Abstract
King Cobra (Ophiophagus hannah) has a significant place in many cultures, and is a medically important venomous snake in the world. Envenomation by this snake is highly lethal, manifested mainly by neurotoxicity and local tissue damage. King Cobra may be part of a larger species complex, and is widely distributed across Southeast Asia, southern China, northern and eastern regions as well as the Western Ghats of India, indicating potential geographical variation in venom composition. There is, however, only one species-specific King Cobra antivenom available worldwide that is produced in Thailand, using venom from the snake of Thai origin. Issues relating to the management of King Cobra envenomation (e.g., variation in the composition and toxicity of the venom, limited availability and efficacy of antivenom), and challenges faced in the research of venom (in particular proteomics), are rarely addressed. This article reviews the natural history and sociocultural importance of King Cobra, cases of snakebite envenomation caused by this species, current practice of management (preclinical and clinical), and major toxinological studies of the venom with a focus on venom proteomics, toxicity and neutralization. Unfortunately, epidemiological data of King Cobra bite is scarce, and venom proteomes reported in various studies revealed marked discrepancies in details. Challenges, such as inconsistency in snake venom sampling, varying methodology of proteomic analysis, lack of mechanistic and antivenomic studies, and controversy surrounding antivenom use in treating King Cobra envenomation are herein discussed. Future directions are proposed, including the effort to establish a standard, comprehensive Pan-Asian proteomic database of King Cobra venom, from which the venom variation can be determined. Research should be undertaken to characterize the toxin antigenicity, and to develop an antivenom with improved efficacy and wider geographical utility. The endeavors are aligned with the WHO´s roadmap that aims to reduce the disease burden of snakebite by 50% before 2030.
Highlights
Snakebite envenomation is a medical emergency characterized by the toxic manifestation of snake venom
The only species-specific antivenom indicated for treating King Cobra envenomation (Ophiophagus hannah Monovalent Antivenom, OhMAV) is produced in Thailand by the Queen Saovabha Memorial Institute, Bangkok, raised against the venom of Thai King Cobra
Clinical reports showed that high doses of the mono-specific King Cobra antivenom, often beyond 20 vials, were needed in the treatment of King Cobra envenomation
Summary
Snakebite envenomation is a medical emergency characterized by the toxic manifestation of snake venom. Intra-species variation in snake venom is widely recognized, adding complexity to the management of snakebite as antivenom products are usually manufactured using snake venom sourced from certain locale without considering the potential in-space (geographical) and in-time (ontogenic) variability of venom composition, as well as composition variation possibly caused by sexual dimorphism of the snake [13,14] This remains true for the case of King Cobra (Ophiophagus hannah), a medically important elapid that has a wide biogeographical distribution in Asia. Climate change (global warming, flash floods) and other anthropogenic factors that result in the clearing of wildlife habitat contribute to the increasing incidence of snake intrusion into human settlement, resulting in human-snake conflicts These will emerge as the leading causes of King Cobra envenomation in the future, considering that awareness practice and protective equipment may reduce the risk of snakebite among the rural and agricultural populations. GELFrEE Solution isoelectric focusing In-solution digestion LC-MS/MS (number of distinct proteoforms in parentheses)
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