Limits...
Finally sofosbuvir: an oral anti-HCV drug with wide performance capability.

Kayali Z, Schmidt WN - Pharmgenomics Pers Med (2014)

Bottom Line: Initially, interferon and ribavirin therapy was the treatment standard of care, but it offered limited performance across the wide spectrum of HCV disease and was fraught with excessive and often limiting side effects.SOF is safe and can be used across different viral genotypes, disease stages, and special patient groups, such as those coinfected with human immunodeficiency virus.More so than any other anti-HCV drug developed to date, SOF offers the widest applicability for all infected patients, and new regimens will be tailored to maximize performance.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, University of Southern California, Los Angeles, CA, USA.

ABSTRACT
Chronic Hepatitis C virus (HCV) infection is the leading cause of advanced liver disease worldwide. The virus successfully evades host immune detection and for many years has hampered efforts to find a safe, uncomplicated, and reliable oral antiviral therapy. Initially, interferon and ribavirin therapy was the treatment standard of care, but it offered limited performance across the wide spectrum of HCV disease and was fraught with excessive and often limiting side effects. Sofosbuvir (SOF) is a potent first-in-class nucleoside inhibitor that has recently been approved for treatment of HCV. The drug has low toxicity, a high resistance barrier, and minimal drug interactions with other HCV direct-acting antiviral agents such as protease inhibitors or anti-NS5A agents. SOF is safe and can be used across different viral genotypes, disease stages, and special patient groups, such as those coinfected with human immunodeficiency virus. When used in combination with ribavirin or another direct-acting antiviral agent, SOF has revolutionized the HCV treatment spectrum and set the stage for nearly universal HCV antiviral therapy. More so than any other anti-HCV drug developed to date, SOF offers the widest applicability for all infected patients, and new regimens will be tailored to maximize performance.

No MeSH data available.


Related in: MedlinePlus

Activation of sofosbuvir.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4270038&req=5

f2-pgpm-7-387: Activation of sofosbuvir.

Mentions: Structurally, SOF is a uridine nucleotide prodrug (Figure 2) with rapid intestinal absorption and is easily taken up by hepatocytes from the circulation. Intracellularly, the side chains on the phosphate are removed and the 2′-deoxy-2′-fluoro-2′-C-methyluridine monophosphate GS-606965 is converted into the uridine triphosphate form GS-461203 (Figure 2), which is now able to compete with endogenous uridine triphosphate for incorporation into the growing viral RNA chain (Figure 2).47 After binding of the nucleotide to the RNA chain, further addition of nucleotides is not possible and chain elongation is terminated. Fortunately, the uridine triphosphate form has limited, if any, binding affinity for host RNA or deoxyribonucleic acid polymerases.48


Finally sofosbuvir: an oral anti-HCV drug with wide performance capability.

Kayali Z, Schmidt WN - Pharmgenomics Pers Med (2014)

Activation of sofosbuvir.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4270038&req=5

f2-pgpm-7-387: Activation of sofosbuvir.
Mentions: Structurally, SOF is a uridine nucleotide prodrug (Figure 2) with rapid intestinal absorption and is easily taken up by hepatocytes from the circulation. Intracellularly, the side chains on the phosphate are removed and the 2′-deoxy-2′-fluoro-2′-C-methyluridine monophosphate GS-606965 is converted into the uridine triphosphate form GS-461203 (Figure 2), which is now able to compete with endogenous uridine triphosphate for incorporation into the growing viral RNA chain (Figure 2).47 After binding of the nucleotide to the RNA chain, further addition of nucleotides is not possible and chain elongation is terminated. Fortunately, the uridine triphosphate form has limited, if any, binding affinity for host RNA or deoxyribonucleic acid polymerases.48

Bottom Line: Initially, interferon and ribavirin therapy was the treatment standard of care, but it offered limited performance across the wide spectrum of HCV disease and was fraught with excessive and often limiting side effects.SOF is safe and can be used across different viral genotypes, disease stages, and special patient groups, such as those coinfected with human immunodeficiency virus.More so than any other anti-HCV drug developed to date, SOF offers the widest applicability for all infected patients, and new regimens will be tailored to maximize performance.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, University of Southern California, Los Angeles, CA, USA.

ABSTRACT
Chronic Hepatitis C virus (HCV) infection is the leading cause of advanced liver disease worldwide. The virus successfully evades host immune detection and for many years has hampered efforts to find a safe, uncomplicated, and reliable oral antiviral therapy. Initially, interferon and ribavirin therapy was the treatment standard of care, but it offered limited performance across the wide spectrum of HCV disease and was fraught with excessive and often limiting side effects. Sofosbuvir (SOF) is a potent first-in-class nucleoside inhibitor that has recently been approved for treatment of HCV. The drug has low toxicity, a high resistance barrier, and minimal drug interactions with other HCV direct-acting antiviral agents such as protease inhibitors or anti-NS5A agents. SOF is safe and can be used across different viral genotypes, disease stages, and special patient groups, such as those coinfected with human immunodeficiency virus. When used in combination with ribavirin or another direct-acting antiviral agent, SOF has revolutionized the HCV treatment spectrum and set the stage for nearly universal HCV antiviral therapy. More so than any other anti-HCV drug developed to date, SOF offers the widest applicability for all infected patients, and new regimens will be tailored to maximize performance.

No MeSH data available.


Related in: MedlinePlus