Hepatitis C is a viral infection that is caused by the hepatitis C virus (HCV) and mainly targets the 'liver', making acute and chronic infections. Our firm strives to improve the development of HCV vaccines and therapeutics and offers various services that speed up the process from bench to bedside.
Introduction to Hepatitis C
Hepatitis C is a liver propagating viral infection that is caused by the hepatitis C virus (HCV). Discovered as an enveloped positive sense single stranded RNA virus, it belongs to the Flaviviridae family. Like most of its kin, it primarily spreads via infected blood. Sharing needles while drug injecting, accidental needle sticks in health care settings or unscreened blood transfusions are other prevalent methods.
Acute hepatitis C usually manifests itself with mild or even asymptomatic symptoms which makes early detection tricky. However, in 75-85% of cases, the HCV virus stays insistent which means chronic HCV is unaddressed. Chronic HCV when untreated can lead to liver damage that can, but is not limited to cirrhosis and hepatocellular carcinoma. An estimated 80-160 million people worldwide are suffering from chronic HCV infection emphasizing how significant of a concern it is.
Fig.1 Hepatitis C virus (HCV) life cycle. (Manns M. P., et al., 2017)
Vaccine Development for Hepatitis C
Subunit Vaccines
These vaccines are constructed by making use of specific viral proteins such as the E1 and E2 envelope glycoproteins to elicit an immune response. For example, some researchers focus on the development of recombinant HCV envelope proteins that have demonstrated potential in preclinical tests.
Virus-Like Particles (VLPs)
VLPs are devoid of a viral genome, but they possess a structure which enables the body to elicit an immune response against it. VLP-based vaccines have been previously tested and it has been shown that they could be able to generate neutralizing antibodies specific for HCV.
DNA and RNA-Based Vaccines
These DNA and RNA based vaccines are the most advanced technologies that involves the direct introduction of genetic materials that encode the specific HCV antigens. As a result, VLPs based vaccines are expected to generate powerful immune responses due to the utilization of this novel technology.
Therapeutics Development for Hepatitis C
The development of direct-acting antivirals (DAAs) greatly improved HCV therapeutics. These agents focus on several viral proteins and effectively eradicate the virus. Examples include:
- NS3/4A Protease Inhibitors: Grazoprevir and paritaprevir are a class of drugs that inhibit the NS3/4A protease and thus interrupt the process of viral replication.
- NS5B Polymerase Inhibitors: Sofosbuvir and velpatasvir are nucleotide analogs which inhibit the viral RNA polymerase and decrease the rate of viral replication.
- NS5A Inhibitors: Ledipasvir and daclatasvir act on the NS5A protein which assists in the viral replication and assembly process.
Table 1 Selected directly acting antiviral agents and host targeting agents in the pipeline. (Morozov V. A., et al., 2018)
|
Drugs name |
Target/active site |
Company |
Phase |
| NS3/4A protease inhibitors |
| Vaniprevir (MK-7009) |
Active site/macrocyclic |
Merck |
III |
| Voxilaprevir GS-9857 |
Active site |
Gilead |
III |
| Glecaprevir (ABT-493) |
Active site |
Abbvie |
III |
| IDX21437 |
Active site |
Idenix |
II |
| Sovaprevir (ACH-1625) |
Active site/macrocyclic? |
Achillion |
II |
| Nucleoside analog NS5B polymerase inhibitors (NI) |
| MK-3682 (formerly IDX20963) |
Active site |
Merck |
II |
| ACH-3422 |
Active site |
Achillion/Janssen |
II |
| Non- Nucleoside analog NS5B polymerase inhibitors (NNI) |
| Beclabuvir (BMS-791325) |
NNI site 1/Thumb 1 |
Bristol-Myers Squib |
III |
| Setrobuvir (ANA598) |
NNI site 4?/palm 1 |
Anadys/Roche |
II |
| NS5A inhibitors |
| BMS-824393 |
NS5A protein |
Bristol-Myers Squibb |
II |
| PPI-461 |
NS5A protein |
Presidio |
II |
| PPI-668 |
NS5A protein |
Presidio |
II |
| Pibrentasvir (ABT-530) |
NS5A protein |
Abbvie |
III |
| ACH-2928 |
NS5A protein |
Achillion |
I |
| Ruzasvir (MK-8408) |
NS5A protein |
Merck |
II |
| Host targeting agents |
| SCY-635 |
Cyclophilin inhibitor |
Scynexis |
II |
| Miravirsen |
miRNA122 antisense NA |
Santaris |
II |
| RG-101- |
miRNA122 antisense NA |
Regulus |
II |
| TT-0034 |
RNA interference with HCV |
Tacere Therapeutics |
II |
Our Services
To develop effective therapies and a vaccine for Hepatitis C, several processes have to be accomplished in parallel. These include a comprehensive understanding of the virus, new and practical scientific techniques, and detailed pre-clinical work. With an intricate understanding of HCV biology and with our addditional strength in tailoring vaccines and drugs, our team is equipped to handle the offering of customized services which hastens the efforts of our clients on effective interventions against hepatitis C.
Preclinical Research
- Pharmacodynamics Study Services
- Pharmacokinetics Study Services
- Drug Safety Evaluation Services
Disease Models
- Murine Models of HCV Entry and Infection
- HCV Infection Chimpanzee Models
- George Baker Virus B (GBV-B) Infection NHP Models
- Equine Hepacivirus (EqHV) Infection NHP Models
- Rodent Hepacivirus (RHV) Infection NHP Models
Our preclinical research services are designed to bridge the gap between discovery and clinical development. These services encompass:
- Viral Challenge Studies: Effect evaluation of candidate vaccines by using severe animal models.
- Immunological Measurements: Estamation of the protective response created by vaccine candidates such as neutralizing antibodies and T-cells.
- Pharmacokinetic and Pharmacodynamic Studies: Defining the absorption, distribution, metabolism and elimination patterns of the tested therapeutic candidates.
If you need information on our services, do not hesitate to reach out to us.
References
- Manns, Michael P., et al. "Hepatitis C virus infection." Nature reviews Disease primers 3.1 (2017): 1-19.
- Morozov, Vladimir Alexei, and Sylvie Lagaye. "Hepatitis C virus: Morphogenesis, infection, and therapy." World journal of hepatology 10.2 (2018): 186.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
