Toxins isolated from the venom of the brazilian coral snake (Micrurus frontalis frontalis) include hemorrhagic type phospholipases A2 and postsynaptic neurotoxins

Francis, Brian R.; Silva, Nelson Jorge da; Seebart, Corrine; Casais-e-Silva, Luciana Lyra; Schmidt, James J.; Kaiser, Ivan I.

doi:10.1016/s0041-0101(97)00031-7

Cited by 54 publications

(21 citation statements)

References 30 publications

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“…These (and two sequences from M. fulvius and M. tener ) show great sequence similarity to Notechis HT e and to human pancreatic PLA 2 (Figure 13B). Francis et al [196] reported that the hemorrhagic phospholipases from M. frontalis venom lacked phospholipase activity, and now we can explain why. Of the 20 hemorrhagic PLA 2 s reported here, 17 have Tyr50 in the active site instead of Asp50; thus, they cannot bind the Ca 2+ ion required for catalysis.…”

Section: Resultsmentioning

confidence: 73%

“…This extra loop causes them to migrate on SDS-PAGE with apparent molecular weights of 18–23 kDa. From M. frontalis venom, Francis et al [196] isolated basic, 21–23 kDa PLA 2 s that cross-reacted strongly with rabbit polyclonal antibodies raised against the hemorrhagic PLA 2 from Notechis s. scutatus venom, and concluded that most or all of the PLA 2 s in M. frontalis venom are of this type. However, to date, no sequence has been published for any of the M. frontalis hemorrhagic PLA 2 s. Based on the presence of a Helix D-like structure, a probable hemorrhagic phospholipase sequence from venom of M. fulvius was published in 2013, although the authors did not identify it as such [1].…”

Section: Resultsmentioning

confidence: 99%

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Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Aird

Silva

Qiu

et al. 2017

Toxins

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Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A2 (PLA2s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0%) are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%). Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to have arisen in three species by gene duplication and fusion. Four species have transcripts homologous to the nociceptive toxin, (MitTx) α-subunit, but all six species had homologs to the β-subunit. The first non-neurotoxic, non-catalytic elapid phospholipase A2s are reported. All are probably myonecrotic. Phylogenetic analysis indicates that the six taxa diverged 15–35 million years ago and that they split from their last common ancestor with Old World elapines nearly 55 million years ago. Given their early diversification, many cryptic micrurine taxa are anticipated.

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Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Aird

Silva

Qiu

et al. 2017

Toxins

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“…Coral snake envenomations are comparatively infrequent because of their subfossorial behavior and the high incidence of dry bites; nevertheless, the mortality attributed to muscle respiratory paralysis is high (Rengifo and Rodríguez-Acosta, 2004). In spite of being considered amongst the most toxic snakes in America (Roze, 1996), their venom hemostatic activities have been scarcely described since disorders of blood coagulation are not common in human envenomations (Barros et al,1994; Francis et al,1997; Urdaneta et al, 2004; Cecchini et al, 2005; Dokmetjian et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

Hemostatic and toxinological diversities in venom of Micrurus tener tener, Micrurus fulvius fulvius and Micrurus isozonus coral snakes

Salazar

Vivas

Sánchez

et al. 2011

Toxicon

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The coral snake Micrurus tener tener (Mtt) from the Elapidae family inhabits the southwestern United States and produces severe cases of envenomations. Although the majority of Mtt venom components are neurotoxins and phospholipase A2s, this study demonstrated, by SDS-PAGE and molecular exclusion chromatography (MEC), that these venoms also contain high-molecular-weight proteins between 50 and 150 kDa that target the hemostatic system. The biological aspects of other Micrurus venoms were also studied, such as the LD50s of Micrurus isozonus (from 0.52 to 0.61 mg/kg). A pool from these venoms presented a LD50 of 0.57 mg/kg, Micrurus f. fulvius (Mff) and Mtt had LD50s of 0.32 and 0.78 mg/kg, respectively. These venoms contained fibrino(geno)lytic activity, they inhibited platelet aggregation, as well as factor Xa and/or plasmin-like activities. M. isozonus venoms from different Venezuelan geographical regions inhibited ADP-induced platelet aggregation (from 50 to 68%). Micrurus tener tener venom from the United States was the most active with a 95.2% inhibitory effect. This venom showed thrombin-like activity on fibrinogen and human plasma. Fractions of Mtt showed fibrino(geno)lytic activity and inhibition on plasmin amidolytic activity. Several fractions degraded the fibrinogen Aα chains, and fractions F2 and F7 completely degraded both fibrinogen Aα and Bβ chains. To our knowledge, this is the first report on thrombin-like and fibrino(geno)lytic activity and plasmin or factor Xa inhibitors described in Micrurus venoms. Further purification and characterization of these Micrurus venom components could be of therapeutic use in the treatment of hemostatic disorders.

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“…1). Envenomation by these snakes can cause death due to the alpha neurotoxins that cause muscle paralysis and respiratory arrest due to postsynaptic, nondepolarization blockage at the neuromuscular junction by binding competitively to the acetylcholine receptor (Lee, 1970 and1972;Pettigrew and Glass, 1985;Vital-Brazil, 1987;Alape-Giron et al, 1996;Rosso et al, 1996;Francis et al, 1997 ). The current NACSA will no longer be available after October 2008; and therefore, it is important to determine the ability of other coral snake antivenoms to neutralize the toxic effects of the North American coral snake venoms.…”

Section: Introductionmentioning

confidence: 99%

Neutralization of two North American coral snake venoms with United States and Mexican antivenoms

Sánchez

Lopez-Johnston

Rodrı́guez-Acosta

et al. 2008

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Elapid snakes throughout the world are considered very lethal containing neurotoxic venoms that affect the nervous system. When humans are envenomated it is considered a serious medical emergency, and antivenom is the main form of treatment considered, in spite of the fact that some patients may only survive under intensive therapy treatment such as respiratory support. Coral snakes are part of the family Elapidae and envenomations by these snakes are very low (< 2% of total snakebites) in most countries from southeastern United States to Argentina. In the United States there are only two species of coral snakes of medical importance which belong to the Micrurus genera: Micrurus fulvius fulvius (Eastern coral snake) and M. tener tener (Texas coral snake). In 2006, Wyeth pharmaceutical notified customers that the production of the North American Coral Snake Antivenin (NACSA) in the U.S. was discontinued and adequate supplies were available to meet historical needs through the end of October 2008; and therefore, it is of utmost important to consider other antivenoms as alternatives for the treatment of coral snake envenoming. One logical alternative is the coral snake antivenom, Coralmyn, produced by the Mexican company, Bioclon. In order to compare neutralization between NACSA and Coralmyn antivenoms with the North American coral snake venoms, the venom lethal doses (LD 50 ) and antivenom effective doses (ED 50 ) were determined in 18-20 g, female, BALB/c mice. Additionally, venom comparisons were determined through a non reduced SDS-PAGE for M. f. fulvius, M. t. tener and the Mexican coral snake venom, M. nigrocinctus nigrocinctus. Coralmyn antivenom was able to effectively neutralize 3 LD 50 doses of all venom from both M. t. tener and M. f. fulvius, while Wyeth antivenom only neutralized M. f. fulvius venom and was not effective in neutralizing 3 LD 50 doses of M. t. tener venom. Coralmyn is effective in the neutralization of both clinically important coral snake venoms in the U.S.

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Toxins isolated from the venom of the brazilian coral snake (Micrurus frontalis frontalis) include hemorrhagic type phospholipases A2 and postsynaptic neurotoxins

Cited by 54 publications

References 30 publications

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Hemostatic and toxinological diversities in venom of Micrurus tener tener, Micrurus fulvius fulvius and Micrurus isozonus coral snakes

Neutralization of two North American coral snake venoms with United States and Mexican antivenoms

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