Botulinum Toxin as a Biological Warfare Agent: Poisoning, Diagnosis and Countermeasures

Botulinum toxin is a neurotoxin produced by Clostridium botulinum and some other relative species. It causes a lethal disease called botulism. It can enter the body via infections by Clostridium (e.g. wound and children botulism) or by direct contact with the toxin or eating contaminated food (food-borne botulism). Botulinum toxin is also considered as a relevant biological warfare agent with an expected high number of causalities when misused for bioterrorist or military purposes. The current paper surveys the actual knowledge about botulinum toxin pathogenesis, the manifestation of poisoning, and current trends in diagnostics and therapeutics. Relevant and recent literature is summarized in this paper.

Microwave-assisted Synthesis and Docking Studies of Phenylureas as Candidates for the Drug Design Against the Biological Warfare Agent Yersinia Pestis

Background: Bubonic plague is amongst the diseases with the highest potential for being used in biological warfare attacks today. This disease, caused by the bacterium Yersina pestis, is highly infectious and can achieve 100% of fatal victims when in its most dangerous form. Besides, there is no effective vaccine, and the chemotherapy available today against plague is ineffective if not administered at the beginning of the infection. Objective: Willing to contribute for changing this reality we propose here new phenylureas as candidates for the drug design against plague meant to target the enzyme dihydrofolate reductase from Y. pestis (YpDHFR). Methods: Seven phenylureas, four of them new, were synthesized, following synthetic routes adapted from procedures available in the literature, and using microwave irradiation. After, they were submitted to docking studies inside YpDHFR and human DHFR (HssDHFR) in order to check their potential as selective inhibitors. Results: Our results revealed four new phenylureas and a new synthetic route for this kind of molecule using microwave irradiation. Also, our docking studies showed that these compounds are capable of binding to both HssDHFR and YpDHFR, with U1 - U4 and U23 showing more selectivity for HssDHFR and U7, U8 being more selective towards YpDHFR. Conclusion: We reported the synthesis with good yields of seven phenylureas, following a simple and clean alternative synthetic route using microwave irradiation. Further molecular docking studies of our compounds suggested that two are capable of binding more selectivity to YpDHFR, qualifying as potential candidates for the drug design of new drugs against plague.

Glanders: re-emergence of an ancient zoonosis

Glanders, although known to be endemic in certain regions/countries of the Old and New Worlds for centuries, had been largely overlooked as a threat to equine and human health until the disease re-emerged in the Middle East in 2004. The exponential growth in international horse movements, both legal and illegal, mainly for performance purposes, has enhanced the risk of global spread of glanders in the Middle East and elsewhere. Ever since the First World War, the glanders bacillus has been recognised as a potential biological warfare agent.

Plague: Yersinia pestis

Bubonic plague is a flea-borne zoonosis caused by the Gram-negative bacterium Yersinia pestis, which mainly affects small burrowing mammals including domestic rats. Human disease occurs in endemic countries—currently mainly in Africa (including Madagascar)—following bites from fleas recently hosted by a bacteraemic animal. Historical use of Y. pestis as a biological warfare agent has raised fears of its future use in bioterrorism. The commonest presentation is acute painful lymphadenitis (80–95% of suspected cases), with sudden onset of fever, chills, weakness, headache, and development of an intensely painful swollen lymph node (bubo). Primary septicaemia with no bubo occurs in 10% of cases. Spread to the lungs occurs in less than 10% of cases, resulting in pneumonia which can result in onward respiratory transmission by droplet infection. Overall mortality without treatment is 50–90%.