Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom

Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron’s Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-l...

Full description

Bibliographic Details
Main Authors: Tan, Choo Hock, Tan, Kae Yi, Ng, Tzu Shan, Quah, Evan S.H., Ismail, Ahmad Khaldun, Khomvilai, Sumana, Sitprija, Visith, Tan, Nget Hong
Format: Article
Published: MDPI 2019
Subjects:
_version_ 1825722039124623360
author Tan, Choo Hock
Tan, Kae Yi
Ng, Tzu Shan
Quah, Evan S.H.
Ismail, Ahmad Khaldun
Khomvilai, Sumana
Sitprija, Visith
Tan, Nget Hong
author_facet Tan, Choo Hock
Tan, Kae Yi
Ng, Tzu Shan
Quah, Evan S.H.
Ismail, Ahmad Khaldun
Khomvilai, Sumana
Sitprija, Visith
Tan, Nget Hong
author_sort Tan, Choo Hock
collection UM
description Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron’s Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. Snake venom metalloproteinases (SVMP) dominated the venom proteome by 48.42% of total venom proteins, with a characteristic distribution of P-III: P-II classes in a ratio of 2:1, while P-I class was undetected. Snaclecs constituted the second most venomous protein family (19.43%), followed by snake venom serine proteases (SVSP, 14.27%), phospholipases A 2 (5.40%), disintegrins (5.26%) and minor proteins including cysteine-rich secretory proteins, L-amino acid oxidases, phosphodiesterases, 5 ′ -nucleotidases. The venomic profile correlates with local (painful progressive edema) and systemic (hemorrhage, coagulopathy, thrombocytopenia) manifestation of T. nebularis envenoming. As specific antivenom is unavailable for T. nebularis, the hetero-specific Thai Green Pit viper Monovalent Antivenom (GPVAV) was examined for immunological cross-reactivity. GPVAV exhibited good immunoreactivity to T. nebularis venom and the antivenom effectively cross-neutralized the hemotoxic and lethal effects of T. nebularis (lethality neutralizing potency = 1.6 mg venom per mL antivenom). The findings supported GPVAV use in treating T. nebularis envenoming. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
first_indexed 2024-03-06T05:59:33Z
format Article
id um.eprints-23324
institution Universiti Malaya
last_indexed 2024-03-06T05:59:33Z
publishDate 2019
publisher MDPI
record_format dspace
spelling um.eprints-233242020-01-06T03:37:36Z http://eprints.um.edu.my/23324/ Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom Tan, Choo Hock Tan, Kae Yi Ng, Tzu Shan Quah, Evan S.H. Ismail, Ahmad Khaldun Khomvilai, Sumana Sitprija, Visith Tan, Nget Hong R Medicine Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron’s Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. Snake venom metalloproteinases (SVMP) dominated the venom proteome by 48.42% of total venom proteins, with a characteristic distribution of P-III: P-II classes in a ratio of 2:1, while P-I class was undetected. Snaclecs constituted the second most venomous protein family (19.43%), followed by snake venom serine proteases (SVSP, 14.27%), phospholipases A 2 (5.40%), disintegrins (5.26%) and minor proteins including cysteine-rich secretory proteins, L-amino acid oxidases, phosphodiesterases, 5 ′ -nucleotidases. The venomic profile correlates with local (painful progressive edema) and systemic (hemorrhage, coagulopathy, thrombocytopenia) manifestation of T. nebularis envenoming. As specific antivenom is unavailable for T. nebularis, the hetero-specific Thai Green Pit viper Monovalent Antivenom (GPVAV) was examined for immunological cross-reactivity. GPVAV exhibited good immunoreactivity to T. nebularis venom and the antivenom effectively cross-neutralized the hemotoxic and lethal effects of T. nebularis (lethality neutralizing potency = 1.6 mg venom per mL antivenom). The findings supported GPVAV use in treating T. nebularis envenoming. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. MDPI 2019 Article PeerReviewed Tan, Choo Hock and Tan, Kae Yi and Ng, Tzu Shan and Quah, Evan S.H. and Ismail, Ahmad Khaldun and Khomvilai, Sumana and Sitprija, Visith and Tan, Nget Hong (2019) Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom. Toxins, 11 (2). p. 95. ISSN 2072-6651, DOI https://doi.org/10.3390/toxins11020095 <https://doi.org/10.3390/toxins11020095>. https://doi.org/10.3390/toxins11020095 doi:10.3390/toxins11020095
spellingShingle R Medicine
Tan, Choo Hock
Tan, Kae Yi
Ng, Tzu Shan
Quah, Evan S.H.
Ismail, Ahmad Khaldun
Khomvilai, Sumana
Sitprija, Visith
Tan, Nget Hong
Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom
title Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom
title_full Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom
title_fullStr Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom
title_full_unstemmed Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom
title_short Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom
title_sort venomics of trimeresurus popeia nebularis the cameron highlands pit viper from malaysia insights into venom proteome toxicity and neutralization of antivenom
topic R Medicine
work_keys_str_mv AT tanchoohock venomicsoftrimeresuruspopeianebularisthecameronhighlandspitviperfrommalaysiainsightsintovenomproteometoxicityandneutralizationofantivenom
AT tankaeyi venomicsoftrimeresuruspopeianebularisthecameronhighlandspitviperfrommalaysiainsightsintovenomproteometoxicityandneutralizationofantivenom
AT ngtzushan venomicsoftrimeresuruspopeianebularisthecameronhighlandspitviperfrommalaysiainsightsintovenomproteometoxicityandneutralizationofantivenom
AT quahevansh venomicsoftrimeresuruspopeianebularisthecameronhighlandspitviperfrommalaysiainsightsintovenomproteometoxicityandneutralizationofantivenom
AT ismailahmadkhaldun venomicsoftrimeresuruspopeianebularisthecameronhighlandspitviperfrommalaysiainsightsintovenomproteometoxicityandneutralizationofantivenom
AT khomvilaisumana venomicsoftrimeresuruspopeianebularisthecameronhighlandspitviperfrommalaysiainsightsintovenomproteometoxicityandneutralizationofantivenom
AT sitprijavisith venomicsoftrimeresuruspopeianebularisthecameronhighlandspitviperfrommalaysiainsightsintovenomproteometoxicityandneutralizationofantivenom
AT tanngethong venomicsoftrimeresuruspopeianebularisthecameronhighlandspitviperfrommalaysiainsightsintovenomproteometoxicityandneutralizationofantivenom