Triagem virtual de potenciais disruptores do processo de replicação e infecção pelo vírus de Marburg

Abstract

Marburg virus disease is a disease that especially due to its high mortality rate poses a high threat to global sanitary security. The infection is initially dependent on direct or indirect contact with Rousettus aegyptiacus bats or contact with other infected animals, like handling or consumption of bushmeat. Once established the disease may rapidly evolve to more severe conditions with symptoms like hemorrhage, organ failure, and neurological symptoms and even leading to death within a few days after infection and facilitating the spreading between humans through contaminated bodily fluids. Nowadays supportive care, adequate hygiene and increasing awareness are the only ways to control spreading and treating the infected, since there are no available treatments or vaccines. Considering the limitations due to the virus’ high lethality and the danger associated with its research, computer aided drug design becomes an interesting tool for research and development of drugs for its treatment. Computer aided drug design becomes an interesting tool especially for diseases like Marburg virus disease, where the high risk associated with biological systems becomes a significant roadblock. The aim of this study was to evaluate a plethora of natural compounds from two databases, NuBBE and MolPort and their interaction with the Marburg virus’ nucleoprotein (NP). This protein is associated with viral replication and construction and molecules that could alter the protein’s proper function could disturb viral proliferation, postpone the disease’s development and improve prognosis. Two molecules were found within MolPort database (codes 89152 and 5701 in this study) with promising inhibitory potential due to their capabilities of possibly interacting with NP and their favorable toxicological and kinetic properties. These compounds could be further tested in biological systems to assess their role in Marburg virus infection or to be used as building blocks for other compounds to be developed with better pharmacological properties. Furthermore, the use of nucleoproteins as targets is a promising frontier in drug design against negative single stranded RNA viruses considering it is a common protein between virus of this group and its activity in the viral infectious cycle and this study could further consolidate its importance.