The myth of venom cytotoxin: the way forward

Written by Dr. Yap Khai Khun, Michelle, School of Science

What is your Research About?

My research focuses on venom toxins’ pharmacology and next-generation biotherapeutic. Envenomation by snakes was listed as Category A Neglected Tropical Diseases (NTD) by the World Health Organisation in 2017, indicates a serious public health problem. The global figures for envenomation cases were estimated to be more than 1.8 million annually. Nonetheless, the actual burden could be more than this number. Cobra envenomation appears to be one of the commonest causes of envenomation with high rates of morbidity and mortality. Cobra envenomation is clinically manifested with systemically neuromuscular paralysis, ventilatory failure, and local dermonecrosis. Dermonecrosis causes permanent disability in the affected patients due to amputations, deformities, contracture, or even chronic ulceration. The key venom toxin associated with dermonecrosis is due to substantial levels of cytotoxin in cobra venom (Yap et al., 2014a, b). My research emphasises its pharmacology, molecular targets, and epitope properties.

Why is it important?

The existing immunotherapy, however, is ineffective in the treatment of dermonecrosis because cytotoxin appears to be low immunogenicity, these local effects thus end up in sequelae. There is a global shortage of the targeted biotherapeutics attributed to inadequate knowledge on cytotoxicity and the molecular targets (global antivenom crisis). There is an urgent need for this NTD to be viewed and aligned with WHO commitment to achieve UN SDG.

What are the outcomes/potential outcomes?

The cytotoxicity of cytotoxin is a concentration-dependent process (Teoh and Yap, 2020), whereby there is a transition of apoptosis to necroptosis at increasing toxin levels. It is then used as a candidate toxin for epitope characterisation for new biotherapeutic. Our preliminary findings showed that the toxin epitopes presumably contribute to its functionality in dermonecrosis. Our next move is to characterise the epitope properties as an enriched target for the biotherapeutic. We look forward to establishing a new partnership in the discipline.

Is there Global and Societal Impact?

The long-term research impact addresses the global commitment and supports the SRPNTS program in combating the envenomation as serious NTD problems and aligns with UN SDGs Goal targets: (1) goal 3.3: Combat the undesired pathological outcomes due to dermonecrosis that leading to disability and deformity in the affected patients; (2) goal 3.8: Safe, effective, affordable and new biotherapeutic targeting dermonecrosis to mitigate deformity and disability in the affected patients.