Abstract: The present invention provides novel recombinant protein and peptide inhibitors of NS3 serine protease of the hepatitis C virus (HCV). The invention discloses analogs, fragments and derivatives of the identified inhibitors, nucleic acids encoding same, and methods of use thereof for the treatment of HCV infection. The invention further provides novel constructs and methods for the screening of protease inhibitors in vivo, using a recombinant engineered reporter protein that is cleavable by a protease, co-expressed with the recombinant protease in bacteria.