02743nas a2200289   4500000000100000008004100001653003900042653002100081653001700102653002000119653002300139100002300162700001900185700001600204700001500220700001900235700001300254700001400267700001500281700001600296245010000312856009900412300001300511490000700524520190800531022001402439       2019                            d10aNeglected tropical diseases (NTDs)10aSnake envenoming10aenvenomation10aNaja annulifera10aSub-Saharan Africa1 aSilva-de-França F1 aVillas-Boas IM1 aSerrano SMT1 aCogliati B1 aChudzinski SAA1 aLopes PH1 aKitano ES1 aOkamoto CK1 aTambourgi D00aNaja annulifera Snake: New insights into the venom components and pathogenesis of envenomation.  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0007017&type=printable  ae00070170 v133 a<p><strong>BACKGROUND: </strong>Naja annulifera is a medically important venomous snake occurring in some of the countries in Sub-Saharan Africa. Accidental bites result in severe coagulation disturbances, systemic inflammation and heart damage, as reported in dogs, and death, by respiratory arrest, in humans. Despite the medical importance of N. annulifera, little is known about its venom composition and the pathogenesis of envenomation. In this paper, the toxic, inflammatory and immunogenic properties of N. annulifera venom were analyzed.</p>

<p><strong>METHODOLOGY/PRINCIPAL FINDINGS: </strong>Venom proteomic analysis identified 79 different proteins, including Three Finger Toxins, Cysteine Rich Secretory Proteins, Metalloproteinases, Phospholipases A2 (PLA2), Hyaluronidase, L-amino-acid oxidase, Cobra Venom Factor and Serine Proteinase. The presence of PLA2, hyaluronidase, fibrinogenolytic and anticoagulant activities was detected using functional assays. The venom was cytotoxic to human keratinocytes. In an experimental murine model of envenomation, it was found that the venom induced local changes, such as swelling, which was controlled by anti-inflammatory drugs. Moreover, the venom caused death, which was preceded by systemic inflammation and pulmonary hemorrhage. The venom was shown to be immunogenic, inducing a strong humoral immune response, with the production of antibodies able to recognize venom components with high molecular weight and to neutralize its lethal activity.</p>

<p><strong>CONCLUSIONS/SIGNIFICANCE: </strong>The results obtained in this study demonstrate that N. annulifera venom contains toxins able to induce local and systemic inflammation, which can contribute to lung damage and death. Moreover, the venom is immunogenic, an important feature that must be considered during the production of a therapeutic anti-N. annulifera antivenom.</p>
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