Elucidating the venom diversity in Sri Lankan spectacled cobra (Naja naja) through de novo venom gland transcriptomics, venom proteomics and toxicity neutralization

Wong, Kin Ying and Tan, Kae Yi and Tan, Nget Hong and Gnanathasan, Christeine Ariaranee and Tan, Choo Hock (2021) Elucidating the venom diversity in Sri Lankan spectacled cobra (Naja naja) through de novo venom gland transcriptomics, venom proteomics and toxicity neutralization. Toxins, 13 (8). ISSN 2072-6651, DOI https://doi.org/10.3390/toxins13080558.

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Abstract

Inadequate effectiveness of Indian antivenoms in treating envenomation caused by the Spectacled Cobra/Indian Cobra (Naja naja) in Sri Lanka has been attributed to geographical variations in the venom composition. This study investigated the de novo venom-gland transcriptomics and venom proteomics of the Sri Lankan N. naja (NN-SL) to elucidate its toxin gene diversity and venom variability. The neutralization efficacy of a commonly used Indian antivenom product in Sri Lanka was examined against the lethality induced by NN-SL venom in mice. The transcriptomic study revealed high expression of 22 toxin genes families in NN-SL, constituting 46.55% of total transcript abundance. Three-finger toxins (3FTX) were the most diversely and abundantly expressed (87.54% of toxin gene expression), consistent with the dominance of 3FTX in the venom proteome (72.19% of total venom proteins). The 3FTX were predominantly S-type cytotoxins/cardiotoxins (CTX) and alpha-neurotoxins of long-chain or short-chain subtypes (alpha-NTX). CTX and alpha-NTX are implicated in local tissue necrosis and fatal neuromuscular paralysis, respectively, in envenomation caused by NN-SL. Intra-species variations in the toxin gene sequences and expression levels were apparent between NN-SL and other geographical specimens of N. naja, suggesting potential antigenic diversity that impacts antivenom effectiveness. This was demonstrated by limited potency (0.74 mg venom/ml antivenom) of the Indian polyvalent antivenom (VPAV) in neutralizing the NN-SL venom. A pan-regional antivenom with improved efficacy to treat N. naja envenomation is needed.

Item Type: Article
Funders: Ministry of Education, Malaysia [FRGS/1/2019/SKK08/UM/02/2], Universiti Malaya [BKS003-2020]
Uncontrolled Keywords: Indian cobra; Venomics; Venom-induced toxicity; Antivenom; Neutralization
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
R Medicine > RS Pharmacy and materia medica > Pharmacopoeia
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 07 Apr 2022 07:25
Last Modified: 12 Apr 2022 06:50
URI: http://eprints.um.edu.my/id/eprint/27878

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