Recent Highlights in the Synthesis of Anti-HCV Ribonucleosides

Abstract

Research on Hepatitis C Virus inhibitors has dramatically increased during the past few years. Actually, several classes of anti-HCV drugs, including NS3/4A protease inhibitors, NS5B polymerase inhibitors, NS4B protein to RNA binding inhibitors, and multifunctional viral protein NS5A inhibitors, are in different stages of development. The RNA dependent HCV polymerase is considered an irreplaceable target for future HCV therapy on account of a high degree of conservation across the six HCV genotypes, and agents targeting the active site, such as ribonucleoside analogs, may be particularly advantageous having a high barrier to resistance. The purpose of this review is to present highlights of recent developments in the synthesis of anti-HCV ribonucleosides and to discuss the limitations posed by resistance and drug toxicity.

The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

“…The gene encoding the viral RNA polymerase shows the highest degree of conservation among the members of the Flaviviridae family16, and the clinically approved anti-HCV drug sofosbuvir targets this protein. Sofosbuvir is an uridine nucleotide prodrug, which is triphosphorylated within cells to target the viral RNA polymerase17.…”

The clinically approved antiviral drug sofosbuvir impairs brazilian zika virus replication

“…Among the Flaviviridae family, the gene encoding the RNA polymerase shows the highest degree of conservation (15). Therefore, new therapeutic options against HCV, specially targeting the viral RNA polymerase, could have a broader spectrum over other members of the Flaviviridae family.…”

Recent advances on the synthesis of hepatitis C virus NS5B RNA-dependent RNA-polymerase inhibitors

“…Huge numbers of NS5B polymerase inhibitors have been designed and synthesized, which were mainly classified into nucleoside inhibitors (NIs) and not-nucleoside inhibitors (NNIs) [108]. [109], and ABT-333 has entered in phase III trials now. With the significant progress in understanding of molecular virology of HCV, and the advances in the drug development process such as HTS and structure based drug design, the development of different structural NS5B polymerase inhibitors will be greatly accelerated [108].…”