Monday, November 15, 2010

Hamadryad Research

 A number of recent papers have expanded our knowledge of the King Cobra, or Hamadryad, (Ophiophagus hannah), here a few that have appeared during 2010.

Bashir, et al. (2010) reports the sighting of the King Cobra from Yuksam village (27022’12.5’’N and 88013’27.0’’E). The village borders the Khangchendzonga Biosphere Reserve in the West District of Sikkim, India. The snake was observed in a drain adjoining human settlement (at an altitude of 1820 m) on 6 December 2009 at 0805 hr. The snake was estimated to be about 3−3.5 m. A few days later, the snake was seen basking on a rock near bamboo thickets adjoining the lake. There are two highlights: the new altitude record of 1840 m. for the northeast portion of the range; and, the fact that the snake was using the transitional forest between subtropical broadleaved evergreen forest and temperate forests. The species has not been previously reported from this Sikkim environment. Previously it was reported from Gangtok at 1700m in 1923 and was believed to be limited to the tropical forests of Sikkim Himalaya which are found below 1250 m. The highest known altitude record for the Hamadryad in northeastern India was 1700m at Khonoma, Nagaland (Das et al. 2008). 

Superimposition of haditoxin subunit A (blue) with erabutoxin-a (magenta), erabutoxin-b (cyan), and toxin-α (green), which highlights haditoxin's three-finger protein fold and its resemblance to other short-chain α-neurotoxins.
Chen and Lai (2010) from the Guangzhou University of Chinese Medicine sequenced the complete mitochondrial genome of King Cobra (GenBank accession number: EU_921899) by Ex Taq-PCR, TA-cloning and primer-walking methods. The cobra’s genome is similar to other vertebrate. It is 17 267 bp in length and encodes 38 genes (including 13 protein-coding, 2 ribosomal RNA and 23 transfer RNA genes) and it contains two, long, non-coding regions. This data demonstrated that Elapidae is more closely related to Colubridae (=Colubroidae) than Viperidae, supporting previous work.

Zedoary (Curcuma zedoaria, family Zingiberaceae) is a plant native to South and Southeast Asia and it was introduced into Europe sometime in the sixth century, and while it is used as a spice it is rare, having been replaced by ginger. It is commonly used in the northeastern Thailand as a snakebite remedy. Lattmann, et al. (2010) isolated the active compound from the rhizome of C. zedoaroides, determined its structure and assessed its antagonistic properties against King Cobra venom. The acetone extract from the rhizomes of Curcuma rhizomes contained a C20 dialdehyde, as the major component. The isolated curcuma dialdehyde was to be found active in both in vitro and in vivo tests for antivenin activity against King Cobra venom. Using isolated rat phrenic nerve-hemidiaphragm preparations, the researchers found a significant antagonistic effect on the inhibition of neuromuscular transmission and muscle contractions were inhibited by the venom, and found they could reversed it with Curcuma dialdehyde in organ bath preparations over a period of 2 hours. Mice injected with 0.75 mg/kg venom and the dialdehyde had a significantly increased survival time. Injection of the Curcuma dialdehyde 30 minutes before the subcutaneous injection of the venom resulted in a 100% survival time after 2 h compared with 0% for the control group. Thus the in vitro and in vivo evaluation confirmed the medicinal use of Zedoary against King Cobra venom. 

Roy et al. (2010) have described haditoxin, a novel peptide from the venom of Ophiophagus. They provide a detailed structural and functional characterization of this unusual neurotoxin. Using a 1.5 Å crystal structure, they found haditoxin exists as a homodimer, similar to the κ-neurotoxin family, but the monomeric subunits of haditoxin, consist of a three-finger protein fold closely resembling a short-chain α-neurotoxins, unlike κ-neurotoxin monomers, which resemble long-chain α-neurotoxins. While haditoxin could antagonize several classes of nicotinic acetylcholine receptors in neurons and muscle, its greatest potency was against receptors, which neiher recognized by short-chain α-neurotoxins or κ-neurotoxins. Thus haditoxin might have many future uses in developing molecular probes and therapeutic agents.

Bashir, T., K. Poudyal, T. Bhattacharya, S. Sathyakumar & J.B. Subba, 2010. Sighting of King Cobra Ophiophagus hannah in Sikkim, India: a new altitude record for the northeast. Journal of Threatened Taxa 2(6): 990-991.
Chen N. and X. P. Lai. 2010. [Sequencing and analysis of the complete mitochondrial genome of the King Cobra, Ophiophagus hannah (Serpents: Elapidae)] [Article in Chinese]. Yi Chan 32(7):719-25.

Lattmann, E., J. Sattayasai,, N. Sattayasai, A. Staaf, S. Phimmasone, C. H. Schwalbe, and A. Chaveerach. 2010. In-vitro and in-vivo antivenin activity of 2-[2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde against Ophiophagus hannah venom. Journal of Pharmacy and Pharmacology, 62:257–262. doi: 10.1211/jpp.62.02.0014

Roy, A., X. Zhou, M. Z. Chong, D. D'hoedt, C. S. Foo, N. Rajagopalan, S. Nirthanan, D. Bertrand, J. Sivaraman, and R. Manjunatha Kini. 2010. Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra) Journal of Biological Chemistry 285: 8302-8315.

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