Title:Recent Developments with Metalloprotease Inhibitor Class of Drug Candidates for Botulinum Neurotoxins
Volume: 15
Issue: 7
Author(s): Gyanendra Kumar and Subramanyam Swaminathan
Affiliation:
Keywords:
Bioterrorism, Clostridium botulinum, Drug discovery, Neurotoxin, Protease inhibitor.
Abstract: Botulinum Neurotoxins are the most poisonous of all toxins with lethal dose
in nanogram quantities. They are potential biological warfare and bioterrorism agents
due to their high toxicity and ease of preparation. On the other hand BoNTs are also
being increasingly used for therapeutic and cosmetic purposes, and with that the
chances of accidental overdose are increasing. And despite the potential damage they
could cause to human health, there are no post-intoxication drugs available so far. But
progress is being made in this direction. The crystal structures in native form and bound with substrate peptides have been
determined, and these are enabling structure-based drug discovery possible. High throughput assays have also been designed
to speed up the screening progress. Substrate-based and small molecule inhibitors have been identified. But turning
high affinity inhibitors into clinically viable drug candidates has remained a challenge. We discuss here the latest developments
and the future challenges in drug discovery for Botulinum neurotoxins.
