Strategies in Medicinal Chemistry to Discovery New Hits Compounds Against Ebola Virus: Challenges and Perspectives in Drug Discovery.

Ebola virus (EBOV) is an infectious disease that mainly affects the cardiovascular system. It belongs to the Filoviridae family, consisting of filamentous envelopes, non-segmented negative RNA genome. EBOV was initially identified in Sudan and Zaire (now named the Democratic Republic of Congo), around 1967. It is transmitted mainly by contact with secretions (blood, sweat, saliva, and tears) from infected wild animals, such as non-human primates and bats. It has gained more prominence in recent years, due to the recent EBOV outbreaks that occurred from 2013 to 2016, resulting in approximately 28,000 infected individuals, with a mortality rate of 40-70%, affecting mainly Liberia, Guinea, and Sierra Leone. Despite these alarming levels, there is no FDA-approved drug for the effective treatment of these diseases until now. The most advanced drug to treat EBOV is remdesivir. However, it is a high-cost drug and is available only for intravenous use. In sense, more investments are needed in the research focused on the development of new antiviral drugs. In this context, medicinal chemistry strategies have been improving and increasingly providing the discovery of new hits that can be used in the future as a treatment against these diseases. Thus, this review will address the main advances in medicinal chemistry, such as drug discovery through computational techniques (virtual screening and virtual high throughput screening), in addition drug repurposing, phenotypic screening assays, and employing classical medicinal chemistry, such as bioisosterism, metabolism-based drug design and the discovery of new inhibitors through natural products, presenting several compounds promising that may contain the advance of these pathogens.