In a major research initiative, Novozymes, the global bio-pharmaceutical ingredient major entered into a multi university collaborative effort where it discovered a mechanism by which plectasin, an anti-microbial peptide, kills bacteria that is the cause of severe infections in humans. The research finding has led Novozymes to manufacture the plectasin variant NZ2114 at its cGMP pilot plant in Denmark for the phase I clinical trials to be carried out by sanofi-aventis.

Novozymes identified plectasin in 2002 but it was not until 2005 when Nature magazine published an article about the peptide that it became well-known to the global scientific community. In 2008 Novozymes granted sanofi-aventis an exclusive worldwide license for the development, registration and commercialization of plectasin.

The study was a collaborative effort with scientists at several Universities in Europe including Bonn and Aalborg. The second phase of research was carried out at Novozymes Denmark laboratories in association with the State Serum Institute (SSI), Denmark. The molecule was identified from a fungus living in north of Zealand, Denmark. The activity against ‘staphylococcus incl. MRSA’ of plectasin was improved by protein engineering and screening of more than six lakh plectasin variants were undertaken at the laboratories of Novozymes in Denmark. An improved variant plectasin NZ2114 was isolated and taken to pre-clinical studies, Søren Kjærulff, senior director, Pharma-R&D, Novozymes, Denmark told Pharmabiz in an email interaction.

Peptide antibiotics such as plectasin have retained antibiotic activity through evolution. The new findings indicate that plectasin and other related peptides from invertebrates such as flies and mussels, target the ‘Achilles heel’ of bacteria. It binds and seizes a precursor used in the ‘cell-wall biosynthesis’. Since the bacteria cannot survive without the cell-wall it is instantly killed.

“Plectasin works on bacterial infections that are resistant to conventional antibiotic. An improved derivative out-licensed to sanofi-aventis, NZ2114, even targets severe diseases like pneumonia, endocarditis, meningitis and blood poisoning caused by bacteria like Streptococcus and Staphylococcus which are resistant to all existing antibiotics. This will make it an effective new weapon for doctors, who are currently powerless in the face of these infections,” stated the senior director, Pharma-R&D of Novozymes.

Novozymes which is known for its research and production of a range of industrial enzymes has significant focus on the bio-pharmaceutical space. The company is also working with a peptide against resistant gram negative bacterial infections which are among the other research initiatives planned for this fiscal, he said.