Application Insight: Sofosbuvir

Sofosbuvir is an anti-hepatitis C active pharmaceutical ingredient. Hepatitis C is a pandemic disease caused by the hepatitis C virus. It is estimated that 71 million people have chronic hepatitis C virus infection which is a major cause of liver cancer and can lead to cirrhosis and its further complications. As there is currently no vaccine for hepatitis C, there is a lot of interest in developing new APIs for the treatment of this disease.

Sofosbuvir inhibits the hepatitis C virus NS3 protease which block hepatitis C virus (HCV) replication. It has proven to be an ideal antiviral agent in difficult-to-treat patients when given with direct acting antiviral agents (DAAs). Its excellent pharmacokinetic profile allows it to be administered as just one tablet daily. It is a large molecule with a synthesis that requires many chemical steps. An immobilized enzyme is typically used as one step in this process for enantioselective hydrolysis of an acetate ester into chiral alcohol.

The use of immobilized enzymes in the pharmaceutical industry is becoming more common-place as they begin to replace traditional chemical processes. The benefits include the possibility to use equimolar concentration of substrates, obtain an enantiomeric excess > 99% and use a column configuration that allows dramatic increases in productivity.

CalB Immo Plus™, a product in our Lifetech™ range, is an immobilized, recombinant Lipase B from Candida antarctica (CalB), produced by microbial fermentation with Pichia pastoris.

It is suitable for solvent-free or organic solvent systems and can be used for regio- and stereoselection esterifications and transesterifications. The lipase itself is immobilized by adsorption onto a highly hydrophobic carrier polymer, in this case Lifetech™ ECR1030M. ECR1030M combined with immobilized CalB makes CalB Immo Plus™ an ideal choice for applications in water, such as that used in the production of Sofosbuvir.

This information has been taken from 'Industrial Applications of Immobilized Enzymes - A Review' by Dr. Alessandra Basso and Dr. Simona Serban.

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(Click to enlarge)

The top figure shows enantioselective hydrolysis of hepatitis C virus inhibitor Sofosbuvir by immobilized CalB in organic solvent saturated with aqueous buffer.

The bottom figure shows the chemical structure of the Sofosbuvir molecule, inhibitor of the hepatitis C virus NS3 protease.