 | |
| Legal status | |
|---|---|
| Legal status |
|
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C32H38N4O6S |
| Molar mass | 606.7 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
TMC-647055 is an experimental antiviral drug which was developed as a treatment for hepatitis C, and is in clinical trials as a combination treatment with ribavirin and simeprevir. It acts as a NS5b polymerase inhibitor. [1] [2] [3]
The hepatitis C virus (HCV) is a small, enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer and lymphomas in humans.
Taribavirin is an antiviral drug in Phase III human trials, but not yet approved for pharmaceutical use. It is a prodrug of ribavirin, active against a number of DNA and RNA viruses. Taribavirin has better liver-targeting than ribavirin, and has a shorter life in the body due to less penetration and storage in red blood cells. It is expected eventually to be the drug of choice for viral hepatitis syndromes in which ribavirin is active. These include hepatitis C and perhaps also hepatitis B and yellow fever.
PSI-6130 is an experimental treatment for hepatitis C. PSI-6130 is a member of a class of antiviral drugs known as nucleoside polymerase inhibitors that was created by chemist Jeremy L. Clark. Specifically, PSI-6130 inhibits the hepatitis C virus RNA dependant RNA polymerase called NS5B.
Setrobuvir was an experimental drug candidate for the treatment of hepatitis C that was discovered at Anadys Pharmaceuticals, which was acquired by Roche in 2011; Roche terminated development in July 2015. It was in Phase IIb clinical trials, used in combination with interferon and ribavirin, targeting hepatitis C patients with genotype 1.
Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken by mouth.
Simeprevir, sold under the brand name Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.
Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. After completing Phase III clinical trials, on February 10, 2014, Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination tablet for genotype 1 hepatitis C. The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin.
Deleobuvir was an experimental drug for the treatment of hepatitis C. It was being developed by Boehringer Ingelheim. It is a non-nucleoside hepatitis C virus NS5B polymerase inhibitor. Deleobuvir was tested in combination regimens with pegylated interferon and ribavirin, and in interferon-free regimens with other direct-acting antiviral agents including faldaprevir.
Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. Several crystal structures of NS5B polymerase in several crystalline forms have been determined based on the same consensus sequence BK. The structure can be represented by a right hand shape with fingers, palm, and thumb. The encircled active site, unique to NS5B, is contained within the palm structure of the protein. Recent studies on NS5B protein genotype 1b strain J4's (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. De-novo adds necessary primers for initiation of RNA replication.
Beclabuvir is an antiviral drug for the treatment of hepatitis C virus (HCV) infection that has been studied in clinical trials. In February 2017, Bristol-Myers Squibb began sponsoring a post-marketing trial of beclabuvir, in combination with asunaprevir and daclatasvir, to study the combination's safety profile with regard to liver function. From February 2014 to November 2016, a phase II clinical trial was conducted on the combination of asunaprevir/daclatasvir/beclabuvir on patients infected with both HIV and HCV. Furthermore, a recent meta-analysis of six published six clinical trials showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, asunaprevir, and beclabuvir irrespective of ribavirin use, prior interferon-based therapy, or restriction on noncirrhotic patients, IL28B genotype, or baseline resistance-associated variants
Filibuvir was a non-nucleoside orally available NS5B inhibitor developed by Pfizer for the treatment of hepatitis C. It binds to the non-catalytic Thumb II allosteric pocket of NS5B viral polymerase and causes a decrease in viral RNA synthesis. It is a potent and selective inhibitor, with a mean IC50 of 0.019 μM against genotype 1 polymerases. Several filibuvir-resistant mutations have been identified, M423 being the most common that occurred after filibuvir monotherapy. It was intended to be taken twice-daily.
Daclatasvir/sofosbuvir is a two-drug combination for the treatment of hepatitis C. It is given as a single daily pill containing daclatasvir, a viral NS5A inhibitor, and sofosbuvir, a nucleotide inhibitor of the viral RNA polymerase NS5B.
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.
Nonstructural protein 5A (NS5A) inhibitors are direct acting antiviral agents (DAAs) that target viral proteins, and their development was a culmination of increased understanding of the viral life cycle combined with advances in drug discovery technology. However, their mechanism of action is complex and not fully understood. NS5A inhibitors were the focus of much attention when they emerged as a part of the first curative treatment for hepatitis C virus (HCV) infections in 2014. Favorable characteristics have been introduced through varied structural changes, and structural similarities between NS5A inhibitors that are clinically approved are readily apparent. Despite the recent introduction of numerous new antiviral drugs, resistance is still a concern and these inhibitors are therefore always used in combination with other 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.
Narlaprevir, is an inhibitor of NS3/4A serine protease, intended for the treatment of chronic hepatitis C caused by genotype 1 virus in combination with other antiviral drugs.
Danoprevir (INN) is an orally available 15-membered macrocyclic peptidomimetic inhibitor of NS3/4A HCV protease. It contains acylsulfonamide, fluoroisoindole and tert-butyl carbamate moieties. Danoprevir is a clinical candidate based on its favorable potency profile against multiple HCV genotypes 1–6 and key mutants (GT1b, IC50 = 0.2–0.4 nM; replicon GT1b, EC50 = 1.6 nM). Danoprevir has been evaluated in an open-label, single arm clinical trial in combination with ritonavir for treating COVID-19 and favourably compared to lopinavir/ritonavir in a second trial.
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.
IDX-184 is an antiviral drug which was developed as a treatment for hepatitis C, acting as a NS5B RNA polymerase inhibitor. While it showed reasonable effectiveness in early clinical trials it did not progress past Phase IIb. However research using this drug has continued as it shows potentially useful activity against other emerging viral diseases such as Zika virus, and coronaviruses including MERS, and SARS-CoV-2.
 | This antiinfective drug article is a stub. You can help Wikipedia by expanding it. |
