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Potential para-specific and geographical utility of Thai Green Pit Viper (Trimeresurus albolabris) Monovalent Antivenom: Neutralization of procoagulant and hemorrhagic activities of diverse Trimeresurus pit viper venoms

Yong MY, Tan KY, Tan CH

Toxicon, 2021 Nov;203:85-92.
PMID: 34600909 DOI: 10.1016/j.toxicon.2021.09.021

The Trimeresurus complex consists of diverse medically important venomous pit vipers that cause snakebite envenomation. Antivenoms, however, are in limited supply, and are specific to only two out of the many species across Asia. This study thus investigated the immunoreactivities of regional pit viper antivenoms toward selected Trimeresurus pit viper venoms, and examined the neutralization of their hemotoxic activities. Trimeresurus albolabris Monovalent Antivenom (TaMAV, Thailand) exhibited a higher immunoreactivity than Hemato Bivalent Antivenom (HBAV, raised against Trimeresurus stejnegeri and Protobothrops mucrosquamatus, Taiwan) and Gloydius brevicaudus Monovalent Antivenom (GbMAV, China), attributed to its monovalent nature and conserved antigens in the Trimeresurus pit viper venoms. The venoms showed moderate-to-strong in vitro procoagulant and in vivo hemorrhagic effects consistent with hemotoxic envenomation, except for the Sri Lankan Trimeresurus trigonocephalus venom which lacked hemorrhagic activity. TaMAV was able to differentially neutralize both in vitro and in vivo hemotoxic effects of the venoms, with the lowest efficacy shown against the procoagulant effect of T. trigonocephalus venom. The findings suggest that TaMAV is a potentially useful treatment for envenomation caused by hetero-specific Trimeresurus pit vipers, in particular those in Southeast Asia and East Asia. Clinical study is warranted to establish its spectrum of para-specific effectiveness, and dosages need be tailored to the different species in respective regions.
A genus-wide study on venom proteome variation and phospholipase A2 inhibition in Asian lance-headed pit vipers (genus: Trimeresurus)

Yong MY, Tan KY, Tan CH

Comp Biochem Physiol C Toxicol Pharmacol, 2024 Nov 21.
PMID: 39579840 DOI: 10.1016/j.cbpc.2024.110077

High molecular weight proteins are present abundantly in viper venoms. The amino acid sequence can be highly variable though, contributing to the structure and function diversity of snake venom protein. This, however, remains unresolved in many species. The study investigated the venom protein variability in a distinct clade of Asian pit vipers (Trimeresurus species) through comparative proteomics, applying gel electrophoresis (SDS-PAGE), liquid chromatography-tandem mass spectrometry (LCMS/MS), and bioinformatic approaches. The proteomes revealed a number of conserved protein families, within each are variably expressed protein paralogs that are unrelated to the snake phylogeny and geographic origin. The expression levels of two major enzymes, i.e., snake venom serine proteinase and metalloproteinase, correlate weakly with procoagulant and hemorrhagic activities, implying co-expression of other functionally versatile toxins in the venom. The phospholipase A2 (PLA2) abundance correlates strongly with its enzymatic activity, and a unique phenotype was discovered in two species expressing extremely little PLA2. The commercial mono-specific antivenom effectively neutralized the venoms' procoagulant and hemorrhagic effects but failed to inhibit the PLA2 activities. Instead, the PLA2 activities of all venoms were effectively inhibited by the small molecule inhibitor varespladib, suggesting its potential to be repurposed as a highly potent adjuvant therapeutic in snakebite envenoming.
Seroprevalence of Nipah Virus Infection in Peninsular Malaysia

Yong MY, Lee SC, Ngui R, Lim YA, Phipps ME, Chang LY

J Infect Dis, 2020 05 11;221(Suppl 4):S370-S374.
PMID: 32392323 DOI: 10.1093/infdis/jiaa085

Nipah virus (NiV) outbreak occurred in Malaysia in 1998. The natural host reservoir for NiV is Pteropus bats, which are commonly found throughout Malaysia. Humans become infected when NiV spills over from the reservoir species. In this study, NiV serosurveillance in Peninsular Malaysia, particularly among the indigenous population, was performed. The collected samples were tested for presence of NiV antibodies using a comparative indirect enzyme-linked immunosorbent assay based on the recombinant NiV nucleocapsid (rNiV-N) protein. We found that 10.73% of the participants recruited in this study had antibodies against rNiV-N, suggesting possible exposure to NiV.
Experience of using expired lyophilized snake antivenom during a medical emergency situation in Lao People's Democratic Republic--A possible untapped resource to tackle antivenom shortage in Southeast Asia

Blessmann J, Hanlodsomphou S, Santisouk B, Krumkamp R, Kreuels B, Ismail AK, et al.

Trop Med Int Health, 2023 Jan;28(1):64-70.
PMID: 36416013 DOI: 10.1111/tmi.13833

OBJECTIVES: To evaluate the safety and efficacy of expired lyophilized snake antivenom of Thai origin during a medical emergency in 2020/2021 in Lao People's Democratic Republic.
METHODS: Observational case series of patients with potentially life-threatening envenoming who consented to the administration of expired antivenom between August 2020 and May 2022.
RESULTS: A total of 31 patients received the expired antivenom. Malayan pit vipers (Calloselasma rhodostoma) were responsible for 26 (84%) cases and green pit vipers (Trimeresurus species) for two cases (6%). In three patients (10%) the responsible snake could not be identified. Of these, two presented with signs of neurotoxicity and one with coagulopathy. A total of 124 vials of expired antivenom were administered. Fifty-nine vials had expired 2-18 months earlier, 56 vials 19-36 months and nine vials 37-60 months before. Adverse effects of variable severity were observed in seven (23%) patients. All 31 patients fully recovered from systemic envenoming.
CONCLUSIONS: Under closely controlled conditions and monitoring the use of expired snake antivenom proved to be effective and safe. Discarding this precious medication is an unnecessary waste, and it could be a valuable resource in ameliorating the current shortage of antivenom. Emergency use authorization granted by health authorities and preclinical testing of expired antivenoms could provide the support and legal basis for such an approach.