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

• Main Authors: Wong, Kin Ying, Tan, Kae Yi, Tan, Nget Hong, Gnanathasan, Christeine Ariaranee, Tan, Choo Hock
• Format: Article
• Published: MDPI 2021
• Subjects: RA0421 Public health. Hygiene. Preventive Medicine; Pharmacopoeia
• Online Access: http://eprints.um.edu.my/27878/
• Institution: Universiti Malaya

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.