The Honorato project's great differential is that it is one of the pioneer projects in Brazil to discuss and study other means of producing an antiophidic drug without the use of animals, in a totally synthetic way! According to the World Health Organization (WHO), it is estimated that annually the number of people bitten by snakes can reach 5.4 million, of this amount, the number of deaths varies between 81,000 and 138,000. In addition, up to 400,000 victims are disabled due to the action of the toxin in the bloodstream. The problem is so serious that the WHO includes accidents with venomous animals, including snakes that produce venom, in its list of neglected tropical diseases.
Snake venom, especially the one from jararaca, is potent and has the capacity to cause serious consequences such as tissue necrosis and hemorrhage, which makes this problem even greater due to the precariousness of the health system in Brazil, considering the people affected are from regions that do not have adequate infrastructure. Thus, besides the possibility of obtaining a drug that reduces the impact of the poison in the human body, avoiding the most serious symptoms: hemorrhage and necrosis, it would be distributed in ampoules, in order to optimize the production process since it is a simpler and faster way to distribute the drug to all regions of the country, besides being easy to store and transport, which would prevent logistical difficulties.
Although this way does not rule out the use of serum, it would avoid more serious problems caused by accidents, which often occur due to the waiting for treatment commonly used, so it would be a quick and immediate response to prevent these more serious consequences. Opting for this alternative treatment, we would have the possibility to better remedy the accidents reaching the entire population, since our proposal is based on the distribution of this drug in health centers and ambulances, so that when these accidents occur the professionals have a quick alternative in hand that will prevent necrosis and hemorrhage, so that the patients have a better response to further treatment.
Throughout our project on Integrated Human Practices we have noticed that there are many wrong ideas propagated about the treatment for ophidian attacks, and that this lack of information most of the time ends up leading to the most serious consequences. Thus, besides the technical study for an alternative treatment, we are also concerned in carrying out projects that bring more information and instructions to the community, thus we are concerned in spreading the information of prevention and correct remediation in case of accidents, so that the chances of serious consequences are minimized.
Analyzing, through bioinformatics, the stability of our protein of interest in ampoules, in order to obtain greater efficiency and agility in relation to the antivenom, was a crucial step in the implementation of the project. Medicines in general are subject to property changes over time due to external and internal factors (SANTOS, 2012; ZHOU et al., 2017). In this context, we developed an analysis of the simulation of the structure, kinetics and molecular dynamics of 𝛾PLI and BJ46a and from it we drew the necessary conclusions to understand the stability conditions of the inhibitor (Check our dry lab page). From the data obtained, we concluded that the stability found by the programs for BJ46a occurred through the solvation of the protein in an aqueous medium with the addition of ions to neutralize the negative charges of the inhibitor, which has an energy of -20,000 e, in addition, we also discovered its molecular mass without the signal peptides, number of atoms in the molecule, its volume and density and the stability temperature which is around 299 K, which is consistent since the snake's habitat is a tropical region, making it believable that its protein is stable at a temperature close to that of its environment.
Analyzing, through bioinformatics and modeling, the stability of our protein of interest in ampoules, in order to achieve greater efficiency and agility compared to antivenom serum, was a crucial step in the implementation of the project. Drugs in general are subject to property changes over time due to external and internal factors. In this context, we developed an analysis of the simulation of the structure, kinetics and molecular dynamics of 𝛾PLI and BJ46a and from it we drew the necessary conclusions to understand the stability conditions of the inhibitor.
For necrotic effects, the theoretical study of 2021 was complemented this year with laboratory experiments on the expression and inhibitory action of 𝛾PLI with phospholipases A2. The joint action of 𝛾PLI and BJ46a, in the form of drugs in ampoules under ideal storage conditions, when applied has the potential to inhibit the necrotic and hemorrhagic effect of the toxic proteins present in the venom.
The evolution of the project in the following years would take place with the laboratory confirmation of our simulations and the in vivo tests of the action of the biosynthetic inhibitor, followed by the approval of the Brazilian Health Regulatory Agency (Anvisa), the regulatory agency linked to the Ministry of Health responsible for the registration of medicines throughout the Brazilian national territory, for large-scale production and distribution in ambulances and health posts. The process of obtaining approval consists of a series of steps: