Peptide ions were fragmented by CID MS/MS using a normalized collision energy of 35. human victims of snakebites and in the efficacy of antivenoms. snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the (R)-ADX-47273 isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation (R)-ADX-47273 between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites. Author summary is a snake of major medical importance in the Amazon. Its venom is specialized to kill preys in the nature, (R)-ADX-47273 especially because of coagulotoxic and proteolytic activities. envenomings cause local inflammation IgM Isotype Control antibody (PE) and, in a significant proportion, systemic manifestations, namely bleeding disorders. These signs and symptoms are caused by the various toxins present in the venom of this snake, which act in the organism by different mechanisms. It is not known to what extent the composition of the venom that was inoculated by the snake that caused the envenoming can influence the patients clinical condition. To study this subject, this work correlated the constituents of the venom with the medical manifestations of hospitalized individuals, taking advantage of the truth that many individuals bring the snake responsible for the bite. The abundance of each toxin family was related among the venom samples, (R)-ADX-47273 but the variants composition of each toxin was highly variable. Considering the protein families, a group named metalloproteases (SVMP) offered the best correlation with bleeding disorders and edema. Some variants of venom SVMPs, and additional toxin families, such as C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) offered correlation to signs and symptoms presented from the individuals as bleeding disorders, edema, ecchymosis and blister formation. Our results display that venom composition modulates medical manifestations of snakebites. Intro Snakebite is definitely a neglected tropical disease with high incidence in Brazil, especially in the Amazon region [1]. is the snake varieties responsible for approximately 90% of the snakebites in Brazilian Amazon [2]. Unclottable blood, a predictor of systemic bleeding, is the commonest hemostatic disorder in the envenomation, while local signs ranges from pain and swelling at the site of bite moments after the event, to intense signs and symptoms in the bitten limb, with blistering and cells necrosis. Secondary illness, compartmental syndrome, and considerable necrosis can lead to temporary or long term disability of the bitten limb. Spontaneous systemic bleeding and acute renal failure are common complications from envenomings [3,4]. However, the occurrence of each sign/symptom is variable among (R)-ADX-47273 the individuals. In a recent study, 54% of individuals of Manaus, in the Brazilian Amazon, offered unclottable blood at admission [5], while systemic bleeding are reported in around 15% of the instances [6]. Several factors have been associated with the envenomations characteristics and severity, such as the individuals condition, pre-hospital treatments and the time before antivenom therapy [7]. Aspects related to the snake involved in the envenomation, such as their ontogenetic stage, have also been correlated to individuals signs and symptoms, probably caused by the individual variability in snake venom composition [8]. In snakes collected at Brazilian Amazon, venoms are predominately made up by snake venom metalloproteinase (SVMP) followed by C-type lectin-like toxins (CTL), snake venom serine proteinases (SVSP), phospholipases.