Editing King cobra (section)

== Venom ==
[[File:Ophiophagus hannah skull.jpg|thumb|Lateral view of a king cobra skull with fangs]]

===Composition===
[[Venom]] of the king cobra, produced by the postorbital [[venom gland]]s, consists primarily of [[three-finger toxin]]s (3FTx) and [[Metalloproteinase|snake venom metalloproteinases]] (SVMPs).<ref>{{cite journal |author1=Li, J. |author2=Zhang, H. |author3=Liu, J. |author4=Xu, K. |year=2006 |title=Novel genes encoding six kinds of three-finger toxins in ''Ophiophagus hannah'' (king cobra) and function characterization of two recombinant long-chain neurotoxins |journal=Biochemical Journal |volume=398 |issue=2 |pages=233–342 |doi=10.1042/BJ20060004|pmid=16689684 |pmc=1550305}}</ref><ref name="HT">{{cite journal |pmid=20071329 |title=Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of ''Ophiophagus hannah'' (King Cobra) |year=2010 |last1=Roy |first1=A. |last2=Zhou |first2=X. |last3=Chong |first3=M. Z. |last4=d'Hoedt |first4=D. |last5=Foo |first5=C. S. |last6=Rajagopalan |first6=N. |last7=Nirthanan |first7=S. |last8=Bertrand |first8=D. |last9=Sivaraman |first9=J. |volume=285 |issue=11 |pages=8302–8315 |doi=10.1074/jbc.M109.074161 |pmc=2832981 |journal=The Journal of Biological Chemistry |last10=Kini|first10=R. M. |doi-access=free}}</ref>

Of all the 3FTx, [[alpha-neurotoxin]]s are the predominant and most lethal components when [[cytotoxins]] and [[cardiotoxin|beta-cardiotoxin]]s also exhibit toxicological activities.<ref>{{cite journal |author=Chang, L.-S. |author2=Liou, J.-C. |author3=Lin, S.-R. |author4=Huang, H.-B. |pmid=12056805 |year=2002 |title=Purification and characterization of a neurotoxin from the venom of ''Ophiophagus hannah'' (king cobra) |volume=294 |issue=3 |pages=574–578 |doi=10.1016/S0006-291X(02)00518-1 |journal=Biochemical and Biophysical Research Communications}}</ref><ref>{{cite journal |author1=He, Y. Y. |author2=Lee, W. H. |author3=Zhang, Y. |year=2004 |title=Cloning and purification of alpha-neurotoxins from king cobra (''Ophiophagus hannah'') |journal=Toxicon |volume=44 |issue=3 |pages=295–303 |doi=10.1016/j.toxicon.2004.06.003|pmid=15302536 |bibcode=2004Txcn...44..295H}}</ref><ref>{{cite journal |author=Rajagopalan, N. |author2=Pung, Y. F. |author3=Zhu, Y. Z. |author4=Wong, P. T. H. |author5=Kumar, P. P. |author6=Kini, R. M. |title=β-Cardiotoxin: A new three-finger toxin from ''Ophiophagus hannah'' (King Cobra) venom with beta-blocker activity |doi=10.1096/fj.07-8658com |year=2007 |journal=The FASEB Journal |volume=21 |issue=13 |pages=3685–3695 |doi-access=free |pmid=17616557|s2cid=21235585}}</ref> It is reported that [[cytotoxicity]] of its venom varies significantly, depending upon the age and locality of an individual.<ref>{{cite journal |author=Bianca Op den Brouw|author2=Manuel Fernandez-Rojo|author3=Tom Charlton|author4=Bryan G. Fry|author5=Maria P. Ikonomopoulou|pmid=12056805 |year=2023 |title=Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography |volume=15|issue=9 |doi=10.3390/toxins15090549|journal= Toxins|pages=574–578 |doi-access=free |pmc=10534572}}</ref> Clinical [[cardiotoxicity]] is not widely observed, nor is [[nephrotoxicity]] present among patients bitten by this species, presumably due to the low abundance of the toxins.<ref name="Davidson"/>

SVMPs are the second most protein family isolated from the king cobra's venom, accounting from 11.9% to 24.4% of total venom proteins.<ref name=Malaysian/><ref name=Indonesian>{{Cite journal|last1=Petras |first1=D. |last2=Heiss |first2=P. |last3=Süssmuth |first3=R. D. |last4=Calvete |first4=J. J. |date=2015 |title=Venom proteomics of Indonesian King Cobra, ''Ophiophagus hannah'': Integrating top-down and bottom-up approaches |journal=Journal of Proteome Research |volume=14 |issue=6 |pages=2539–2556 |doi=10.1021/acs.jproteome.5b00305 |pmid=25896403 |doi-access=free}}</ref><ref name = Taiwanese>{{Cite journal |last1=Liu |first1=C.-C. |last2=You |first2=C.-H. |last3=Wang |first3=P.-J. |last4=Yu |first4=J.-S. |last5=Huang|first5=G.-J. |last6=Liu |first6=C.-H. |last7=Hsieh |first7=W.-C. |last8=Lin |first8=C.-C. |date=2017 |title=Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against ''Naja kaouthia'', ''Naja siamensis'' and ''Ophiophagus hannah'' through proteomics and animal model approaches|journal=PLOS Neglected Tropical Diseases |volume=11 |issue=12 |page=e0006138 |doi=10.1371/journal.pntd.0006138 |pmid=29244815 |pmc=5747474 |doi-access=free}}</ref> The abundance is much higher than that of most [[Naja|cobras]] which is usually less than 1%.<ref>{{Cite journal |last1=Vonk |first1=F. J.|last2=Casewell |first2=N. R.|last3=Henkel |first3=C. V.|last4=Heimberg|first4=A. M. |last5=Jansen |first5=H. J.|last6=McCleary|first6=Ryan J. R.|last7=Kerkkamp|first7=Harald M. E.|last8=Vos|first8=Rutger A. |last9=Guerreiro |first9=I. |last10=Calvete |first10=J. J.|last11=Wüster |first11=W. |date=2013 |title=The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system |journal=Proceedings of the National Academy of Sciences |volume=110 |issue=51|pages=20651–20656 |doi=10.1073/pnas.1314702110 |pmid=24297900 |pmc=3870661 |bibcode=2013PNAS..11020651V |doi-access=free}}</ref> This protein family includes principal toxins responsible for [[vasculature]] damage and interference with [[haemostasis]], contributing to [[bleeding]] and [[coagulopathy]] caused by envenomation of [[vipers]]. While there are such haemorrhagins isolated from the king cobra's venom, they only induce species-sensitive haemorrhagic and lethal activities on rabbits and hares, but with minimal effects on mice.<ref name=haemorrhagins>{{Cite journal|last1=Tan|first1=N.H.|last2=Saifuddin |first2=M.N.|year=1990 |title=solation and characterization of a hemorrhagin from the venom of ''Ophiophagus hannah'' (king cobra) |journal=Toxicon |volume=28 |issue=4 |pages=385–392 |doi=10.1016/0041-0101(90)90076-j |pmid=2190359 |bibcode=1990Txcn...28..385T|doi-access=free}}</ref> Clinical pathophysiology of the king cobra's SVMPs has yet to be well studied, although its substantial quantity suggests involvement in tissue damage and necrosis as a result of inflammatory and proteolytic activities, which are instrumental for foraging and digestive purposes.<ref name = haemorrhagins/><ref name="Davidson"/>

Ohanin, a minor vespryn protein component specific to this species, causes [[hypolocomotion]] and [[hyperalgesia]] in experimental mice. It is believed that it contributes to neurotoxicity on the [[central nervous system]] of the victim.<ref>{{cite journal |author=Pung, Y. F. |author2=Kumar, S. V. |author3=Rajagopalan, N. |author4=Fry, B. G. |author5=Kumar, P. P. |author6=Kini, R. M. |pmid=16472942 |year=2006 |title=Ohanin, a novel protein from king cobra venom: Its cDNA and genomic organization |volume=371 |issue=2 |pages=246–256 |doi=10.1016/j.gene.2005.12.002 |journal=Gene}}</ref>

===Clinical management===
A king cobra's bite, and subsequent envenomation, is an immediate medical emergency in humans or domesticated animals, as, if not treated as soon as possible, death can occur in as little as 30&nbsp;minutes.<ref name="Davidson" /><ref name=Tin-MyintMyint_al1991>{{Cite journal |author=Tin-Myint |author2=Rai-Mra |author3=Maung-Chit |author4=Tun-Pe |author5=Warrell, D. |title=Bites by the king cobra (''Ophiophagus hannah'') in Myanmar: Successful treatment of severe neurotoxic envenoming |journal=The Quarterly Journal of Medicine |volume=80 |issue=293 |pages=751–762 |year=1991 |doi=10.1093/oxfordjournals.qjmed.a068624 |pmid=1754675 }}</ref> Local symptoms include dusky discolouration of skin, [[edema]] and pain; in severe cases, swelling extends proximally, with [[necrosis]] and tissue sloughing that may require amputation.<ref name="Davidson" /> Onset of general symptoms follows while the venom is targeting the victim's [[central nervous system]], resulting in blurred vision, [[Vertigo (medical)|vertigo]], [[drowsiness]], and eventual [[paralysis]]. If not treated promptly, it may progress to [[Cardiovascular system|cardiovascular]] collapse and, subsequently, [[coma]]. Death soon follows due to [[respiratory failure]], among other simultaneous and varied system and organ failures.<ref name="Davidson" />

Polyvalent [[antivenom]] of [[equine]] origin is produced by [[Haffkine Institute]] and [[King Institute of Preventive Medicine and Research]] in India.<ref>{{cite journal |author1=Whitaker, R. |author2=Whitaker, S. |year=2012 |title=Venom, antivenom production and the medically important snakes of India |journal=Current Science |volume=103 |issue=6 |pages=635–643 |url=http://www.she-india.org/wp-content/uploads/2015/03/CURRSCI_Venoms-Antivenoms-and-Snakes-of-Med-Imp_RWSW.pdf |access-date=16 October 2019 |archive-date=16 October 2019 |archive-url=https://web.archive.org/web/20191016182657/http://www.she-india.org/wp-content/uploads/2015/03/CURRSCI_Venoms-Antivenoms-and-Snakes-of-Med-Imp_RWSW.pdf |url-status=live }}</ref>
A polyvalent antivenom produced by the Thai [[Red Cross]] Society can effectively neutralise venom of the king cobra.<ref>{{cite journal |author1=Leong, P. K. |author2=Sim, S. M. |author3=Fung, S. Y. |author4=Sumana, K. |author5=Sitprija, V. |author6=Tan, N. H. |year=2012 |title=Cross Neutralization of Afro-Asian Cobra and Asian Krait Venoms by a Thai Polyvalent Snake Antivenom (Neuro Polyvalent Snake Antivenom) |journal=PLOS Neglected Tropical Diseases |volume=6 |issue=6 |page=e1672 |doi=10.1371/journal.pntd.0001672|pmid=22679522 |doi-access=free |pmc=3367981 }}</ref> In [[India]] and [[Thailand]], a [[concoction]] (or liquid blend) of [[turmeric]] (''Curcuma longa'') and other potent, medically relevant herbs reportedly creates a strong resilience against the venom of the king cobra when ingested.<ref>{{cite book |author1=Ernst, C. H. |author2=Evelyn, M. |title=Venomous Reptiles of the United States, Canada, and Northern Mexico |volume=1: Heloderma, Micruroides, Micrurus, Pelamis, Agkistrodon, Sistrurus |publisher=Johns Hopkins University Press |location=Baltimore |year=2011 |isbn=978-0-8018-9875-4 |pages=33–46 |chapter=Treatment of envenomation by reptiles |chapter-url=https://books.google.com/books?id=o8DTAQffi4UC&pg=PA44}}</ref><ref>{{cite journal |last1=Salama |first1=R. |last2=Sattayasai |first2=J. |last3=Gande |first3=A. K. |last4=Sattayasai |first4=N. |last5=Davis |first5=M. |last6=Lattmann |first6=E. |year=2012 |title=Identification and evaluation of agents isolated from traditionally used herbs against ''Ophiophagus hannah'' venom |journal=Drug Discoveries & Therapeutics |volume=6 |issue=1 |pages=18–23 |pmid=22460424}}</ref> Proper and immediate treatments are critical to avoid death. Successful precedents include a client who recovered and was discharged in 10&nbsp;days after being treated by accurate antivenom and [[inpatient care]].<ref name=Tin-MyintMyint_al1991/>

It can deliver up to 420&nbsp;mg venom in dry weight (400–600&nbsp;mg overall) per bite,<ref name="LD50"/> with a {{LD50}} toxicity in mice of 1.28&nbsp;mg/kg through [[intravenous injection]],<ref>{{cite journal |author=Ganthavorn, S. |year=1969 |title=Toxicities of Thailand snake venoms and neutralization capacity of antivenin |journal=Toxicon |volume=7 |issue=3 |pages=239–241 |doi=10.1016/0041-0101(69)90012-9 |pmid=5358069|bibcode=1969Txcn....7..239G }}</ref> 1.5 to 1.7&nbsp;mg/kg through [[subcutaneous injection]],<ref>{{cite journal |author1=Broad, A. J. |author2=Sutherland, S. K. |author3=Coulter, A. R. |year=1979 |title=The lethality in mice of dangerous Australian and other snake venom |journal=Toxicon |volume=17 |issue=6 |pages=661–664 |url=http://www.kingsnake.com/aho/pdf/menu5/broad1979b.pdf |doi=10.1016/0041-0101(79)90245-9 |pmid=524395 |bibcode=1979Txcn...17..661B |access-date=14 October 2019 |archive-date=31 March 2022 |archive-url=https://web.archive.org/web/20220331091804/http://www.kingsnake.com/aho/pdf/menu5/broad1979b.pdf |url-status=live}}</ref>
and 1.644&nbsp;mg/kg through [[intraperitoneal injection]].<ref name=LD50>{{cite web |author=Thomas, S. |author2=Griessel, E. |date=1999 |url=http://www.seanthomas.net/oldsite/ld50tot.html |title=LD50 (Archived) |url-status=dead |archive-url=https://web.archive.org/web/20120201062634/http://www.seanthomas.net/oldsite/ld50tot.html |archive-date=1 February 2012}}</ref><ref name=Engelmann>{{cite book |last=Engelmann |first=W.-E. |title=Snakes: Biology, Behavior, and Relationship to Man |year=1981 |publisher=Leipzig Publishing; English version published by Exeter Books (1982) |location=Leipzig; English version NY, USA |isbn=0-89673-110-3 |page=222 |url=https://archive.org/details/snakesbiologybeh0000enge/page/222}}</ref><ref name="CRC Press">{{cite book |title=Handbook of clinical toxicology of animal venoms and poisons |publisher=CRC Press |volume=236 |year=1995 |location=USA |isbn=0-8493-4489-1}}</ref> For research purposes, up to 1 g of venom was obtained through milking.<ref name=Malaysian>{{Cite journal |last1=Tan |first1=C. H. |last2=Tan |first2=K. Y. |last3=Fung |first3=S. Y. |last4=Tan|first4=N. H. |date=2015 |title=Venom-gland transcriptome and venom proteome of the Malaysian king cobra (''Ophiophagus hannah'')|journal=BMC Genomics |volume=16 |issue=1 |page=687 |doi=10.1186/s12864-015-1828-2 |pmid=26358635 |pmc=4566206|doi-access=free}}</ref>