon, sofosbuvir to treat chronic longlasting hepatitis c, a viral infection of the liver. Ribavirin icn1229 inhibits denv virus infection in cultured cells, but. Ribavirin icn1229 has strong antiviral activity only when ribavirin is combined with either ifn. One emerging compound is the 3carboxamidine derivative of ribavirin, viramidine previously known as ribamidine6 see figure 3. Hemolytic anemia is the primary clinical toxicity of ribavirin. Its typically prescribed in combination with other medications for up to 24 weeks. This polyamine depletion restricts virus replication, and inhibition of sat1 reduces ribavirins antiviral efficacy. Ribavirin levels are not significantly impacted by mild, moderate, or severe hepatic dysfunction. Ribavirin copegus is available in 200 mg tablets and should be taken with food. Synthesis, antiviral activity and structureactivity relationship of 11.
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