The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins

Kushal Suryamohan,Leonard D Goldstein,Oommen K Mathew,Markus S Schröder,Hiroki Shibata,Aju Antony,Domagoj Vucic,Ying Jiun J Chen ,Aakrosh Ratan,Sangeetha Mohan,Kristen Wiley,Jeremy Stinson,Terje Raudsepp,Donald S Kirkpatrick,Derek Vargas,Sajesh P Krishnankutty ,Megha Muraleedharan,Eric Stawiski ,Mandumpala Davis Dixon,Boney Kuriakose,Dinesh Velayutham,Joseph Guillory,Matthew Jevit,Zora Modrušan ,Ridhi Goel,Kate Senger,Subhra Chaudhuri,R Manjunatha Kini,Guillermo De La Rosa,Ivan Koludarov,Meng Wu,James Ziai,Rajadurai Chinnasamy Perumal ,Steffen Durinck,Brendan K Faherty ,Miriam Baca,Rami N Hannoush,Peter Liu,Gus A Wright,Meredith Sagolla,Arun Zachariah,Somasekar Seshagiri

doi:10.1038/s41588-019-0559-8

Kushal Suryamohan, Leonard D Goldstein + Show 40 more

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https://doi.org/10.1038/s41588-019-0559-8

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Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the ‘venom-ome’ and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 ‘venom-ome-specific toxins’ (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery.

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Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually
Fossil remains from ~100 million years ago (Ma) show that snakes were widely distributed across the world by the late Cretaceous period[1]
Since 1896, antivenom has been developed by immunization of large mammals, such as the horse, with snake venom to generate a cocktail of antibodies that are used for therapy[12]

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Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the ‘venom-ome’ and this included 139 genes from 33 toxin families. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Snakebite envenoming is a serious neglected tropical disease that affects ~5 million people worldwide annually, leading to ~400,000 amputations and >100,000 deaths[6]. In India alone, the high rural population density combined with the presence of the ‘big four’ deadly snakes, namely the Indian cobra (Naja naja), Russell’s viper (Daboia russelli), sawscaled viper (Echis carinatus) and common krait (Bungarus caeruleus), results in >46,000 snakebite-related deaths annually[7]. Since 1896, antivenom has been developed by immunization of large mammals, such as the horse, with snake venom to generate a cocktail of antibodies that are used for therapy[12]. The antivenom composition is not well defined and its ability to neutralize the venom

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