干旱区生态环境知识资源中心(Arid): Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots

Arid

DOI	10.1371/journal.pntd.0009247
	Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots
	Laxme, R. R. Senji; Khochare, Suyog; Attarde, Saurabh; Suranse, Vivek; Iyer, Ashwin; Casewell, Nicholas R.; Whitaker, Romulus; Martin, Gerard; Sunagar, Kartik
通讯作者	Sunagar, K (corresponding author), Indian Inst Sci, Evolutionary Ven Lab, Ctr Ecol Sci, Bangalore, Karnataka, India.
来源期刊	PLOS NEGLECTED TROPICAL DISEASES
ISSN	1935-2735
出版年	2021
卷号	15 期号:3
英文摘要	Background Snakebite in India results in over 58,000 fatalities and a vast number of morbidities annually. The majority of these clinically severe envenomings are attributed to Russell's viper (Daboia russelii), which has a near pan-India distribution. Unfortunately, despite its medical significance, the influence of biogeography on the composition and potency of venom from disparate D. russelii populations, and the repercussions of venom variation on the neutralisation efficacy of marketed Indian antivenoms, remain elusive. Methods Here, we employ an integrative approach comprising proteomic characterisation, biochemical analyses, pharmacological assessment, and venom toxicity profiling to elucidate the influence of varying ecology and environment on the pan-Indian populations of D. russelii. We then conducted in vitro venom recognition experiments and in vivo neutralisation assays to evaluate the efficacy of the commercial Indian antivenoms against the geographically disparate D. russelii populations. Findings We reveal significant intraspecific variation in the composition, biochemical and pharmacological activities and potencies of D. russelii venoms sourced from five distinct biogeographic zones across India. Contrary to our understanding of the consequences of venom variation on the effectiveness of snakebite therapy, commercial antivenom exhibited surprisingly similar neutralisation potencies against the majority of the investigated populations, with the exception of low preclinical efficacy against the semi-arid population from northern India. However, the ability of Indian antivenoms to counter the severe morbid effects of Daboia envenoming remains to be evaluated. Conclusion The concerning lack of antivenom efficacy against the north Indian population of D. russelii, as well as against two other 'big four' snake species in nearby locations, underscores the pressing need to develop pan-India effective antivenoms with improved efficacy in high snakebite burden locales. Author summary The Russell's viper (Daboia russelii), with a near-countrywide distribution, is arguably the deadliest snake species in India. Despite being responsible for the majority of snakebite deaths in the country, the influence of biogeography on its venom composition and potency, and the impact of this variation on snakebite therapy, is yet to be understood. Evaluation of the composition, biochemical activities, pharmacological implications and potencies of D. russelii venoms from five distinct biogeographic zones in India (>5,800 km) revealed remarkable intraspecific differences in venom profiles. Surprisingly, these observed differences did not seem to affect the marketed effectiveness of the commercial Indian antivenoms in countering the lethal effects of D. russelii venoms, with the exception of the North Indian semi-arid population. A similar lack of antivenom potency has also been documented in two other 'big four' snake species in these regions that suffer the brunt of snakebite. These alarming findings underscore the pressing need to develop pan-India efficacious antivenoms, especially for the treatment of snakebites in regions that are worst affected by this neglected tropical disease.
类型	Article
语种	英语
开放获取类型	Green Published, gold, Green Accepted
收录类别	SCI-E
WOS记录号	WOS:000634794600003
WOS关键词	PHOSPHOLIPASE A(2) ; PROTEOMIC ANALYSIS ; DNASE ACTIVITY ; PURIFICATION ; NEUTRALIZATION ; NEUROTOXIN ; POLYVALENT ; HEMOLYSIS ; ALPHA ; BETA
WOS类目	Infectious Diseases ; Parasitology ; Tropical Medicine
WOS研究方向	Infectious Diseases ; Parasitology ; Tropical Medicine
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/368970
作者单位	[Laxme, R. R. Senji; Khochare, Suyog; Attarde, Saurabh; Suranse, Vivek; Iyer, Ashwin; Sunagar, Kartik] Indian Inst Sci, Evolutionary Ven Lab, Ctr Ecol Sci, Bangalore, Karnataka, India; [Casewell, Nicholas R.] Univ Liverpool Liverpool Sch Trop Med, Ctr Snakebite Res & Intervent, Pembroke Pl, Liverpool, Merseyside, England; [Whitaker, Romulus] Madras Crocodile Bank Trust, Ctr Herpetol, East Coast Rd, Mamallapuram, Tamil Nadu, India; [Martin, Gerard] Liana Trust, Survey 1418-1419 Rathnapuri, Hunsur, Karnataka, India
推荐引用方式 GB/T 7714	Laxme, R. R. Senji,Khochare, Suyog,Attarde, Saurabh,et al. Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots[J],2021,15(3).
APA	Laxme, R. R. Senji.,Khochare, Suyog.,Attarde, Saurabh.,Suranse, Vivek.,Iyer, Ashwin.,...&Sunagar, Kartik.(2021).Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots.PLOS NEGLECTED TROPICAL DISEASES,15(3).
MLA	Laxme, R. R. Senji,et al."Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots".PLOS NEGLECTED TROPICAL DISEASES 15.3(2021).