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The preclinical evaluation of a second-generation antivenom for treating snake envenoming in India

ABSTRACT: In this study, by employing chromatographic purification of the bulk, we have significantly enhanced the preclinical performance of the conventional Indian antivenom product. The effectiveness of the test batches of this ‘second-generation’ antivenom was evaluated using a variety of in vitro and in vivo preclinical assays, including venom recognition and toxicity and pathology neutralisation. The outcomes of these experiments demonstrated the significantly superior performance of the purified product over all other major commercial Indian antivenoms.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Equus Caballus (horse)

TISSUE(S): Blood Serum

SUBMITTER: Kartik Sunagar

LAB HEAD: Dr. Kartik Sunagar

PROVIDER: PXD029436 | Pride | 2022-04-04

REPOSITORIES: Pride

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			Action	DRS
	Premium.pep.xml	Pepxml
	Premium.raw	Raw
	SIIPL01.pep.xml	Pepxml
	SIIPL1.raw	Raw
	Virchow.pep.xml	Pepxml

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Publications

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

Attarde Saurabh S Iyer Ashwin A Khochare Suyog S Shaligram Umesh U Vikharankar Mayur M Sunagar Kartik K

Toxins 20220224 3

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 ...[more]

PMID: 35324665

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Fangs in the ghats: preclinical insights into the medical importance of endemic pit vipers from the Western Ghats

Project description:The socioeconomic burden of snakebite in India is largely attributed to the ‘big four’ snakes, completely neglecting the considerable impact of envenoming by many other snake species. Bites from the so-called ‘neglected many’ are often treated with a polyvalent antivenom that is manufactured against the ‘big four’ snakes - a strategy that has been widely documented to fail. Yet, specific antivenoms are not commercially manufactured against these snakes. While the medical importance of various species of cobras, saw-scaled vipers, and kraits is very well-known, the clinical impact of pit vipers from the rainforests of the Western Ghats, northeastern India, and Andaman and Nicobar islands has remained elusive. Amongst the 90+ species of snakes found in the Western Ghats, the hump-nosed (Hypnale hypnale), Malabar (Craspedocephalus malabaricus) and bamboo (Craspedocephalus gramineus) pit vipers can potentially inflict clinically severe envenoming in humans. To evaluate the severity of toxicity inflicted by these snakes, we characterised their venom composition, biochemical and pharmacological activities, and toxicity- and morbidity-inducing potentials. Our findings highlight the therapeutic inadequacies of the generic Indian and Hypnale-specific Sri Lankan polyvalent antivenoms in neutralising morbidity and mortality resulting from pit viper envenomings and underscore the need for a regional antivenom therapy in India.

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Geographical origin and antigenicity of venom. Intraspecies proteomic and immunological analysis of Naja mossambica venom. 2DE-LC/MS approach

Project description:The main objective of the project is to find the reason why antivenoms commonly used in treatments of Naja mossambica bites are not effective in Eswatini and Mozambique, whereas they exhibit normal activity in other countries of southern Africa. The main hypothesis here assumes that intra-species differences in protein composition of venoms from different part of the continent are the main cause of observed diversity in antivenom efficacy. In the course of the project, there is also a plan to identify the specific toxins that differ analyzed venoms in reactivity towards antivenom immunoglobulins.

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Geographical origin and antigenicity of venom. Intraspecies proteomic and immunological analysis of Naja mossambica venom.

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Proteomic and toxinological characterization of the venom from Peruvian Andes Crotalus durissus.

Project description:The present study performed the proteomic and biological activities of Peruvian Crotalus durissus, an endangered species reported to cause neuro and myotoxic symptoms. Due to the severity of its envenomation and to its geographical location, Peruvian Crotalus durissus is considered of public health importance in Peru. Snakebite treatment depends on rapid administration of appropriate antivenom. In this sense, the recognition of Peruvian Crotalus durissus venom (PCdV) by Brazilian and Peruvian antivenoms was tested. The results of this study increase the scarce knowledge about PCdV composition and demonstrate antivenom recognition of PCdV proteins, indicating a possible efficiency of these antivenoms to treat Peruvian Crotalus durissus accidents

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A phenotype-based model for rational selection of novel targeted therapies in treating aggressive breast cancer

Project description:Treating unselected cancer patients with new drugs dilutes proof of efficacy when only a fraction of patients respond to therapy. We conducted a meta-analysis on eight primary breast cancer microarray datasets representing diverse breast cancer phenotypes. We present a high-throughput protocol which incorporates drug sensitivity signatures to guide preclinical testing for effective therapeutic agents. Specifically, we focus on drug classes currently undergoing early phase clinical testing. Our genomic and experimental results suggest that the majority of basal-like breast cancers should respond to inhibitors of the phosphatidylinositol-3-kinase pathway, and that a relatively low toxicity histone deacetylase inhibitor, valproic acid, may target aggressive breast cancers. For a subset of drugs, prediction of sensitivity associates with tumor recurrence, suggesting clinical relevance. Preclinical studies using both cell lines and patient tumors grown in 3-dimensional in vitro and orthotopic in vivo preclinical models provide an efficient and highly relevant assessment of drug sensitivity in tumor phenotypes, and validate our genomic analyses. Together, our results show that high-throughput transcriptional profiling can significantly impact drug selection for breast cancer patients. Pre-identification of patient response may not only improve therapeutic response rates, it can also assist in quickly identifying the optimal inclusion criteria for clinical trials. Our model facilitates personalized drug therapy for cancer patients and may be generalized for study of drug efficacy in other diseases. Breast cancer pleural effusion samples from triple negative patients. Compared samples that are computationally predicted to be sensitive to valproic acid and those that are not predicted to be sensitive.

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