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The most abundant protein families in viper venoms are Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs) and Phospholipases (PLA2s). These are primarily responsible for the pathophysiology caused by the bite of pit-vipers; however, there are few studies that analyze the pharmacokinetics (PK) of whole venom (WV) and its protein families. We studied the pathophysiology, PK profile and differential absorption of representative toxins from venom of Neotropical Rattlesnake (Crotalus simus) in a large animal model (ovine). Toxins studied included crotoxin (the main lethal component), which causes moderate to severe neurotoxicity; SVSPs, which deplete fibrinogen; and SVMPs, which cause local tissue damage and local and systemic hemorrhage. We found that Whole Venom (WV) was highly bioavailable (86%) 60 h following intramuscular (IM) injection, and extrapolation suggests that bioavailability may be as high as 92%. PK profiles of individual toxins were consistent with their physicochemical properties and expected clinical effects. Lymph cannulated animals absorbed 1.9% of WV through lymph during the first 12 h. Crotoxin was minimally detectable in serum after intravenous (IV) injection; however, following IM injection it was detected in lymph but not in blood. This suggests that crotoxin is quickly released from the blood toward its tissue targets.
Edgar Neri-Castro; Melisa Bénard-Valle; Dayanira Paniagua; Leslie V. Boyer; Lourival D. Possani; Fernando López-Casillas; Alejandro Olvera; Camilo Romero; Fernando Zamudio; Alejandro Alagón. Neotropical Rattlesnake (Crotalus simus) Venom Pharmacokinetics in Lymph and Blood Using an Ovine Model. Toxins 2020, 12, 455 .
AMA StyleEdgar Neri-Castro, Melisa Bénard-Valle, Dayanira Paniagua, Leslie V. Boyer, Lourival D. Possani, Fernando López-Casillas, Alejandro Olvera, Camilo Romero, Fernando Zamudio, Alejandro Alagón. Neotropical Rattlesnake (Crotalus simus) Venom Pharmacokinetics in Lymph and Blood Using an Ovine Model. Toxins. 2020; 12 (7):455.
Chicago/Turabian StyleEdgar Neri-Castro; Melisa Bénard-Valle; Dayanira Paniagua; Leslie V. Boyer; Lourival D. Possani; Fernando López-Casillas; Alejandro Olvera; Camilo Romero; Fernando Zamudio; Alejandro Alagón. 2020. "Neotropical Rattlesnake (Crotalus simus) Venom Pharmacokinetics in Lymph and Blood Using an Ovine Model." Toxins 12, no. 7: 455.
In this communication the isolation, chemical and physiological characterization of three new toxins from the scorpion Centruroides baergi are reported. Their immunoreactive properties with scFvs generated in our group are described. The three new peptides, named Cb1, Cb2 and Cb3 affect voltage-dependent Na+ channels in a differential manner. These characteristics, explain the toxicity of this venom. Molecular interactions in real-time among these toxins and the best recombinant antibodies generated in our group, revealed that one of them was able to neutralize the main toxin of this venom (Cb1). These results represent an important advance for the neutralization of this venom and serve as the basis for generating new scFvs that will allow the neutralization of similar toxins from other venoms that have no yet been neutralized.
Ilse V. Gómez-Ramírez; Lidia Riaño-Umbarila; Timoteo Olamendi-Portugal; Rita Restano-Cassulini; Lourival D. Possani; Baltazar Becerril. Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico. Toxicon 2020, 184, 10 -18.
AMA StyleIlse V. Gómez-Ramírez, Lidia Riaño-Umbarila, Timoteo Olamendi-Portugal, Rita Restano-Cassulini, Lourival D. Possani, Baltazar Becerril. Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico. Toxicon. 2020; 184 ():10-18.
Chicago/Turabian StyleIlse V. Gómez-Ramírez; Lidia Riaño-Umbarila; Timoteo Olamendi-Portugal; Rita Restano-Cassulini; Lourival D. Possani; Baltazar Becerril. 2020. "Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico." Toxicon 184, no. : 10-18.
Centruroides hirsutipalpus (Scorpiones: Buthidae) is related to the “striped scorpion” group inhabiting the western Pacific region of Mexico. Human accidents caused by this species are medically important due to the great number of people stung and the severity of the resulting intoxication. This communication reports an extensive venom characterization using high-throughput proteomic and Illumina transcriptomic sequencing performed with RNA purified from its venom glands. 2,553,529 reads were assembled into 44,579 transcripts. From these transcripts, 23,880 were successfully annoted using Trinotate. Using specialized databases and by performing bioinformatic searches, it was possible to identify 147 putative venom protein transcripts. These include α- and β–type sodium channel toxins (NaScTx), potassium channel toxins (KScTx) (α-, β-, δ-, γ- and λ–types), enzymes (metalloproteases, hyaluronidases, phospholipases, serine proteases, and monooxygenases), protease inhibitors, host defense peptides (HDPs) such as defensins, non-disulfide bridge peptides (NDBPs), anionic peptides, superfamily CAP proteins, insulin growth factor-binding proteins (IGFBPs), orphan peptides, and other venom components (La1 peptides). De novo tandem mass spectrometric sequencing of digested venom identificatied 50 peptides. The venom of C. hirsutipalpus contains the highest reported number (77) of transcripts encoding NaScTxs, which are the components responsible for human fatalities.
Laura L. Valdez-Velázquez; Jimena Cid-Uribe; María Teresa Romero-Gutierrez; Timoteo Olamendi-Portugal; Juana María Jimenez-Vargas; Lourival D. Possani. Transcriptomic and proteomic analyses of the venom and venom glands of Centruroides hirsutipalpus, a dangerous scorpion from Mexico. Toxicon 2020, 179, 21 -32.
AMA StyleLaura L. Valdez-Velázquez, Jimena Cid-Uribe, María Teresa Romero-Gutierrez, Timoteo Olamendi-Portugal, Juana María Jimenez-Vargas, Lourival D. Possani. Transcriptomic and proteomic analyses of the venom and venom glands of Centruroides hirsutipalpus, a dangerous scorpion from Mexico. Toxicon. 2020; 179 ():21-32.
Chicago/Turabian StyleLaura L. Valdez-Velázquez; Jimena Cid-Uribe; María Teresa Romero-Gutierrez; Timoteo Olamendi-Portugal; Juana María Jimenez-Vargas; Lourival D. Possani. 2020. "Transcriptomic and proteomic analyses of the venom and venom glands of Centruroides hirsutipalpus, a dangerous scorpion from Mexico." Toxicon 179, no. : 21-32.
Introduction: A few scorpions are dangerous to humans. Their medical relevance was the initial driving force for venom research. By classical biochemistry and molecular cloning, several venom peptides and their coding transcripts were characterized, mainly those related to toxins. The discovery of other components with novel activities and potential applications has revitalized the interest in the field in the last decade and a half. Non-toxic scorpion species have also attracted major interest. Areas covered: Advances in the identification of scorpion venom components via high-throughput venomics (genomics, transcriptomics and proteomics) up to 2019 are summarized. A classification system for venom-related transcripts and proteins, together with an intuitive systematic nomenclature for RNAseq-generated transcripts are proposed. Venom components classified as Na+, K+, Ca2+, Cl− and TRP channel toxins, enzymes, protease inhibitors, host defense peptides and other peptidic molecules are briefly reviewed, giving a comprehensive picture of the venom. Expert opinion: Modern high-throughput technologies applied to scorpion venom studies have resulted in a dramatic increase in both, the number and diversity of available sequences, leading to a deeper understanding of the composition of scorpion venoms. Still, many newly-discovered venom constituents remain to be characterized, to complete the puzzle of scorpion venoms.
Jimena I. Cid-Uribe; José Ignacio Veytia-Bucheli; Teresa Romero-Gutierrez; Ernesto Ortiz; Lourival D. Possani. Scorpion venomics: a 2019 overview. Expert Review of Proteomics 2019, 17, 67 -83.
AMA StyleJimena I. Cid-Uribe, José Ignacio Veytia-Bucheli, Teresa Romero-Gutierrez, Ernesto Ortiz, Lourival D. Possani. Scorpion venomics: a 2019 overview. Expert Review of Proteomics. 2019; 17 (1):67-83.
Chicago/Turabian StyleJimena I. Cid-Uribe; José Ignacio Veytia-Bucheli; Teresa Romero-Gutierrez; Ernesto Ortiz; Lourival D. Possani. 2019. "Scorpion venomics: a 2019 overview." Expert Review of Proteomics 17, no. 1: 67-83.
Every year in Mexico, around 300,000 people suffer from accidents related to scorpion stings. Among the scorpion species dangerous to human is Centruroides ornatus, whose venom characterization is described here. From this venom, a total of 114 components were found using chromatographic separation and mass spectrometry analysis. The most abundant ones have molecular masses between 3000-4000 Da and 6000–8000 Da respectively, similar to other known K+ and Na+-channel specific scorpion peptides. Using intraperitoneal injections into CD1 mice, we were able to identify and fully sequenced three new lethal toxins. We propose to name them Co1, Co2 and Co3 toxins, which correspond to toxins 1 to 3 of the abbreviated species name (Co). Electrophysiology analysis of these peptides using heterologously expressed human Na+-channels revealed a typical β-toxin effect. Peptide Co52 (the most abundant peptide in the venom) showed no activity in our in vivo and in vitro model assays. A phylogenetic analysis groups the Co1, Co2 and Co3 among other β-toxins from Centruroides scorpions. Peptide Co52 segregates among peptides of unknown defined functions.
I.A. García-Guerrero; E. Cárcamo-Noriega; F. Gómez-Lagunas; E. González-Santillán; F.Z. Zamudio; G.B. Gurrola; L.D. Possani. Biochemical characterization of the venom from the Mexican scorpion Centruroides ornatus, a dangerous species to humans. Toxicon 2019, 173, 27 -38.
AMA StyleI.A. García-Guerrero, E. Cárcamo-Noriega, F. Gómez-Lagunas, E. González-Santillán, F.Z. Zamudio, G.B. Gurrola, L.D. Possani. Biochemical characterization of the venom from the Mexican scorpion Centruroides ornatus, a dangerous species to humans. Toxicon. 2019; 173 ():27-38.
Chicago/Turabian StyleI.A. García-Guerrero; E. Cárcamo-Noriega; F. Gómez-Lagunas; E. González-Santillán; F.Z. Zamudio; G.B. Gurrola; L.D. Possani. 2019. "Biochemical characterization of the venom from the Mexican scorpion Centruroides ornatus, a dangerous species to humans." Toxicon 173, no. : 27-38.
Scorpion toxins are thought to have originated from ancestral housekeeping genes that underwent diversification and neofunctionalization, as a result of positive selection. Our understanding of the evolutionary origin of these peptides is hindered by the patchiness of existing taxonomic sampling. While recent studies have shown phylogenetic inertia in some scorpion toxins at higher systematic levels, evolutionary dynamics of toxins among closely related taxa remain unexplored. In this study, we used new and previously published transcriptomic resources to assess evolutionary relationships of closely related scorpions from the family Hadruridae and their toxins. In addition, we surveyed the incidence of scorpine-like peptides (SLP, a type of potassium channel toxin), which were previously known from 21 scorpion species. We demonstrate that scorpine-like peptides exhibit gene duplications. Our molecular analyses demonstrate that only eight sites of two SLP copies found in scorpions are evolving under positive selection, with more sites evolving under negative selection, in contrast to previous findings. These results show evolutionary conservation in toxin diversity at shallow taxonomic scale.
Carlos E. Santibáñez-López; Matthew R. Graham; Prashant P. Sharma; Ernesto Ortiz; Lourival D. Possani. Hadrurid Scorpion Toxins: Evolutionary Conservation and Selective Pressures. Toxins 2019, 11, 637 .
AMA StyleCarlos E. Santibáñez-López, Matthew R. Graham, Prashant P. Sharma, Ernesto Ortiz, Lourival D. Possani. Hadrurid Scorpion Toxins: Evolutionary Conservation and Selective Pressures. Toxins. 2019; 11 (11):637.
Chicago/Turabian StyleCarlos E. Santibáñez-López; Matthew R. Graham; Prashant P. Sharma; Ernesto Ortiz; Lourival D. Possani. 2019. "Hadrurid Scorpion Toxins: Evolutionary Conservation and Selective Pressures." Toxins 11, no. 11: 637.
The soluble venom of the scorpion Tityus macrochirus was separated by chromatographic procedures and three homogeneous peptides were obtained and their primary structures were determined. They were called: Tma1-Tma3, from the abbreviated name of the scorpion. Tma1 is a peptide containing 65 amino acids with four disulfide linkages and a molecular weight of 7386.2 Da. It is a mammalian toxin, shown to affect human sodium-channels sub-types hNav1.6 and hNav1.4. Tma2 and Tma3 are peptides containing 69 amino acids linked by four disulfide bonds, molecular weights 7819.7 and 7830.0 Da, respectively. They do not affect human sodium-channels but are lethal to insects (crickets). A phylogenic analysis of the three peptides and those of other toxic peptides isolated from the genus Tityus and Centruroides were grouped together and analyzed, permitting to obtain a topology with two main clades, one includes most sodium-channel anti-insect scorpion toxins and others includes mostly sodium-channel scorpion toxins anti-mammalian. Tma1 segregates among a group of well-studied β-class toxins of other Tityus species such as T. discrepans, T. obscurus and T. pachyurus. Tma2 and Tma3 are associated with anti-insect toxins, particularly with one of T. obscurus. This phylogenetic analysis confirms and enforces our experimental results obtained with these three new sodium-channel scorpion toxins.
Clara Andrea Rincón Cortes; Timoteo Olamendi-Portugal; Edson Norberto Carcamo-Noriega; Edmundo González Santillán; Fernando Zamudio Zuñiga; Edgar Antonio Reyes-Montaño; Nohora Angélica Vega Castro; Lourival Domingos Possani. Structural and functional characterization of toxic peptides purified from the venom of the Colombian scorpion Tityus macrochirus. Toxicon 2019, 169, 5 -11.
AMA StyleClara Andrea Rincón Cortes, Timoteo Olamendi-Portugal, Edson Norberto Carcamo-Noriega, Edmundo González Santillán, Fernando Zamudio Zuñiga, Edgar Antonio Reyes-Montaño, Nohora Angélica Vega Castro, Lourival Domingos Possani. Structural and functional characterization of toxic peptides purified from the venom of the Colombian scorpion Tityus macrochirus. Toxicon. 2019; 169 ():5-11.
Chicago/Turabian StyleClara Andrea Rincón Cortes; Timoteo Olamendi-Portugal; Edson Norberto Carcamo-Noriega; Edmundo González Santillán; Fernando Zamudio Zuñiga; Edgar Antonio Reyes-Montaño; Nohora Angélica Vega Castro; Lourival Domingos Possani. 2019. "Structural and functional characterization of toxic peptides purified from the venom of the Colombian scorpion Tityus macrochirus." Toxicon 169, no. : 5-11.
Many peptides in scorpion venoms are amidated at their C-termini. This post-translational modification is paramount for the correct biological function of ion channel toxins and antimicrobial peptides, among others. The discovery of canonical amidation sequences in transcriptome-derived scorpion proproteins suggests that a conserved enzymatic α-amidation system must be responsible for this modification of scorpion peptides. A transcriptomic approach was employed to identify sequences putatively encoding enzymes of the α-amidation pathway. A dual enzymatic α-amidation system was found, consisting of the membrane-anchored, bifunctional, peptidylglycine α-amidating monooxygenase (PAM) and its paralogs, soluble monofunctional peptidylglycine α-hydroxylating monooxygenase (PHMm) and peptidyl-α-hydroxyglycine α-amidating lyase (PALm). Independent genes encode these three enzymes. Amino acid residues responsible for ion coordination and enzymatic activity are conserved in these sequences, suggesting that the enzymes are functional. Potential endoproteolytic recognition sites for proprotein convertases in the PAM sequence indicate that PAM-derived soluble isoforms may also be expressed. Sequences potentially encoding proprotein convertases (PC1 and PC2), carboxypeptidase E (CPE), and other enzymes of the α-amidation pathway, were also found, confirming the presence of this pathway in scorpions.
Gustavo Delgado-Prudencio; Lourival D. Possani; Baltazar Becerril; Ernesto Ortiz. The Dual α-Amidation System in Scorpion Venom Glands. Toxins 2019, 11, 425 .
AMA StyleGustavo Delgado-Prudencio, Lourival D. Possani, Baltazar Becerril, Ernesto Ortiz. The Dual α-Amidation System in Scorpion Venom Glands. Toxins. 2019; 11 (7):425.
Chicago/Turabian StyleGustavo Delgado-Prudencio; Lourival D. Possani; Baltazar Becerril; Ernesto Ortiz. 2019. "The Dual α-Amidation System in Scorpion Venom Glands." Toxins 11, no. 7: 425.
Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing more therapeutic antiviral compounds. Hepatitis C virus (HCV) and dengue virus (DENV) belong to the Flaviviridae family and are an increasing global health threat. Our previous study reported that the crude venom of Scorpio maurus palmatus possessed anti-HCV and anti-DENV activities in vitro. We report here the characterization of a natural antiviral peptide (scorpion-like peptide Smp76) that prevents HCV and DENV infection. Smp76 was purified from S. m. palmatus venom and contains 76 amino acids with six residues of cysteine. Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). A potential antiviral activity of Smp76 was detected in culture cells with an approximate IC50 of 0.01 μg/ml. Moreover, Smp76 prevents HCV infection and suppresses secondary infection, by inactivating extra-cellular infectious particles without affecting viral replication. Interestingly, Smp76 is neither toxic nor hemolytic in vitro at a concentration 1000-fold higher than that required for antiviral activity. Conclusively, this report highlights novel anti-HCV and anti-DENV activities of Smp76, which may lay the foundation for developing a new therapeutic intervention against these flaviviruses.
Alaa M. H. El-Bitar; Moustafa Sarhan; Mohamed A. Abdel-Rahman; Veronica Quintero-Hernandez; Chie Aoki-Utsubo; Mohsen A. Moustafa; Lourival D. Possani; Hak Hotta. Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus. International Journal of Peptide Research and Therapeutics 2019, 26, 811 -821.
AMA StyleAlaa M. H. El-Bitar, Moustafa Sarhan, Mohamed A. Abdel-Rahman, Veronica Quintero-Hernandez, Chie Aoki-Utsubo, Mohsen A. Moustafa, Lourival D. Possani, Hak Hotta. Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus. International Journal of Peptide Research and Therapeutics. 2019; 26 (2):811-821.
Chicago/Turabian StyleAlaa M. H. El-Bitar; Moustafa Sarhan; Mohamed A. Abdel-Rahman; Veronica Quintero-Hernandez; Chie Aoki-Utsubo; Mohsen A. Moustafa; Lourival D. Possani; Hak Hotta. 2019. "Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus." International Journal of Peptide Research and Therapeutics 26, no. 2: 811-821.
A peptide (Cn29) from the venom of the scorpion Centruroides noxius (about 2% of the soluble venom) was purified and its primary and three-dimensional structures were determined. The peptide contains 27 amino acids with primary sequence: LCLSCRGGDYDCRVKGTCENGKCVCGS. The peptide is tightly packed by three disulfide linkages formed between C2-C23, C5-C18 and C12-C25. Since the native peptide was obtained in limited amounts, the full synthetic peptide was prepared using the standard F-moc-based solid phase synthesis method of Merrifield. The native and synthetic peptides were shown to be identical by sequencing, HPLC separation and mass spectrometry. The solution structure of the peptide solved from NMR data shows that it consists of a well-defined N-terminal region without regular secondary structure extending from Leu 1 to Asp 9, followed by a short helical fragment from Tyr10 to Val14 and two short β strands (Thr17-Glu19 and Lys22-Val24). The primary and tertiary structures of Cn29 are different from all other scorpion peptides described in the literature. Transcriptome analysis of RNA obtained from C. noxius confirmed the expression of a gene coding for Cn29 in its venom gland. Initial experiments were conducted to identify its possible function: lethality tests in mice and insects as well as ion-channel binding using in vitro electrophysiological assays. None of the physiological or biological tests displayed any activity for this peptide, which at present is considered to be another orphan peptide found in scorpion venoms. The peptide is thus the first example of a novel structural component present in scorpion venoms.
G.B. Gurrola; J.I. Guijarro; M. Delepierre; R.L.L. Mendoza; J.I. Cid-Uribe; F.V. Coronas; L.D. Possani. Cn29, a novel orphan peptide found in the venom of the scorpion Centruroides noxius: Structure and function. Toxicon 2019, 167, 184 -191.
AMA StyleG.B. Gurrola, J.I. Guijarro, M. Delepierre, R.L.L. Mendoza, J.I. Cid-Uribe, F.V. Coronas, L.D. Possani. Cn29, a novel orphan peptide found in the venom of the scorpion Centruroides noxius: Structure and function. Toxicon. 2019; 167 ():184-191.
Chicago/Turabian StyleG.B. Gurrola; J.I. Guijarro; M. Delepierre; R.L.L. Mendoza; J.I. Cid-Uribe; F.V. Coronas; L.D. Possani. 2019. "Cn29, a novel orphan peptide found in the venom of the scorpion Centruroides noxius: Structure and function." Toxicon 167, no. : 184-191.
Two 1,4-benzoquinone derivatives, found in the venom of the scorpionDiplocentrus melicifollowing exposure to air, have been isolated, characterized, synthesized, and assessed for antimicrobial activities. Initially a white, viscous liquid, the extracted venom colors within minutes under ambient conditions. From this colored mixture, two compounds, one red, the other blue, were isolated and purified using chromatography. After a variety of NMR and mass spectrometry experiments, the red compound was determined to be 3,5- dimethoxy-2-(methylthio)cyclohexa-2,5-diene-1,4-dione, and the blue compound was determined to be 5-methoxy-2,3- bis(methylthio)cyclohexa-2,5-diene-1,4-dione. Because extremely small amounts of these compounds were isolated from the scorpion venom, we developed laboratory syntheses from commercially available precursors, allowing us to produce sufficient quantities for crystallization and biological assays. The red benzoquinone is effective againstStaphylococcus aureus[minimum inhibitory concentration (MIC) = 4 µg/mL], while the blue benzoquinone is active againstMycobacterium tuberculosis(MIC = 4 µg/mL) and even against a multidrug-resistant (MDR) strain with nearly equal effectiveness. The bactericidal effects of both benzoquinones show comparable activity to commercially available antibiotics used against these pathogens and were cytotoxic to neoplastic cell lines, suggesting their potential as lead compounds for the development of novel antimicrobial and anticancer drugs. Importantly, the blue benzoquinone was also effective in vivo with mouse models of MDR tuberculosis infection. After treatment for 2 mo, four mice with late-stage active MDR tuberculosis had a significant decrease in pulmonary bacillary loads and tissue damage. Healthy mice served as negative controls and tolerated treatment well, without adverse side effects.
Edson Norberto Carcamo-Noriega; Shyam Sathyamoorthi; Shibdas Banerjee; Elumalai Gnanamani; Monserrat Mendoza Trujillo; Dulce Mata-Espinosa; Rogelio Hernández-Pando; José Ignacio Veytia-Bucheli; Lourival D. Possani; Richard N. Zare. 1,4-Benzoquinone antimicrobial agents againstStaphylococcus aureusandMycobacterium tuberculosisderived from scorpion venom. Proceedings of the National Academy of Sciences 2019, 116, 12642 -12647.
AMA StyleEdson Norberto Carcamo-Noriega, Shyam Sathyamoorthi, Shibdas Banerjee, Elumalai Gnanamani, Monserrat Mendoza Trujillo, Dulce Mata-Espinosa, Rogelio Hernández-Pando, José Ignacio Veytia-Bucheli, Lourival D. Possani, Richard N. Zare. 1,4-Benzoquinone antimicrobial agents againstStaphylococcus aureusandMycobacterium tuberculosisderived from scorpion venom. Proceedings of the National Academy of Sciences. 2019; 116 (26):12642-12647.
Chicago/Turabian StyleEdson Norberto Carcamo-Noriega; Shyam Sathyamoorthi; Shibdas Banerjee; Elumalai Gnanamani; Monserrat Mendoza Trujillo; Dulce Mata-Espinosa; Rogelio Hernández-Pando; José Ignacio Veytia-Bucheli; Lourival D. Possani; Richard N. Zare. 2019. "1,4-Benzoquinone antimicrobial agents againstStaphylococcus aureusandMycobacterium tuberculosisderived from scorpion venom." Proceedings of the National Academy of Sciences 116, no. 26: 12642-12647.
Venom glands and soluble venom from the Mexican scorpion Centruroides limpidus (Karsch, 1879) were used for transcriptomic and proteomic analyses, respectively. An RNA-seq was performed by high-throughput sequencing with the Illumina platform. Approximately 80 million reads were obtained and assembled into 198,662 putative transcripts, of which 11,058 were annotated by similarity to sequences from available databases. A total of 192 venom-related sequences were identified, including Na+ and K+ channel-acting toxins, enzymes, host defense peptides, and other venom components. The most diverse transcripts were those potentially coding for ion channel-acting toxins, mainly those active on Na+ channels (NaScTx). Sequences corresponding to β- scorpion toxins active of K+ channels (KScTx) and λ-KScTx are here reported for the first time for a scorpion of the genus Centruroides. Mass fingerprint corroborated that NaScTx are the most abundant components in this venom. Liquid chromatography coupled to mass spectometry (LC-MS/MS) allowed the identification of 46 peptides matching sequences encoded in the transcriptome, confirming their expression in the venom. This study corroborates that, in the venom of toxic buthid scorpions, the more abundant and diverse components are ion channel-acting toxins, mainly NaScTx, while they lack the HDP diversity previously demonstrated for the non-buthid scorpions. The highly abundant and diverse antareases explain the pancreatitis observed after envenomation by this species.
Jimena I. Cid-Uribe; Erika P. Meneses; Cesar V. F. Batista; Ernesto Ortiz; Lourival D. Possani. Dissecting Toxicity: The Venom Gland Transcriptome and the Venom Proteome of the Highly Venomous Scorpion Centruroides limpidus (Karsch, 1879). Toxins 2019, 11, 247 .
AMA StyleJimena I. Cid-Uribe, Erika P. Meneses, Cesar V. F. Batista, Ernesto Ortiz, Lourival D. Possani. Dissecting Toxicity: The Venom Gland Transcriptome and the Venom Proteome of the Highly Venomous Scorpion Centruroides limpidus (Karsch, 1879). Toxins. 2019; 11 (5):247.
Chicago/Turabian StyleJimena I. Cid-Uribe; Erika P. Meneses; Cesar V. F. Batista; Ernesto Ortiz; Lourival D. Possani. 2019. "Dissecting Toxicity: The Venom Gland Transcriptome and the Venom Proteome of the Highly Venomous Scorpion Centruroides limpidus (Karsch, 1879)." Toxins 11, no. 5: 247.
Californiconus californicus, previously named Conus californicus, has always been considered a unique species within cone snails, because of its molecular, toxicological and morphological singularities; including the wide range of its diet, since it is capable of preying indifferently on fish, snails, octopus, shrimps, and worms. We report here a new cysteine pattern conotoxin assigned to the O1-superfamily capable of inhibiting the growth of Mycobacterium tuberculosis (Mtb). The conotoxin was tested on a pathogen reference strain (H37Rv) and multidrug-resistant strains, having an inhibition effect on growth with a minimal inhibitory concentration (MIC) range of 3.52–0.22 μM, similar concentrations to drugs used in clinics. The peptide was purified from the venom using reverse phase high-performance liquid chromatography (RP-HPLC), a partial sequence was constructed by Edman degradation, completed by RACE and confirmed with venom gland transcriptome. The 32-mer peptide containing eight cysteine residues was named O1_cal29b, according to the current nomenclature for this type of molecule. Moreover, transcriptomic analysis of O-superfamily toxins present in the venom gland of the snail allowed us to assign several signal peptides to O2 and O3 superfamilies not described before in C. californicus, with new conotoxins frameworks.
Johanna Bernáldez-Sarabia; Andrea Figueroa-Montiel; Salvador Dueñas; Karla Cervantes-Luévano; Jesús A. Beltrán; Ernesto Ortiz; Samanta Jiménez; Lourival D. Possani; Jorge F. Paniagua-Solís; Jorge Gonzalez-Canudas; Alexei Licea-Navarro. The Diversified O-Superfamily in Californiconus californicus Presents a Conotoxin with Antimycobacterial Activity. Toxins 2019, 11, 128 .
AMA StyleJohanna Bernáldez-Sarabia, Andrea Figueroa-Montiel, Salvador Dueñas, Karla Cervantes-Luévano, Jesús A. Beltrán, Ernesto Ortiz, Samanta Jiménez, Lourival D. Possani, Jorge F. Paniagua-Solís, Jorge Gonzalez-Canudas, Alexei Licea-Navarro. The Diversified O-Superfamily in Californiconus californicus Presents a Conotoxin with Antimycobacterial Activity. Toxins. 2019; 11 (2):128.
Chicago/Turabian StyleJohanna Bernáldez-Sarabia; Andrea Figueroa-Montiel; Salvador Dueñas; Karla Cervantes-Luévano; Jesús A. Beltrán; Ernesto Ortiz; Samanta Jiménez; Lourival D. Possani; Jorge F. Paniagua-Solís; Jorge Gonzalez-Canudas; Alexei Licea-Navarro. 2019. "The Diversified O-Superfamily in Californiconus californicus Presents a Conotoxin with Antimycobacterial Activity." Toxins 11, no. 2: 128.
The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen. This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions. This single antibody fragment showed the properties of a polyvalent antivenom. These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization.
Lidia Riaño-Umbarila; Ilse V. Gómez-Ramírez; Luis M. Ledezma-Candanoza; Timoteo Olamendi-Portugal; Everardo Remi Rodríguez-Rodríguez; Guillermo Fernández-Taboada; Lourival D. Possani; Baltazar Becerril. Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms. Toxins 2019, 11, 32 .
AMA StyleLidia Riaño-Umbarila, Ilse V. Gómez-Ramírez, Luis M. Ledezma-Candanoza, Timoteo Olamendi-Portugal, Everardo Remi Rodríguez-Rodríguez, Guillermo Fernández-Taboada, Lourival D. Possani, Baltazar Becerril. Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms. Toxins. 2019; 11 (1):32.
Chicago/Turabian StyleLidia Riaño-Umbarila; Ilse V. Gómez-Ramírez; Luis M. Ledezma-Candanoza; Timoteo Olamendi-Portugal; Everardo Remi Rodríguez-Rodríguez; Guillermo Fernández-Taboada; Lourival D. Possani; Baltazar Becerril. 2019. "Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms." Toxins 11, no. 1: 32.
The scorpion venom is a cocktail of many components. Its composition can exhibit a level of plasticity in response to different behavioral and environmental factors, leading to intraspecific variation. The toxicity and specificity of scorpion venoms appear to be taxon-dependent, due to a co-evolutionary interaction with prey and predators, which shaped the composition at the molecular level. The venom regeneration by the venom glands is an asynchronous process, in which particular components are expressed at different stages and at different rates. According to this, it can be reasonably assumed that the regeneration of toxicity in the venom is also asynchronous. In this work, we studied the toxicity regeneration dynamics by the scorpion Centruroides limpidus after full venom depletion by electrical stimulation. For this, we evaluated the toxicity of venom samples extracted at different days post depletion, against insects (crickets) and mammals (humans, by assessing the venom activity on the human voltage-dependent Na+ channel Nav1.6). The regeneration of toxicity against humans lagged behind that against crickets (13 vs 10 days, respectively). Thirteen days after depletion the venom seems to be replenished. Our results show asynchrony in the regeneration of species-specific toxic activity in the venom of Centruroides limpidus. The understanding of the venom regeneration kinetics for the different scorpion species will help to design venom extraction protocols that could maximize the yield and quality of the collected venoms.
Edson Norberto Carcamo-Noriega; Lourival Domingos Possani; Ernesto Ortiz. Venom content and toxicity regeneration after venom gland depletion by electrostimulation in the scorpion Centruroides limpidus. Toxicon 2018, 157, 87 -92.
AMA StyleEdson Norberto Carcamo-Noriega, Lourival Domingos Possani, Ernesto Ortiz. Venom content and toxicity regeneration after venom gland depletion by electrostimulation in the scorpion Centruroides limpidus. Toxicon. 2018; 157 ():87-92.
Chicago/Turabian StyleEdson Norberto Carcamo-Noriega; Lourival Domingos Possani; Ernesto Ortiz. 2018. "Venom content and toxicity regeneration after venom gland depletion by electrostimulation in the scorpion Centruroides limpidus." Toxicon 157, no. : 87-92.
To understand the diversity of scorpion venom, RNA from venomous glands from a sawfinger scorpion, Serradigitus gertschi, of the family Vaejovidae, was extracted and used for transcriptomic analysis. A total of 84,835 transcripts were assembled after Illumina sequencing. From those, 119 transcripts were annotated and found to putatively code for peptides or proteins that share sequence similarities with the previously reported venom components of other species. In accordance with sequence similarity, the transcripts were classified as potentially coding for 37 ion channel toxins; 17 host defense peptides; 28 enzymes, including phospholipases, hyaluronidases, metalloproteases, and serine proteases; nine protease inhibitor-like peptides; 10 peptides of the cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 protein superfamily; seven La1-like peptides; and 11 sequences classified as “other venom components”. A mass fingerprint performed by mass spectrometry identified 204 components with molecular masses varying from 444.26 Da to 12,432.80 Da, plus several higher molecular weight proteins whose precise masses were not determined. The LC-MS/MS analysis of a tryptic digestion of the soluble venom resulted in the de novo determination of 16,840 peptide sequences, 24 of which matched sequences predicted from the translated transcriptome. The database presented here increases our general knowledge of the biodiversity of venom components from neglected non-buthid scorpions.
Maria Teresa Romero-Gutiérrez; Carlos Eduardo Santibáñez-López; Juana María Jiménez-Vargas; Cesar Vicente Ferreira Batista; Ernesto Ortiz; Lourival Domingos Possani. Transcriptomic and Proteomic Analyses Reveal the Diversity of Venom Components from the Vaejovid Scorpion Serradigitus gertschi. Toxins 2018, 10, 359 .
AMA StyleMaria Teresa Romero-Gutiérrez, Carlos Eduardo Santibáñez-López, Juana María Jiménez-Vargas, Cesar Vicente Ferreira Batista, Ernesto Ortiz, Lourival Domingos Possani. Transcriptomic and Proteomic Analyses Reveal the Diversity of Venom Components from the Vaejovid Scorpion Serradigitus gertschi. Toxins. 2018; 10 (9):359.
Chicago/Turabian StyleMaria Teresa Romero-Gutiérrez; Carlos Eduardo Santibáñez-López; Juana María Jiménez-Vargas; Cesar Vicente Ferreira Batista; Ernesto Ortiz; Lourival Domingos Possani. 2018. "Transcriptomic and Proteomic Analyses Reveal the Diversity of Venom Components from the Vaejovid Scorpion Serradigitus gertschi." Toxins 10, no. 9: 359.
The recent publication of high-throughput transcriptomic and proteomic analyses of scorpion venom glands has increased our knowledge on the biodiversity of venom components. In this contribution, we report the transcriptome of the venom gland and the proteome of the venom for the scorpion species Paravaejovis schwenkmeyeri, a member of the family Vaejovidae. We report 138 annotated transcripts encoding putative peptides/proteins with sequence identity to known venom components available from different databases. A fingerprint analysis containing the molecular masses of 212 components of the whole soluble venom revealed molecular weights of approximately 700 to 13,800 Da, with most detected proteins ranging from 1500 to 3000 Da. Amino acid sequencing of venom components by LC-MS/MS allowed the identification of fragments from 27 peptides encoded by transcripts found in the transcriptome analysis. Enzymatic assays conducted with the soluble venom fraction confirmed the presence of enzymes such as hyaluronidases and phospholipases. The database presented here increases our general knowledge on the biodiversity of venom components from neglected non-buthid scorpions.
Jimena I. Cid-Uribe; Carlos E. Santibáñez-López; Erika P. Meneses; Cesar Batista; Juana M. Jiménez-Vargas; Ernesto Ortiz; Lourival D. Possani. The diversity of venom components of the scorpion species Paravaejovis schwenkmeyeri (Scorpiones: Vaejovidae) revealed by transcriptome and proteome analyses. Toxicon 2018, 151, 47 -62.
AMA StyleJimena I. Cid-Uribe, Carlos E. Santibáñez-López, Erika P. Meneses, Cesar Batista, Juana M. Jiménez-Vargas, Ernesto Ortiz, Lourival D. Possani. The diversity of venom components of the scorpion species Paravaejovis schwenkmeyeri (Scorpiones: Vaejovidae) revealed by transcriptome and proteome analyses. Toxicon. 2018; 151 ():47-62.
Chicago/Turabian StyleJimena I. Cid-Uribe; Carlos E. Santibáñez-López; Erika P. Meneses; Cesar Batista; Juana M. Jiménez-Vargas; Ernesto Ortiz; Lourival D. Possani. 2018. "The diversity of venom components of the scorpion species Paravaejovis schwenkmeyeri (Scorpiones: Vaejovidae) revealed by transcriptome and proteome analyses." Toxicon 151, no. : 47-62.
A proteomic analysis of the soluble venom of the coral snake Micrurus pyrrhocryptus is reported in this work. The whole soluble venom was separated by RP-HPLC and the molecular weights of its components (over 100) were determined by mass spectrometry. Three main sets of components were identified, corresponding to peptides with molecular masses from 5 to 8 kDa, proteins from 12 to 16 kDa and proteins from 20 to 30 kDa. Two components were fully sequenced: one α-neurotoxic peptide of 7210 Da with slight blocking activity of the nicotinic acetylcholine receptor (nAChR) and a phospholipase A2 (PLA2) with molecular weight 13517 Da and no effect on the nAChR. PLA2 activity was evaluated for all RP-HPLC components. In addition, N-terminal sequence was obtained for eleven components using Edman degradation. Among these, three were similar to known PLA2's, six to three-finger toxins (3FTx) and one to Kunitz-type serine protease inhibitors. Two-dimensional gel electrophoresis of the venom allowed the separation of about thirty spots with components of molecular weights from 25 to 70 kDa. Seventeen spots were recovered from the gel, digested with trypsin and the corresponding peptides (85) were sequenced by MS/MS allowing identification of amino acid sequences with similarities to snake venom metalloproteases (SVMP), PLA2's, L-amino acid oxidases (LAAO), acetylcholinesterases (AChE) and serine proteases (SP). In addition, LC-MS analysis of peptides obtained from tryptic digestion of whole soluble venom allowed the identification of 695 peptides, whose amino acid sequence could correspond to at least 355 components found in other snake venoms, where C-type lectins, vespryns, zinc finger proteins, and waprins were found, among others. These results show the complexity of the venom and provide important knowledge for future work on identification and activity determination of venom components from this coral snake.
Timoteo Olamendi-Portugal; César V.F. Batista; Martha Pedraza-Escalona; Rita Restano-Cassulini; Fernando Z. Zamudio; Melisa Benard-Valle; Adolfo Rafael de Roodt; Lourival D. Possani. New insights into the proteomic characterization of the coral snake Micrurus pyrrhocryptus venom. Toxicon 2018, 153, 23 -31.
AMA StyleTimoteo Olamendi-Portugal, César V.F. Batista, Martha Pedraza-Escalona, Rita Restano-Cassulini, Fernando Z. Zamudio, Melisa Benard-Valle, Adolfo Rafael de Roodt, Lourival D. Possani. New insights into the proteomic characterization of the coral snake Micrurus pyrrhocryptus venom. Toxicon. 2018; 153 ():23-31.
Chicago/Turabian StyleTimoteo Olamendi-Portugal; César V.F. Batista; Martha Pedraza-Escalona; Rita Restano-Cassulini; Fernando Z. Zamudio; Melisa Benard-Valle; Adolfo Rafael de Roodt; Lourival D. Possani. 2018. "New insights into the proteomic characterization of the coral snake Micrurus pyrrhocryptus venom." Toxicon 153, no. : 23-31.
In T cells, the Kv1.3 and the KCa3.1 potassium channels regulate the membrane potential and calcium homeostasis. Notably, during TEM cell activation, the number of Kv1.3 channels on the cell membrane dramatically increases. Kv1.3 blockade results in inhibition of Ca2+ signaling in TEM cells, thus eliciting an immunomodulatory effect. Among the naturally occurring peptides, the Vm24 toxin from the Mexican scorpion Vaejovis mexicanus is the most potent and selective Kv1.3 channel blocker known, which makes it a promissory candidate for its use in the clinic. We have shown that addition of Vm24 to TCR-activated human T cells inhibits CD25 expression, cell proliferation and reduces delayed-type hypersensitivity reactions in a chronic inflammation model. Here, we used the Vm24 toxin as a tool to investigate the molecular events that follow Kv1.3 blockade specifically on human CD4+ TEM cells as they are actively involved in inflammation and are key mediators of autoimmune diseases. We combined cell viability, activation, and multiplex cytokine assays with a proteomic analysis to identify the biological processes affected by Kv1.3 blockade on healthy donors CD4+ TEM cells, following TCR activation in the presence or absence of the Vm24 toxin. The peptide completely blocked Kv1.3 channels currents without impairing TEM cell viability, and in response to TCR stimulation, it inhibited the expression of the activation markers CD25 and CD40L (but not that of CD69), as well as the secretion of the pro-inflammatory cytokines IFN-γ and TNF and the anti-inflammatory cytokines IL-4, IL-5, IL-9, IL-10, and IL-13. These results, in combination with data from the proteomic analysis, indicate that the biological processes most affected by the blockade of Kv1.3 channels in a T cell activation context were cytokine-cytokine receptor interaction, mRNA processing via spliceosome, response to unfolded proteins and intracellular vesicle transport, targeting the cell protein synthesis machinery. The Vm24 toxin, a highly specific inhibitor of Kv1.3 channels allowed us to define downstream functions of the Kv1.3 channels in human CD4+ TEM lymphocytes. Blocking Kv1.3 channels profoundly affects the mRNA synthesis machinery, the unfolded protein response and the intracellular vesicle transport, impairing the synthesis and secretion of cytokines in response to TCR engagement, underscoring the role of Kv1.3 channels in regulating TEM lymphocyte function.
José Ignacio Veytia-Bucheli; Juana María Jiménez-Vargas; Erika Isabel Melchy-Pérez; Monserrat Alba Sandoval-Hernández; Lourival Domingos Possani; Yvonne Rosenstein. Kv1.3 channel blockade with the Vm24 scorpion toxin attenuates the CD4+ effector memory T cell response to TCR stimulation. Cell Communication and Signaling 2018, 16, 45 .
AMA StyleJosé Ignacio Veytia-Bucheli, Juana María Jiménez-Vargas, Erika Isabel Melchy-Pérez, Monserrat Alba Sandoval-Hernández, Lourival Domingos Possani, Yvonne Rosenstein. Kv1.3 channel blockade with the Vm24 scorpion toxin attenuates the CD4+ effector memory T cell response to TCR stimulation. Cell Communication and Signaling. 2018; 16 (1):45.
Chicago/Turabian StyleJosé Ignacio Veytia-Bucheli; Juana María Jiménez-Vargas; Erika Isabel Melchy-Pérez; Monserrat Alba Sandoval-Hernández; Lourival Domingos Possani; Yvonne Rosenstein. 2018. "Kv1.3 channel blockade with the Vm24 scorpion toxin attenuates the CD4+ effector memory T cell response to TCR stimulation." Cell Communication and Signaling 16, no. 1: 45.
The consequences of scorpion stings on the affected victims, including humans, have been known since ancient times. The effects of the venom, first on neurotransmission and thereafter on many physiological processes at the organism, tissue, cellular or molecular levels, have been the subject of intense research. It is, therefore, not surprising that a large number of toxins acting on a variety of ion channels have been isolated and described to date. Many of these toxins show high specificities and affinities towards their natural targets. Along with their own biochemical and biophysical characterization, scorpion toxins have been used as invaluable tools for studies regarding the structure and function of ion channels. They have also become important leads in drug development aiming at diagnosing, targeting or direct treatment of channelopathies caused by the improper function of those channels they recognize, as well as other anomalous physiological conditions, including autoimmune diseases and cancer. The main families of scorpion toxins are reviewed here, among which are those specific for Na, K and ryanodine-sensitive Ca channels. The focus is placed on the historical events that led to their discovery and their use in the identification and characterization of the structure and function of ion channels. Their potential use in medicine is also presented.
Ernesto Ortiz; Lourival D. Possani. Scorpion toxins to unravel the conundrum of ion channel structure and functioning. Toxicon 2018, 150, 17 -27.
AMA StyleErnesto Ortiz, Lourival D. Possani. Scorpion toxins to unravel the conundrum of ion channel structure and functioning. Toxicon. 2018; 150 ():17-27.
Chicago/Turabian StyleErnesto Ortiz; Lourival D. Possani. 2018. "Scorpion toxins to unravel the conundrum of ion channel structure and functioning." Toxicon 150, no. : 17-27.