RESUMO
Vasoplegic endothelial dysfunction stands out as one of the most prominent shock syndromes in the intensive care unit, and despite continual therapeutic advances, it is still associated with poor prognosis in critical cases. This scenario is compatible with a significant inflammatory disturbance, with a propensity for increased vascular permeability and deterioration of endothelial response to modulators: a microcirculation disaster. The hemodynamic support's backbone is based primarily on fluid replacement and the use of vasopressor and inotropic agents in nonresponsive patients, aiming to establish a mean arterial pressure of at least 65 mmHg and therefore promote adequate tissue reperfusion. The present study's primary target is to discuss the combination of 3 concepts as a useful strategy for improving results against the high rates of mortality in critically ill patients. These 3 concepts are (1) the use of "broad-spectrum vasopressors," (2) vasopressorsparing strategy, and (3) microcirculation protection.
RESUMO
The Flaviviridae family includes several virus pathogens associated with human diseases worldwide. Within this family, Dengue virus is the most serious threat to public health, especially in tropical and sub-tropical regions of the world. Currently, there are no vaccines or specific antiviral drugs against Dengue virus or against most of the viruses of this family. Therefore, the development of vaccines and the discovery of therapeutic compounds against the medically most important flaviviruses remain a global public health priority. We previously showed that phospholipase A2 isolated from the venom of Crotalus durissus terrificus was able to inhibit Dengue virus and Yellow fever virus infection in Vero cells. Here, we present evidence that phospholipase A2 has a direct effect on Dengue virus particles, inducing a partial exposure of genomic RNA, which strongly suggests inhibition via the cleavage of glycerophospholipids at the virus lipid bilayer envelope. This cleavage might induce a disruption of the lipid bilayer that causes a destabilization of the E proteins on the virus surface, resulting in inactivation. We show by computational analysis that phospholipase A2 might gain access to the Dengue virus lipid bilayer through the pores found on each of the twenty 3-fold vertices of the E protein shell on the virus surface. In addition, phospholipase A2 is able to inactivate other enveloped viruses, highlighting its potential as a natural product lead for developing broad-spectrum antiviral drugs.