Hepatitis C virus (HCV) pharmacotherapy management is dominated by the direct-acting antiviral (DAA) drug class, which has been the mainstay of relieving viral infections in patients over the past decade. However, despite the significant efficacy of DAAs, advances in therapeutic diversity and potential prevention are still sought.
A recent review by Adane Adugna of the Faculty of Health Sciences, Debre Marcos University, Ethiopia, addresses some of the questions
The following are some drug classes and treatment practices outside of DAAs that are under investigation and specific practices for HCV treatment.
Host targeting agents (HTAs)
Adugna writes that HTAs provide a fascinating perspective on HCV antiviral strategies because host protein sequence-targeting agents provide significant genetic barriers, as well as complement the antiviral effects of DAAs and strategic nursing actions, which means that with DAAs treat HCV.
“HTAs have broad antiviral effects and extremely high genomic barriers to drug resistance due to the extremely low frequency of mutations that occur within the host cell,” Adugna wrote.
microRNA
Researchers observed potential inhibitory effects on HCV by RNA interference (RNAi)-based gene silencing and antisense oligonucleotide-based microRNA-122. Adugna explained that RNAi technology can help understand HCV entry and replication, although safety outcomes risks for some drugs are concerning.
“Theoretically, a range of gene therapy-based HCV defense mechanisms could be developed based on knowledge of the viral genetic sequence,” Adugna wrote. “This interesting strategy relies on using short RNA technology to block viral enzyme activity and replication.”
nanomedicine
Nanoparticle-based delivery of HCV immunization, detection, and therapeutic drugs has attracted the interest of researchers because the unique qualities of nanomedicine address barriers to safe treatment delivery for affected patients.
“Anti-HCV drugs are capable of producing sustained effects by pegylating nanoparticles to limit drug uptake from the nanoparticle framework or by magnetically reacting with oppositely charged carriers,” Adugna writes. “Additionally, nanotechnology Serum stability can be easily improved and anti-HCV drugs protected.”
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 specific for HCV infection,” Adugna explains. “CD8+ T cells specifically target the complete class I HCV epitope and have no escape mutations to evade immune recognition; this inhibitory receptor has the highest expression levels.”
Chronic HCV patients face an impaired immune response due to increased PD-1, PD-L1, or CTLA-4. By implementing immunotherapies designed to block this level by reactivating immune responses to viral antigens, researchers may be able to provide targeted benefits for hepatitis C.
Monoclonal antibodies and monocyte-derived dendritic cells (Mo-DC)
Monoclonal antibodies are a common class of drugs in inflammatory and immune-mediated diseases that target viral and host receptors, such as type I and class B anti-scavenger receptors. This mechanism of action inhibits some cellular components necessary for the HCV life cycle.
Mo-DC loaded with virus-specific lipopeptides may also be used to treat HCV.
“To treat patients, Mo-DCs were pulsed with six lipopeptides consisting of human leukocyte antigen A2 (HLA-A2)-restricted HCV-specific cytotoxic T lymphocyte (CTL) epitopes,” Adugna wrote. “These lipids Each of the peptides is linked to a common Th epitope and TLR2 agonist.”
Promising vaccine candidates
Adugna concluded by highlighting progress in the development of potential HCV prevention methods – a prospect that has been overlooked by researchers due to the significant genetic variability of HCV, which includes 100 subgroups and 8 different genotypes.
“Additionally, there is a lack of efficient tissue culture methods for replicating HCV, an insufficient understanding of HCV protective immune responses, a lack of assessment of neutralizing antibodies, and the ability of HCV to create multiple methods to suppress natural immune signaling and mask epitopes previously developed with high protection. Efficacy challenges for HCV vaccines,” Adugna explained.
Nonetheless, the tremendous advances and developments made during the COVID-19 pandemic have led to prospective mRNA vaccines and vaccines targeting peptides composed of overlapping components of the p7 protein, which are at the forefront of early-stage research. Arduña noted that “potent immunogenic peptides generated through chemical synthesis” are emerging as potentially viable candidates for a hepatitis C vaccine.
“Recombinant proteins, peptides, virus-like particles (VLPs), naked DNA, and recombinant viruses are all novel vaccine options under investigation,” Adunya wrote. “The feasibility of production, the ease of altering the DNA, and the fact that immune responses come primarily from multiple sources, such as T helper cells and CTLs, as well as antibody responses, are all benefits of DNA immunity.”
refer to
- Adugna A. Therapeutic strategies and promising vaccines for hepatitis C virus infection. Immunoinflammatory diseases. 2023;11(8):e977. doi:10.1002/iid3.977
- Walter K. Direct-acting antiviral drugs remain underutilized in HCV treatment. HCPLive. Published on December 14, 2022. https://www.hcplive.com/view/direct-acting-antivirals-underutilized-hcv-care