Remarkable intrapopulation venom variability in the monocellate cobra (Naja kaouthia) unveils neglected aspects of India's snakebite problem

Rashmi, U.; Khochare, Suyog; Attarde, Saurabh; Laxme, R. R. Senji; Suranse, Vivek; Martin, Gerard; Sunagar, Kartik

doi:10.1016/j.jprot.2021.104256

Cited by 21 publications

(30 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, these findings highlight the importance of utilising simpler chromatographic purification steps for the manufacture of commercial antivenoms. Conventional Indian antivenoms, which have a lower proportion of venom toxin-binding and neutralising antibodies [ 3 , 4 , 8 , 10 , 12 , 13 ] and a higher load of impurities, often result in severe secondary reactions to the antivenom, including serum sickness and fatal anaphylaxis [ 14 ]. Hence, the improvements in the purity and overall quality of the antivenom product achieved here are anticipated to greatly reduce such undesirable effects.…”

Section: Discussionmentioning

confidence: 99%

“…Conventional antivenoms that are manufactured by hyperimmunising equines are the only effective treatment for snakebites [ 2 ]. However, commercial Indian antivenoms have been documented to exhibit a poor preclinical efficacy in neutralising venom due to inter- and intrapopulation venom variation in targeted species [ 3 , 4 , 5 , 6 , 7 ], as well as closely related and medically important yet neglected snakes (a.k.a., the ‘neglected many’) [ 8 , 9 , 10 , 11 , 12 , 13 ]. They are also known to exhibit a poor dose efficacy, resulting in the need for larger volumes of antivenom doses in order to effect a cure.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India

Attarde

Iyer

Khochare

et al. 2022

Toxins

Self Cite

View full text Add to dashboard Cite

Snake envenoming afflicts the Indian subcontinent with the highest rates of mortality (47,000) and morbidity globally. The only effective treatment for snakebites is the administration of antivenom, which is produced by the hyperimmunisation of equines. Commercial Indian antivenoms, however, have been shown to exhibit a poor preclinical performance in neutralising venom, as a result of inter- and intrapopulation snake venom variation. Additionally, their poor dose effectiveness necessitates the administration of larger volumes of antivenom for treatment, leading to several harmful side effects in snakebite victims, including serum sickness and fatal anaphylaxis. In this study, we employed chromatographic purification to enhance the dose efficacy of commercial Indian antivenoms. The efficacy of this ‘second-generation’ antivenom was comparatively evaluated against six other marketed antivenoms using a number of in vitro and in vivo preclinical assays, which revealed its superior venom recognition capability. Enhanced purity also resulted in significant improvements in dose effectiveness, as the ‘second-generation’ antivenom exhibited a 3 to 4.5 times increased venom neutralisation potential. Furthermore, preclinical assays revealed the increased effectiveness of the ‘second-generation’ antivenom in countering morbid effects inflicted by the ‘big four’ Indian snakes. Thus, we demonstrate the role of simpler purification steps in significantly enhancing the effectiveness of snakebite therapy in regions that are most affected by snakebites.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India

Attarde

Iyer

Khochare

et al. 2022

Toxins

Self Cite

View full text Add to dashboard Cite

show abstract

“…As a consequence of local adaptation to shifts in ecology and environment, stark inter and intraspecific differences in venom composition and toxicity profiles have been observed in snakes ( Daltry et al, 1996 ; Sunagar et al, 2014 ; Rokyta et al, 2017 ; Casewell et al, 2020 ; Senji Laxme RR. et al, 2021 ; Senji Laxme R. R. et al, 2021 ), even within a restricted geographic locale ( Rashmi et al, 2021 ). Consistently, the characterisation of venom proteomes in this study revealed considerable differences in the venoms of N. naja and N. sagittifera .…”

Section: Discussionmentioning

confidence: 99%

“…The RP-HPLC fractions of N. sagittifera and N. naja venom were subjected to in-solution trypsin digestion, followed by lyophilisation and storage at −80°C. The samples were then reconstituted moments before injection and characterisation with tandem mass spectrometry ( Rashmi et al, 2021 ). Samples (40 µg) were first reduced with 10 mM dithiothreitol (DTT), alkylated using 30 mM iodoacetamide (IAA) and further digested with trypsin (0.2 µg/µl) overnight at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…The redundant protein hits from each protein family were removed manually, and their relative abundance in a fraction was determined by calculating its area under the spectral intensity curve (AUC) relative to the overall AUC for all protein families in that fraction. AUC values obtained from PEAKS Studio analyses, representing the mean spectral intensities, were normalised across fractions using the percentage of peak areas for the respective RP-HPLC fractions ( Tan et al, 2017 ; Rashmi et al, 2021 ). The relative abundance of a protein family hit (X) was estimated using the equation below, where “N” indicates the total number of fractions obtained from RP-HPLC and “n” corresponds to the fraction number.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Venomics of the Enigmatic Andaman Cobra (Naja sagittifera) and the Preclinical Failure of Indian Antivenoms in Andaman and Nicobar Islands

et al. 2021

Self Cite

View full text Add to dashboard Cite

The Andaman and Nicobar Islands are an abode to a diversity of flora and fauna, including the many endemic species of snakes, such as the elusive Andaman cobra (Naja sagittifera). However, the ecology and evolution of venomous snakes inhabiting these islands have remained entirely uninvestigated. This study aims to bridge this knowledge gap by investigating the evolutionary history of N. sagittifera and its venom proteomic, biochemical and toxicity profile. Phylogenetic reconstructions confirmed the close relationship between N. sagittifera and the Southeast Asian monocellate cobra (N. kaouthia). Overlooking this evolutionary history, a polyvalent antivenom manufactured using the venom of the spectacled cobra (N. naja) from mainland India is used for treating N. sagittifera envenomations. Comparative evaluation of venoms of these congeners revealed significant differences in their composition, functions and potencies. Given the close phylogenetic relatedness between N. sagittifera and N. kaouthia, we further assessed the cross-neutralising efficacy of Thai monovalent N. kaouthia antivenom against N. sagittifera venoms. Our findings revealed the inadequate preclinical performance of the Indian polyvalent and Thai monovalent antivenoms in neutralising N. sagittifera venoms. Moreover, the poor efficacy of the polyvalent antivenom against N. naja venom from southern India further revealed the critical need to manufacture region-specific Indian antivenoms.

show abstract

Systematic review and meta-analysis on the efficacy of Indian polyvalent antivenom against the Indian snakes of clinical significance

Gopal,

Selvaraj,

Venkataramanan

et al. 2023

Arch Toxicol

View full text Add to dashboard Cite

Remarkable intrapopulation venom variability in the monocellate cobra (Naja kaouthia) unveils neglected aspects of India's snakebite problem

Cited by 21 publications

References 74 publications

The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India

The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India

Venomics of the Enigmatic Andaman Cobra (Naja sagittifera) and the Preclinical Failure of Indian Antivenoms in Andaman and Nicobar Islands

Systematic review and meta-analysis on the efficacy of Indian polyvalent antivenom against the Indian snakes of clinical significance

Contact Info

Product

Resources

About