King Cobra and snakebite envenomation: on the natural history, human-snake relationship and medical importance of Ophiophagus hannah

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.

The Target Selects the Toxin: Specific Amino Acids in Snake-Prey Nicotinic Acetylcholine Receptors That Are Selectively Bound by King Cobra Venoms

“…This supports the idea of the geographical variation of venom composition and venom toxicity. Recent quantitative proteomic studies on Malaysian and Javanese King Cobra venoms showed that the crude King Cobra venom of the Javanese locale contains a comparatively higher amount of alpha-neurotoxic 3FTxs, which accounts for 64.2% of total venom proteins with ≥20 subtypes [32]. Conversely, the Malaysian King Cobra venom showed a lower percentage of 3FTxs, which makes up 43% of their total venom proteins with 13 subtypes [32].…”

“…Recent quantitative proteomic studies on Malaysian and Javanese King Cobra venoms showed that the crude King Cobra venom of the Javanese locale contains a comparatively higher amount of alpha-neurotoxic 3FTxs, which accounts for 64.2% of total venom proteins with ≥20 subtypes [32]. Conversely, the Malaysian King Cobra venom showed a lower percentage of 3FTxs, which makes up 43% of their total venom proteins with 13 subtypes [32]. The results obtained from our present study, thus, further reveal a piece of evidence for the compositional variation of King Cobra venom linked with geographical distribution.…”

“…Since Ophiophagus hannah (King Cobra) venom has been shown to be highly selective for snake (Coelognathus radiata) alpha-1 [11], we hypothesized that the prey-specific toxicity of O. hannah is highly correlated with specific amino acids within the snake-prey alpha-1 orthosteric site [32]. To investigate this hypothesis, we used a well-validated novel biolayer interferometry assay [33,34] to screen the venoms of four different types of King Cobras (Cambodian, Javan, Malaysian, and Thai) using native and mutant orthosteric sites.…”

Digital Potency Measurement: A New Approach Methodology for Antisera Effective Dose Assessments

“…It is known that the venom from the cobra snake that belongs to Elapidae family induces neurotoxic (through nicotine acetyl choline receptors) and cytotoxic activity 36,37 The NAM being discussed here with ML tool has trained the software with neuro and cytotoxic phenotype patterns acquired from treated in vitro platform as part of the training the model exercise. The embedded AI picks signals with confidence against the control patterns to detect toxicity-induced cellular phenotypes (Supplementary Figure 1&2) in the assay system while the derived IC50 and potency values reflect the measurable score.…”

Equatorial Spitting Cobra (Naja sumatrana) from Malaysia (Negeri Sembilan and Penang), Southern Thailand, and Sumatra: Comparative Venom Proteomics, Immunoreactivity and Cross-Neutralization by Antivenom

“…For instance, in Southeast Asia, marked geographical venom variation has been reported for the Monocled Cobra (Naja kaouthia) from Malaysia, Thailand and Vietnam, showing variable venom proteomes that correlate with venom toxicity and discrepancy in the neutralization efficacy of antivenom [13,14]. Similarly, intra-specific variations in snake venom composition, antigenicity and neutralization have been reported for various other medically important snakes in Southeast Asia, including Russell's Viper, Malayan Pit Viper, Malayan Krait, Banded Krait and King Cobra [15][16][17][18][19][20]. The variations have ramifications on antivenom use, as antivenoms are usually domestic products manufactured in one locale and thus may have limited efficacy in neutralizing the venom of the same snake species from another geographical area.…”