Tracking the relevant researches of CADD drug development against COVID-19
Producing a broad-spectrum activity against several RNA and DNA viruses, Ribavirin is a synthetic guanosine nucleoside and antiviral agent that interferes with the synthesis of viral mRNA. It is primarily indicated for use in treating hepatitis C and viral hemorrhagic fevers. HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients. It is reported that ribavirin might be only effective in early stages of viral hemorrhagic fevers including Lasser fever, Crimean-Congo hemorrhagic fever, Venezuelan hemorrhagic fever, and Hantavirus infection. Ribavirin is a prodrug that is metabolized into nucleoside analogs that blocks viral RNA synthesis and viral mRNA capping. Before the development of newer drugs, ribavirin andPeginterferon alfa-2a/Peginterferon alfa-2bdual therapy was considered the first-generation and standard antiviral treatment. The dual therapy was administered for 48 weeks in patients with genotype 1, 4, 5, and 6, and 24 weeks in patients with genotype 2 and 3. Newer drugs developed as Hepatitis C viral infection treatments can be used to reduce or eliminate the use of ribavirin, which are associated with serious adverse effects. They also improve therapeutic efficacy in patients with failedPeginterferon alfa-2a/Peginterferon alfa-2band ribavirin-based therapy. The potential use of ribavirin as a treatment for acute myeloid leukemia is currently under investigation.According to 2017 American Association for the Study of Liver Diseases (AASLD) and 2015 consensus guidelines from the Canadian Association for the Study of the Liver (CASL), ribavirin is typically used as an adjunct therapy to various first-line and second-line combination therapies recommended for each genotypes. Ribavirin is added to decrease relapse rates by accelerating viral clearance early in the treatment course. When used to treat Hepatitis C virus (HCV) infections, it is always used as a part of combination therapies as ribavirin monotherapy is not efficacious in the treatment of chronic hepatitis C infection. Additionally, including ribavirin in the regimen can increase the risk of anemia.In HCV genotye 1/2/3/4/5/6 patients, ribavirin can be used in combination therapy involvingDaclatasvirandSofosbuvir, Eplusa (Sofosbuvir,Velpatasvir), Harvoni (Sofosbuvir,Ledipasvir),SimeprevirandSofosbuvir, Viekira Pak (Ombitasvir,Paritaprevir,Ritonavir,Dasabuvir), Technivie (Ritonavir,Ombitasvir,Paritaprevir) and Zepatier (Elbasvir,Grazoprevir). Addition of weight-based ribavirin to Technivie therapy increased sustained virologic response after 12 weeks of daily therapy (SVR12) from 90% to 97% in patients with HCV genotype 1a and 90.9% to 100% in HCV genotype 4 patients. Zepatier therapy along with ribavirin improved SVR in HCV genotype 5 patients. Combination therapy of ribavirin andPeginterferon alfa-2aresults in the SVR of 44% in patients with genotype 1 infection and 70% in patients with genotype 2-6. The inclusion of ribavirin in the combination therapies depend on individual patient's profile, for example if HCV genotype 3 patient has a Y93H genetic variant and compensated cirrhosis. [DrugBank]
Inosine-5'-monophosphate dehydrogenase 1 (Humans); Inosine-5'-monophosphate dehydrogenase 2 (Humans); RNA-directed RNA polymerase L (HPIV-2); RNA-directed RNA polymerase catalytic subunit (Influenza A virus (strain A/Beijing/11/1956 H1N1)); Genome polyprotein (DENV-2) [DrugBank]
Ribavirin mediates direct antiviral activity against a number of DNA and RNA viruses by increasing the mutation frequency in the genomes of several RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material. The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to its resemblence to building blocks of the RNA molecules. [DrugBank]
Tips: Click on the link to jump to the 'SwissTargetPrediction' webserver. Select the species of 'Homo sapiens', and then paste the SMILES of Ribavirin in the SMILES input box.
Tips: Click on the link to jump to the 'CB-Dock' webserver. Upload the structure file of target predicted by 'SwissTargetPrediction' and the 2D/3D structure file of Ribavirin to perform blind docking.