New Hepatitis C Treatment Found; Pronucleotide-Based Drugs Under Clinical Trial

Nucleoside analogs have been proposed as efficient therapeutic agents for the treatment of viral diseases and cancer. Though their therapeutic potential has been realized for many years, their clinical applicability remains questionable. This can be attributed to the challenges associated with combining it with suitable carrier molecules.

The therapeutic manifestation of a nucleoside analog is subject to the presence of carrier molecules that can escort it inside the cell (via the lipoproteinous membrane) and help in the process of its cellular activation. Hence, scientists started working on the development of biomolecules that can perform the same task even in the absence of carrier molecules. Scientists propose that the new pronucleotide (ProTide) molecules may be the answer to this dilemma.

According to a recent publication in Science, these pronucleotides can cross the bio-membrane without any carrier molecule and can perform the same function as that of nucleoside analogs. Furthermore, they are also immune against degradation by host cell enzymes. This makes them a potential candidate for the production and application of molecular drugs for clinical applications.

However, the widespread application of these molecules is subject to development of suitable methods for their large-scale production. It seems scientists from Merck & Co., Inc. have managed to do just that. They have developed a new molecular catalyst that can fasten the process of large-scale production of therapeutic proucleotides. To do so, researchers implemented the dihydropyrroloimidazole framework along with other analytical methods viz. computational modeling, informatics and kinetic analyses, Phys.org reported.

The catalyst developed by them could help in the formation of chiral phosphorus centers, an essential step for the development of pronucleotides. Further investigations in this regard revealed that combining the catalyst with a chlorophosphoramidate and a nucleoside mediates the development of pronucleotide drugs with the desired chiral properties.

They implemented the combination of the methods and molecules described above to develop a new pharmaceutical formulation, namely, MK-3682. After detailed analysis of the drug at experimental level, the scientists proposed that MK-3682 can be considered as a new hepatitis C treatment method that can easily be scaled up. Scientists have proposed that the same method can be used for the development of novel drugs for the treatment of other chronic diseases including cancer.