This article first appeared on our sister website, HCPLive.
- Host-targeting agents (HTAs) offer a unique approach to antiviral tactics against HCV.
- RNA interference (RNAi) and microRNA-122-based approaches show potential for suppressing HCV.
- Nanoparticle-based delivery of HCV immunization, testing, and therapeutics is gaining interest.
Hepatitis C virus (HCV) treatment is prominently led by the direct-acting antiviral (DAA) drug class, a staple of viral mitigation in patients for the last decade now. However, advances in treatment diversity and potential prevention are still pursued—despite DAAs’ significant efficacy.
A recent review from Adane Adugna, of the College of Health Sciences at Debre Markos University in Ethiopa, addressed a number of these drug classes and therapeutic practices beyond DAAs in an investigation and particular practice for the treatment of HCV.
Host-targeting agents (HTAs)
HTAs provide a “fascinating viewpoint for antiviral tactics toward HCV,” Adugna wrote, as the host protein sequence-targeting agents provide a significant genetic hurdle, as well as antiviral action and strategic action of care supplementary to DAAs that implicate a potential cooperative effect with DAAs in treating HCV.
“Due to the exceedingly low mutational frequency that takes place inside host cells, HTAs offer a wide antiviral action with an extremely high genomic roadblock to drug tolerance,” Adugna wrote.
Investigators have observed potential suppression against HCV with RNA interference (RNAi)-based gene silencing and antisense oligonucleotide-based microRNA-122. Adugna explained that RNAi technology has been contributory to the understanding of HCV entrance and replication, despite concern of safety outcome risks with some agents.
“Theoretically,a range of gene therapy‐based HCV defense mechanisms could be developed based on knowledge of the viral gene sequences,” Adugna wrote. “This intriguing strategy relies on the use of short RNA technology to stop viral enzyme activity and replication.”
Nanoparticle-based delivery of HCV immunization, testing and therapeutic agents have piqued interest from investigators, as the unique qualities of nanomedicine provide resolution to the hurdles of secure treatment delivery in affected patients.
“Anti‐HCV medications were able to have an ongoing impact through pegylating nanoparticles to limit drug absorption from the NPs framework or by magnetically reacting with carriersthathadopposingelectricalcharges,” Adugna wrote. “Additionally, nanotechnology makes it simple to increase serum stability and safeguard anti‐HCV drugs.”
Anti-programmed cell death 1 (PD-1)
“In patients with chronic hepatitis C, PD‐1 can be seen on the cell surface of CD8+ T lymphocytes that are specific for the HCV infection,” Adugna explained. “On CD8+ T cells that are specifically targeting intact class I HCV epitopes without escape mutations to evade immune identification; this inhibitory receptor is expressed at its highest level.”
Patients with chronic HCV face compromised immune response due to increased PD-1, PD-L1 or CTLA-4. By administering immunotherapy designed to block such levels by reactivating immune response to the viral antigen, investigators may be able to provide targeted benefit for hepatitis C.
Monoclonal antibodies and monocyte-derived dendritic cells (Mo-DCs)
A common drug class in inflammatory and immune-mediated disease, monoclonal antibodies could target viral and host receptors, such as anti-scavenger receptor class B type I. This mechanism of action could inhibit some of the cellular components that are essential to the HCV lifecycle.
Mo-DCs loaded with virus-specific lipopeptide may also be possibly used to treated HCV.
“To treat the patients, 6 lipopeptides made up of human leukocyte antigen‐A2 (HLA‐A2)‐restricted HCV‐specific cytotoxic T lymphocyte (CTL) epitopes were pulsed into the Mo‐DCs,” Adugna wrote. “Each of these lipopeptides was connected toa common Th epitope and the TLR2 agonist.”
Promising vaccine candidate
Adugna lastly highlighted progress in the development of a potential HCV prophylaxis—a prospect that which has evaded investigators due to the significant genetic variability of HCV, including 100 subgroups and 8 different genotypes.
“Furthermore, lackof an effective tissue culture method for replicating HCV, inadequate knowledge of immune responses that are protective against HCV, lack of evaluating neutralizing antibodies, and the ability of HCV to create multiple approaches to inhibit natural immune signaling and mask antigenic determinants were the previous challenges for the advancement of HCV vaccine with high protective efficacy,” Adugna explained.
All the same, prospective mRNA vaccines, borne out of massive progress and development during the COVID-19 pandemic, are coming to the forefront of early-stage investigation, as well as vaccines targeting a peptide comprised of overlapping components of the p7 protein. Adugna noted that “powerful immunogenic peptides created through chemical synthesis” are emerging as potentially viable HCV vaccine candidates.
“Recombinant proteins, peptides, virus‐like particles(VLP), bare DNA, and recombinant viruses are among the novel vaccination options being investigated,” Adugna wrote. “The feasibility of production, the ease of altering DNA, and immune responses largely coming from many sources, like T helper cells and CTLs, as well as antibody responses, are all benefits of DNA immunization.”
- Adugna A. Therapeutic strategies and promising vaccine for hepatitis C virus infection. Immun Inflamm Dis. 2023;11(8):e977. doi:10.1002/iid3.977
- Walter K. Direct-Acting Antivirals Still Underutilized for HCV Care. HCPLive. Published December 14, 2022. https://www.hcplive.com/view/direct-acting-antivirals-underutilized-hcv-care