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Antimyotoxic Activity of Synthetic Peptides Derived from Bothrops atrox Snake Gamma Phospholipase A2 Inhibitor Selected by Virtual Screening

[ Vol. 19 , Issue. 22 ]

Author(s):

J.C. Sobrinho, A.F. Francisco, R. Simões-Silva, A.M. Kayano, J.J. Alfonso Ruiz Diaz, A.F. Gomez Garay, A. Arruda, A.S. Ferreira, A.P.A. Santos, M.B. Luiz, C.B.G. Teles, S.S. Pereira, F.B. Zanchi, L.A. Calderon, J.P. Zuliani and A.M. Soares*   Pages 1952 - 1961 ( 10 )

Abstract:


Background: Several studies have aimed to identify molecules that inhibit the toxic actions of snake venom phospholipases A2 (PLA2s). Studies carried out with PLA2 inhibitors (PLIs) have been shown to be efficient in this assignment.

Objective: This work aimed to analyze the interaction of peptides derived from Bothrops atrox PLIγ (atPLIγ) with a PLA2 and to evaluate the ability of these peptides to reduce phospholipase and myotoxic activities.

Methods: Peptides were subjected to molecular docking with a homologous Lys49 PLA2 from B. atrox venom modeled by homology. Phospholipase activity neutralization assay was performed with BthTX-II and different ratios of the peptides. A catalytically active and an inactive PLA2 were purified from the B. atrox venom and used together in the in vitro myotoxic activity neutralization experiments with the peptides.

Results: The peptides interacted with amino acids near the PLA2 hydrophobic channel and the loop that would be bound to calcium in Asp49 PLA2. They were able to reduce phospholipase activity and peptides DFCHNV and ATHEE reached the highest reduction levels, being these two peptides the best that also interacted in the in silico experiments. The peptides reduced the myotubes cell damage with a highlight for the DFCHNV peptide, which reduced by about 65%. It has been suggested that myotoxic activity reduction is related to the sites occupied in the PLA2 structure, which could corroborate the results observed in molecular docking.

Conclusion: This study should contribute to the investigation of the potential of PLIs to inhibit the toxic effects of PLA2s.

Keywords:

Snake envenomation, PLIγ inhibitor, Coupling phospholipase A2-inhibitor, Peptides derived, Antimyotoxic activity, Virtual screening.

Affiliation:

Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Laboratório de Engenharia de Anticorpos, Fiocruz Rondônia, Porto Velho-RO, Laboratório da Plataforma de Bioensaios de Malária e Leishmaniose, Fiocruz Rondônia, Porto Velho-RO, Laboratório da Plataforma de Bioensaios de Malária e Leishmaniose, Fiocruz Rondônia, Porto Velho-RO, Laboratório de Engenharia de Anticorpos, Fiocruz Rondônia, Porto Velho-RO, Laboratório da Plataforma de Bioensaios de Malária e Leishmaniose, Fiocruz Rondônia, Porto Velho-RO, Laboratório de Engenharia de Anticorpos, Fiocruz Rondônia, Porto Velho-RO, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia

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