Sofosbuvir, a novel nucleotide analogue inhibitor used for the treatment of hepatitis C virus

Abstract

Objective To provide an overview of a novel anti-hepatitis C agent, sofosbuvir. Key findings Sofosbuvir is a novel nucleotide analogue inhibitor of hepatitis C virus (HCV) NS5B polymerase that has recently been approved by the Federal Drug Administration for the treatment of HCV genotypes 1, 2, 3 or 4 in a variety of patients. The emergence of such a novel treatment provides benefit to previously untreated genotypes and patient populations, with little chance of promoting significant viral resistance. Excellent sustained virologic response rates 12 weeks after the end of treatment (SVR12) were seen in phase II and III clinical trials when sofosbuvir was used with ribavirin. Even more promising are the results from phase II and III clinical trials that evaluated sofosbuvir in combination with other oral direct acting antivirals (DAAs). Data with sofosbuvir in the hepatitis C virus (HCV)/HIV coinfected and in the pre-and posttransplantation populations are still emerging. The drug was very well tolerated in clinical studies, with the most common adverse events of headache, nausea and fatigue. Summary Overall, sofosbuvir presents a new and effective treatment option for HCV-infected patients.

A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro

“…The latter group includes compounds that target viral polymerase functions and represent a promising avenue for antiviral exploration. Such compounds are already used to treat other viral infections, including those by human immunodeficiency virus type 1 (HIV-1) (12,13) and hepatitis B and C viruses (14,15). Influenza A viruses have three polymerase proteins: basic polymerase 1 (PB1) is an RNA-dependent RNA polymerase (RdRp); basic polymerase 2 (PB2) binds host-cell capped mRNAs; and the acid polymerase (PA) possesses endonuclease activity that results in removal of the mRNA caps (16).…”

Sofosbuvir: The Discovery of a Curative Therapy for the Treatment of Hepatitis C Virus

“…In a small cohort of GT 5 and 6 patients, the SVR12 was reported as 100%. Subsequent studies demonstrated that even in difficult-to-treat patient populations such as AfricanAmericans, HIV coinfected and liver transplant patients, sofosbuvir regimens demonstrated high cure rates [17,52,56].…”

“…These combination regimens have produced cure rates between 95% and 99% with only 8-12 weeks of therapy. Sofosbuvir has been proven effective in many patient populations that include cirrhotics, patients with advanced liver disease, liver transplant patients and patients who have not responded to other therapies [17].…”

A neighboring group participation strategy: facile synthesis of 3,5-di-O-benzoyl-2-C-methyl-d-arabino-γ-lactone

“…3,5-Di-O-benzoyl-2-deoxy-2-fluoro-2-C-methyl-D-ribono-clactone 1 is an important intermediate for the preparation of sofosbuvir 2, a highly effective drug recently approved for treating chronic hepatitis C. 1 Some other nucleoside HCV NS5B polymerase inhibitors currently under preclinical or clinical studies are also synthesized through this intermediate. [2][3][4][5][6] By now, there have been several routes reported for preparing 1 (Fig.…”