Anticoagulant Micrurus venoms: Targets and neutralization

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dc.contributorLaboratório Especial de Coleções Zoológicas (LECZ)pt_BR
dc.contributor.authorDashevsky, Danielpt_BR
dc.contributor.authorBenard-Valle, Melisapt_BR
dc.contributor.authorNeri-Castro, Edgarpt_BR
dc.contributor.authorYoungman, Nicholas J.pt_BR
dc.contributor.authorZdenek, Christina N.pt_BR
dc.contributor.authorAlagón, Alejandropt_BR
dc.contributor.authorPortes Junior, José Antoniopt_BR
dc.contributor.authorFrank, Nathanielpt_BR
dc.contributor.authorFry, Bryan G.pt_BR
dc.identifier.citationDashevsky D, Benard-Valle M, Neri-Castro E, Youngman NJ., Zdenek CN., Alagon A, et al. Anticoagulant Micrurus venoms: targets and neutralization. Toxicol. Lett.. 2020 Nov;in press. doi:10.1016/j.toxlet.2020.11.010.pt_BR
dc.description.abstractSnakebite is a neglected tropical disease with a massive global burden of injury and death. The best current treatments, antivenoms, are plagued by a number of logistical issues that limit supply and access in remote or poor regions. We explore the anticoagulant properties of venoms from the genus Micrurus (coral snakes), which have been largely unstudied, as well as the effectiveness of antivenom and a small-molecule phospholipase inhibitor—varespladib—at counteracting these effects. Our in vitro results suggest that these venoms likely interfere with the formation or function of the prothrombinase complex. We find that the anticoagulant potency varies widely across the genus and is especially pronounced in M. laticollaris. This variation does not appear to correspond to previously described patterns regarding the relative expression of the three-finger toxin and phospholipase A2 (PLA2) toxin families within the venoms of this genus. The coral snake antivenom Coralmyn, is largely unable to ameliorate these effects except for M. ibiboboca. Varespladib on the other hand completely abolished the anticoagulant activity of every venom. This is consistent with the growing body of results showing that varespladib may be an effective treatment for a wide range of toxicity caused by PLA2 toxins from many different snake species. Varespladib is a particularly attractive candidate to help alleviate the burden of snakebite because it is an approved drug that possesses several logistical advantages over antivenom including temperature stability and oral availability.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.relation.ispartofToxicology Letterspt_BR
dc.titleAnticoagulant Micrurus venomspt_BR
dc.contributor.externalUniversity of Queensland (UQ)pt_BR
dc.contributor.externalAustralian National Insect Collection (ANIC)pt_BR
dc.contributor.externalUniversidad Nacional Autónoma de México (UNAM)pt_BR
dc.contributor.externalMToxins Venom Labpt_BR
dc.title.subTargets and neutralizationpt_BR
dc.subject.keywordcoral snakept_BR
dc.subject.keywordelapid coagulotoxicitypt_BR
dc.subject.keywordsnakebite treatmentpt_BR
dc.subject.keywordprothrombinase inhibitionpt_BR
dc.relation.ispartofabbreviatedToxicol. Lett.pt_BR
dc.identifier.citationabntv. 337, p. 91-97, fev. 2021pt_BR
dc.identifier.citationvancouver2021 Feb;337:91-97pt_BR
dc.contributor.butantanPortes Junior, José Antonio|:Aluno|:Laboratório Especial de Coleções Zoológicas (LECZ)pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2018/25749-8pt_BR
dc.sponsorship.butantanAustralian Research Council (ARC)¦¦DP190100304pt_BR
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