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.

Keywords: Antivenom; Neglected tropical disease; Neutralization; Proteomics; Venomics.

Figure 1.. (A) Natural distribution of King Cobra in Southeast Asia, southern China, north and north-eastern India, and the Western Ghat of India. (B) Adult King Cobra, Malaysia, with pale olive coloration (photo by Chia How Lee, reprinted with permission). (C) Adult King Cobra, likely Western Ghats of India, in glossy black color with cross-bars (photo by Michael Allen Smith from Seattle, USA, CC BY-SA 2.0, via Wikimedia Commons). (D) Adult King Cobra, Odisha State, eastern India, with brownish bronze coloration and crossbars (photo by Mark O'Shea, https://www.markoshea.info/oba3-1_india01.php, reprinted with permission). (E) Juvenile King Cobra (Malaysia) in growth transition, with crossbars which will disappear into adulthood (photo by Chia How Lee, reprinted with permission). (F) Schematic representation of the phylogenetics of King Cobra in relation to extant elapids (tree simplified from Figueroa et al. [19]).

Figure 2.. Feeding behavior of King Cobra. Ophiophagy is observed in (A, B) adult and (C) juvenile King Cobras, feeding on a corn snake, Gerald’s water snake, and bridle snake, respectively (A, photo by viperskin, CC BY-NC-SA 2.0, via Flickr; B, photo by Lip Kee, CC BY-SA 2.0, via Flickr; C, photo by Chia How Lee, reprinted with permission). These were smooth-scaled preys that King Cobras prefer over snakes with keeled scales. (D) Opportunistic feeding on rodents, in captive environments (photo by Chia How Lee, reprinted with permission).

Figure 3.. Relationship between King Cobra and humans. (A) Footage from ‘Wheels across India’ (Armand Denis, Leila Roosevelt; 1940) of a religious ceremony held in Burma (Myanmar) involving a priestess attempting to kiss a King Cobra on its head three times to obtain the favor of the Snake God of Fertility. (B) Snake educational show at the snake farm of Queen Saovabha Memorial Institute, Bangkok (screenshot from a YouTube clip: www.youtube.com/watch?v=fWh-XOKJgxM). (C) Snake show as a touristic attraction: performer at the Ban Khok Sa-nga King Cobra Village (Thailand) attempting to hold the King Cobra’s head in his mouth (photo by Andrea Pistolesi, https://andreapistolesi.wordpress.com/2010/02/23/who-is-the-snake-who-is-the-victim/). (D) Bags of King Cobras in a wildlife trade market, China. (E) King Cobra medicinal liquor (photo by Viethavvh, CC BY-SA 3.0, via Wikimedia Commons). (F) Village cooking of King Cobra, a source of animal protein in rural areas (screenshot from a YouTube clip: www.youtube.com/watch?v=2Ut0KJv16hg). (G) Menu with “snake thick soup” placed against century-old wooden drawers marked with “venomous snake” (where live snakes were kept) in a restaurant, Hong Kong (©zolimacitymag.com, all rights reserved). Such exotic foods are considered a delicacy and traditional health tonic.

Figure 4.. (A-D) Posting on social media showing close contact with the King Cobra. Sources: A-B, “whispering” (from www.facebook.com/wira.penyelamat.3); C, kissing (screenshot from a YouTube clip, www.youtube.com/watch?v=qN5x9raeaMI); D, petting and stroking (screenshot from a YouTube clip, www.youtube.com/watch?v=sX6DS98BhUk). (E) A snake catcher demonstrating the classical pose of “holding up the King Cobra” barehandedly (screenshot from a YouTube clip https://www.youtube.com/watch?v=0ypL-l2laPQ). (F) Snake intrusion alert on a hot day: a King Cobra was spotted slithering into a house in Malaysia (screenshot from a YouTube clip: www.youtube.com/watch?v=F6L_YaWxIA4).

Figure 5.. First aid of snakebite and a simplified algorithm for clinical management of snakebite (with a focus on King Cobra) envenomation. OhMAV: Ophiophagus hannah Monovalent Antivenom; NPAV: Neuro Polyvalent Antivenom; HPAV: Hemato Polyvalent Antivneom.

Figure 6.. Collection of King Cobra venom. (A) Milking of venom by inducing the snake to bite through a film-covered clean container. (B) Freshly milked venom with its bright golden color. (C) Venom powder in different shades of yellow obtained through lyophilization for long-term storage.

Figure 7.. Schematic representation of geographical variation in the lethality of King Cobra venom sourced from different locales: Bangkok (Thailand), Seremban (West Malaysia), Guangzhou (China) and Java Island (Indonesia). The differential potency of King Cobra-specific antivenom, OhMAV and locally used non-specific antivenoms, NaMAV (China) and SABU (Indonesia), in neutralizing the venom lethality was illustrated. OhMAV: Ophiophagus hannah Monovalent Antivenom (produced in Thailand); NaMAV: Naja atra Monovalent Antivenom (produced in China); SABU: Serum Anti Bisa Ullar (produced in Indonesia).