The Sound of Evolution
Sofosbuvir
Mechanism of action:
Sofosbuvir is a hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitor (NS5B RNA-dependent RNA polymerase inhibitor). After entering hepatocytes, sofosbuvir is converted through multiple enzymatic steps into its active form, GS-461203, a uridine triphosphate analog. GS-461203 is mistakenly recognized by the viral NS5B polymerase as UTP and is incorporated into the newly synthesized viral RNA, resulting in termination of RNA synthesis and preventing completion of viral genome replication.
Reference(s):
1. Asselah T et al. (2014). Sofosbuvir for the treatment of hepatitis C virus. Expert Opin Pharmacother.
2. Fung A et al. (2014). Efficiency of incorporation and chain termination determines the inhibition potency of 2'-modified nucleotide analogs against hepatitis C virus polymerase. Antimicrob Agents Chemother.
3. Molina JM et al. (2015). Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. Lancet.