ORCID Profile
0000-0003-2779-9564
Current Organisation
Universidade Estadual Paulista Júlio de Mesquita Filho
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Publisher: Springer Science and Business Media LLC
Date: 24-01-2019
DOI: 10.1038/S41598-018-36839-6
Abstract: Ophidian accidents are considered an important neglected tropical disease by the World Health Organization. Particularly in Latin America, Bothrops snakes are responsible for the majority of the snakebite envenomings that are not efficiently treated by conventional serum therapy. Thus, the search for simple and efficient inhibitors to complement this therapy is a promising research area, and a combination of functional and structural assays have been used to test candidate ligands against specific ophidian venom compounds. Herein, we tested a commercial drug (acetylsalicylic acid, ASA) and a plant compound with antiophidian properties (rosmarinic acid, RA) using myographic, crystallographic and bioinformatics experiments with a phospholipase A 2 -like toxin, MjTX-II. MjTX-II/RA and MjTX-II/ASA crystal structures were solved at high resolution and revealed the presence of ligands bound to different regions of the toxin. However, in vitro myographic assays showed that only RA is able to prevent the myotoxic effects of MjTX-II. In agreement with functional results, molecular dynamics simulations showed that the RA molecule remains tightly bound to the toxin throughout the calculations, whereas ASA molecules tend to dissociate. This approach aids the design of effective inhibitors of PLA 2 -like toxins and, eventually, may complement serum therapy.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.IJBIOMAC.2017.04.013
Abstract: Snake venoms contain various proteins, especially phospholipases A
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.BIOCHI.2020.01.010
Abstract: Envenoming by snakebite is an important global health issue that has received little attention, leading the World Health Organization to naming it as neglected tropical disease. Several snakebites present serious local symptoms manifested on victims that may not be efficiently neutralized by serum therapy. Phospholipase A
Publisher: Public Library of Science (PLoS)
Date: 21-12-2011
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.BBAGEN.2016.08.003
Abstract: One of the main challenges in snakebite envenomation treatment is the development of stable, versatile and efficient anti-venom therapies. Local myotoxicity in accidents involving snakes from the Bothrops genus is still a consequence of serum therapy inefficient neutralization that may lead to permanent sequelae in their victims. One of the classes of toxins that participate in muscle necrosis is the PLA Myographic and electrophysiological techniques were used to evaluate the inhibitory effect of zinc ions, isothermal titration calorimetry assays were used to measure the affinity between zinc ions and the toxin and X-ray crystallography was used to reveal details of this interaction. We demonstrated that zinc ions can effectively inhibit the toxin by the interaction with two different sites, which are related to two different mechanism of inhibition: preventing membrane disruption and impairing the toxin state transition. Furthermore, structural study presented here included an additional step in the current myotoxic mechanism improving the comprehension of the allosteric transition that PLA Our findings show that zinc ions are inhibitors of PLA Zinc is a new candidate that can assist in anti-venom treatments and can promote the design of new and even more accurate structure-based inhibitors for PLA
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.BBAGEN.2018.08.002
Abstract: Specific compounds found in vegetal species have been demonstrated to be efficient inhibitors of snake toxins, such as phospholipase A Myographic and histological techniques were used to evaluate the inhibitory effect of chicoric acid (CA) against BthTX-I myotoxin. Isothermal titration calorimetry assays were used to measure the affinity between the inhibitor and the toxin. X-ray crystallography was used to reveal details of this interaction. CA prevented the blockade of indirectly evoked muscle contraction and inhibited muscle damage induced by BthTX-I. The inhibitor binds to the toxin with the highest affinity measured for a natural compound in calorimetric assays. The crystal structure and molecular dynamics simulations demonstrated that CA binds at the entrance of the hydrophobic channel of the toxin and binds to one of the clusters that participates in membrane disruption. CA prevents the myotoxic activity of the toxin, preventing its activation by simultaneous binding with two critical regions. CA is a potential myotoxic inhibitor to other PLA
Publisher: Elsevier BV
Date: 08-2021
Publisher: Public Library of Science (PLoS)
Date: 20-07-2015
Location: Brazil
No related grants have been discovered for Fábio Florença Cardoso.