Harnessing the Cross-Neutralisation Potential of Existing Antivenoms for Mitigating the Outcomes of Snakebite in Sub-Saharan Africa.

Over 32,000 individuals succumb to snake envenoming in sub-Saharan Africa (sSA) annually. This results from several factors, including a lack of antivenom products capable of neutralising the venoms of diverse snake species in this region. Most manufacturers produce polyvalent antivenoms targeting 3 to 16 clinically important snake species in sSA. However, specific products are unavailable for many others, especially those with a restricted geographic distribution. While next-generation antivenoms, comprising a cocktail of broadly neutralising antibodies, may offer an effective solution to this problem, given the need for their clinical validation, recombinant antivenoms are far from being available to snakebite victims. One of the strategies that could immediately address this issue involves harnessing the cross-neutralisation potential of existing products. Therefore, we assessed the neutralisation potency of PANAF-Premium antivenom towards the venoms of 14 medically important snakes from 13 countries across sSA for which specific antivenom products are unavailable. Preclinical assays in a murine model of snake envenoming revealed that the venoms of most snake species under investigation were effectively neutralised by this antivenom. Thus, this finding highlights the potential use of PANAF-Premium antivenom in treating bites from diverse snakes across sSA and the utility of harnessing the cross-neutralisation potential of antivenoms.

The Royal Armoury: Venomics and antivenomics of king cobra (Ophiophagus hannah) from the Indian Western Ghats.

Despite being famous as 'the king' of the snake world, the king cobra (Ophiophagus hannah) has remained a mysterious species, particularly with respect to its venom ecology. In contrast, venom research has largely focussed on the 'big four' snakes that are greatly responsible for the burden of snakebite in the Indian subcontinent. This study aims to bridge the current void in our understanding of the O. hannah venom by investigating its proteomic, biochemical, pharmacological, and toxinological profiles via interdisciplinary approaches. Considering their physical resemblance, the king cobra is often compared to the spectacled cobra (Naja naja). Comparative venomics of O. hannah and N. naja in this study provided interesting insights into their venom compositions, activities, and potencies. Our findings suggest that the O. hannah venom, despite being relatively less complex than the N. naja venom, is equally potent. Finally, our in vitro and in vivo assays revealed that both Indian polyvalent and Thai Red Cross monovalent antivenoms completely fail to neutralise the O. hannah venom. Our findings provide guidelines for the management of bites from this clinically important yet neglected snake species in India.

Intra-genomic heterogeneity in CpG dinucleotide composition in dengue virus.

PURPOSE: Dengue virus is a life-threatening virus and cases of dengue infection have been increasing steadily in the past decades causing millions of deaths every year. So far, there is no vaccine that works effectively on all serotypes. Recently, CpG-recoded vaccines have proved to be effective against few viruses. METHODS: In this study, evaluation and interpretation of more than 4547 Dengue virus genome sequences were included for analyzing novel CpG dinucleotides rich regions which are shared amid all serotypes. Genomic regions of DENV were synonymously CpG recoded using in silico methods and analyzed for adaptation in both human and Aedes spp. hosts based on CAI scores. RESULTS: The analysis mirrored that serotypes 1, 3, and 4 shared CpG islands present in common regions. DENV-2 CpG islands showed no similarity with any of the CpG islands present in other serotypes. While DENV-3 sequences were found to possess the maximum number of conserved CpG islands stretches; DENV-2 was found to possess the lowest number. We found that all serotypes (with an exception of serotype 2) have CpG island in their 3' UTR. In silico CpG recoding of DENV genomic regions resulted in ∼ 3 fold increase of CpG dinucleotide frequency and comparative analysis based on CAI scores showed decreased adaptive fitness of CpG recoded DENV inside human host. CONCLUSION: These CG-dinucleotide-enriched RNA sequences can be targeted by ZAP (zinc-finger antiviral protein) which can differentiate between host mRNA and viral mRNA. Our in silico findings can further be exploited for CpG-recoding of DENV genomes which can evoke cellular and humoral immune responses by recruiting ZAP-induced RNA degradation machinery and hence providing a promising approach for vaccine development.

Stings on wings: Proteotranscriptomic and biochemical profiling of the lesser banded hornet (Vespa affinis) venom.

Distinct animal lineages have convergently recruited venoms as weaponry for prey capture, anti-predator defence, conspecific competition, or a combination thereof. Most studies, however, have been primarily confined to a narrow taxonomic breadth. The venoms of cone snails, snakes, spiders and scorpions remain particularly well-investigated. Much less explored are the venoms of wasps (Order: Hymenoptera) that are infamous for causing excruciating and throbbing pain, justifying their apex position on Schmidt's pain index, including some that are rated four on four. For example, the lesser banded wasp (V. affinis) is clinically important yet has only been the subject of a few studies, despite being commonly found across tropical and subtropical Asia. Stings from these wasps, especially from multiple individuals of a nest, often lead to clinically severe manifestations, including mastocytosis, myasthenia gravis, optic neuropathy, and life-threatening pathologies such as myocardial infarction and organ failure. However, their venom composition and activity remain unexplored in the Indian subcontinent. Here, we report the proteomic composition, transcriptomic profile, and biochemical and pharmacological activities of V. affinis venom from southern India. Our findings suggest that wasp venoms are rich in diverse toxins that facilitate antipredator defence. Biochemical and pharmacological assessments reveal that these toxins can exhibit significantly higher activities than their homologues in medically important snakes. Their ability to exert potent effects on diverse molecular targets makes them a treasure trove for discovering life-saving therapeutics. Fascinatingly, wasp venoms, being evolutionarily ancient, exhibit a greater degree of compositional and sequence conservation across very distant populations/species, which contrasts with the patterns of venom evolution observed in evolutionarily younger lineages, such as advanced snakes and cone snails.