Structure-Based Drug Discovery for Botulinum Neurotoxins
Biology Department, Brookhaven National Laboratory, Upton, NY, 11973, USA, .Current topics in microbiology and immunology (Impact Factor: 4.1). 01/2013; 364:197-218. DOI: 10.1007/978-3-642-33570-9_10
Clostridium botulinum neurotoxin is the most poisonous substance known to humans. It is a potential biowarfare threat and a public health hazard. The only therapeutics available is antibody treatment which will not be effective for post-exposure therapy. There are no drugs available for post-intoxication treatment. Accordingly, it is imperative to develop effective drugs to counter botulism. Available structural information on botulinum neurotoxins both alone and in complex with their substrates offers an efficient method for designing structure-based drugs to treat botulism.
- The Comprehensive Sourcebook of Bacterial Protein Toxins, 01/2006: pages 348-389; , ISBN: 9780120884452
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ABSTRACT: Botulism is a severe neuroparalytic disease resulting from exposure to one of the most poisonous toxins to humans. Because of this high potency and the use of toxins as biological weapons, botulism is a public health concern and each case represents an emergency. Current therapy involves respiratory supportive care and anti-toxins administration. As a preventive measure, vaccination against toxins represents an effective strategy but is undesirable due the rarity of botulism and the effectiveness of toxins in treating several neuromuscular disorders. This paper summarizes the current issues in botulism treatment and prevention, highlighting the challenge for future researches.Expert Review of Anti-infective Therapy 08/2014; 12(9):1-12. DOI:10.1586/14787210.2014.945917 · 2.25 Impact Factor
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ABSTRACT: Botulinum Neurotoxins are the most poisonous of all toxins with lethal dose in nanogram quantities. They are also 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.Current Topics in Medicinal Chemistry 03/2015; 15(7). DOI:10.2174/1568026615666150309150338 · 3.40 Impact Factor
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