Hepatitis C virus nonstructural protein 5A

Nonstructural protein 5A (NS5A) is a

• FDA-approved:
  • Ledipasvir, approved on October 10, 2014 in a fixed-dose combination (FDC) with sofosbuvir
  • Ombitasvir, approved on December 19, 2014 in a FDC with paritaprevir and ritonavir, co-packaged with dasabuvir
  • Daclatasvir, approved on July 24, 2015
  • Elbasvir, approved on January 28, 2016 in a FDC with grazoprevir
  • Velpatasvir, approved on June 28, 2016 in a FDC with sofosbuvir and on July 17, 2017 in a FDC with sofosbuvir and voxilaprevir
  • Pibrentasvir, approved on August 3, 2017 in a FDC with glecaprevir
• Investigational drugs:
  • Odalasvir
  • Ravidasvir
  • Ruzasvir
  • Samatasvir

Intragenic complementation

Multiple copies of a polypeptide encoded by a gene often can form an aggregate referred to as a multimer. When a multimer is formed from polypeptides produced by two different mutant alleles of a particular gene, the mixed multimer may exhibit greater functional activity than the unmixed multimers formed by each of the mutants alone. When a mixed multimer displays increased functionality relative to the unmixed multimers, the phenomenon is referred to as intragenic complementation.^{[citation needed]}

NS5A protein is a multimer, a dimer in this case, and intragenic complementation of replication-defective NS5A alleles has been demonstrated by Fridell et al.^[10] On the bases of pairwise complementation tests between different NS5A mutant alleles, they identified three complementation groups that were considered to define three distinct and genetically separable functions of NS5A in RNA replication.

See also

• Discovery and development of NS5A inhibitors

References