The Role of Interferon for the Treatment of Chronic Hepatitis C Virus Infection

Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

“…From the approval by the FDA in 1991 until 2014, the interferon-based therapy remained the standard treatment for chronic hepatitis. With the advent of direct-acting antiviral (DAA) drugs, the combination of pegylated-interferon-α (PEG-IFN-α) and ribavirin was gradually replaced until the end of 2017 [ 38 ]. Since 2018, the World Health Organization (WHO) has recommended the treatment of adults with chronic HCV infection with a pan-genotypic DAA combination therapy [ 39 ].…”

“…Since 2018, the World Health Organization (WHO) has recommended the treatment of adults with chronic HCV infection with a pan-genotypic DAA combination therapy [ 39 ]. In addition to the short-term treatment, the DAA therapeutic schemes reduced the severe side effects associated with interferon-based therapy, consequently increasing the patient adherence and the treatment effectiveness [ 38 ].…”

The 2020 Nobel Prize in Physiology or Medicine

“…The studies conducted between 1990 and 2000 provided the foundation for the remarkable advances in treating HCV that would occur between 2000 and 2015. In 2002, pegylated IFN-α (PEG IFN-α) was introduced into clinical practice, with the once weekly dosing regimen of the biologic used in conjunction with 1 improving compliance and enhancing SVR to 43–46% (Figure ); however, many of the challenges with the tolerability of this regimen remained, as did the need for 48 weeks of therapy. , Meanwhile, the pharmaceutical industry significantly expanded efforts to discover and develop drug candidates as the tractability of viral targets began to resolve. , Moreover, the need for drug combinations was also anticipated based on prior experience with HIV-1 inhibitors, resulting in parallel discovery programs both within a company and across the industry . This approach would prove to be prescient since all currently marketed therapies are a combination of two or three drugs that act by orthogonal mechanisms, a strategy designed to prevent the emergence of resistant virus.…”

“…In 2002, pegylated IFNα (PEG IFN-α) was introduced into clinical practice, with the once weekly dosing regimen of the biologic used in conjunction with 1 improving compliance and enhancing SVR to 43−46% (Figure 1); however, many of the challenges with the tolerability of this regimen remained, as did the need for 48 weeks of therapy. 11,19 Meanwhile, the pharmaceutical industry significantly expanded efforts to discover and develop drug candidates as the tractability of viral targets began to resolve. 20,21 Moreover, the need for drug combinations was also anticipated based on prior experience with HIV-1 inhibitors, resulting in parallel discovery programs both within a company and across the industry.…”

“…46 Mavyret combines the more powerful NS5A inhibitor pibrentasvir (18) with the pangenotype NS3/4A inhibitor glecaprevir (10) and was approved to treat GT 1−6 infection in the U.S. in 2017. 47 Zepatier is a fixed-dose combination of elbasvir (19) and grazoprevir (9) approved in the U.S. in 2016 as therapy for GT 1 and 4 infections. 48 In addition to the challenges in drug design presented by HCV targets, the marketed inhibitors have expanded the accepted values for physical property indices of drugs, advancing common parameters well beyond the limits of what was considered to be appropriate, with high molecular weight (MW), cLogP, and polar surface area (PSA) values.…”