Journal of Current Toxicology and Venomics - Current Issue

Botulinum neurotoxins are the most poisonous substances reported and listed in category ‘A’ of biowarfare agents. As serotype identification is a time-consuming process and there is no antidote commercially available, the development of inhibitors against serotypes causing human botulism would be beneficial. In the present study, a ligand-based in silico method was applied to identify the “hits” that could have the potential to act as countermeasures against human-intoxicating BoNTs.

For this purpose, a computational approach using Molegro Virtual Docker and AutoDock tools was performed, where around thirty-five derivatives were designed and docked into the catalytic domain of BoNT/A, B, E, and F. The designed compounds were also studied for their ADME properties using an online web tool.

Analysis of the molecular docking data of the complex by Molegro Virtual Docker revealed a high binding affinity between the target and designed ligands, with the MolDock score between -139.85 and -88.24 kcal/mol, whereas the AutoDock score ranged between -11.65 and -5.30 kcal/mol. Three SMNPIs, A11, A18, and A20, exhibited better binding affinities with the target proteins BoNT/A, /B, E, and /F and could be potential pan-active inhibitors. The ADME/T study showed that the designed ligands were less toxic and possessed drug-resemblance properties by considering the Lipinski, Ghose, Veber, and Egan rules, with a bioavailability score of 0.56.

Our study provides insight into ‘hits’, which can lead to further progress in experimental studies and the development of new antidotes for botulism.

Stonefish envenoming occurs when a person comes in contact with the fish’s dorsal spines. This results in immediate and severe pain, with some reports of necrosis and limb swelling, and rare reports of death. While management focuses on pain management, an antivenom is available with a number of reports of improving pain. However, the evidence of the effectiveness of antivenom is based on case reports and animal work. A recent case series from Australia reported five cases where stonefish antivenom did not relieve pain and further analgesia was required. There are differing opinions in Australia on whether stonefish antivenom should be used in the management of stonefish envenoming.

Two patients, aged 40 and 50 years, were stung on a finger when putting their hands into water in northern Australia. Both of them felt immediate and severe pain, and developed cyanosed fingers. Both of the patients received 20 mg intravenous morphine and hot water first aid, but remained in severe pain. Both of them also received 1 ampoule (2000 U) of Sequirus stonefish antivenom, and within 1 hour of the antivenom commencement, the pain was gone, and digit discolouration had markedly improved. There was no adverse reaction of the antivenom observed, and both the patients were pain-free with normal fingers at follow-up weeks later.

We have, herein, reported two cases of presumed stonefish sting where early administration of intravenous stonefish antivenom has appeared to resolve the severe pain and resulted in a marked improvement in digit discolouration. Further work is required to better understand the stonefish venom and how effective stonefish antivenom is in the treatment of stonefish envenoming.