benzofurans and Hemorrhagic-Fever--Ebola

Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients.

Topics: Amides; Amidines; Androstenes; Animals; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antiviral Agents; Benzofurans; Cytosine; Disease Models, Animal; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Immune Sera; Organophosphonates; Pyrazines; RNA, Small Interfering; Stilbenes; Virus Replication

Topics: Amino Acids; Antibodies, Neutralizing; Antiviral Agents; Benzofurans; COVID-19 Drug Treatment; Dengue; Diterpenes; Hemorrhagic Fever, Ebola; Humans; Molecular Docking Simulation; Monkeypox virus; Proline; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Valine; Zika Virus

There exists an urgent need to develop licensed drugs and vaccines for the treatment or prevention of filovirus infections. FGI-103 is a low-molecular-weight compound that was discovered through an in vitro screening assay utilizing a variant of Zaire ebolavirus (ZEBOV) that expresses green fluorescent protein. In vitro analyses demonstrated that FGI-103 also exhibits antiviral activity against wild-type ZEBOV and Sudan ebolavirus, as well as Marburgvirus (MARV) strains Ci67 and Ravn. In vivo administration of FGI-103 as a single intraperitoneal dose of 10 mg/kg delivered 24 h after infection is sufficient to completely protect mice against a lethal challenge with a mouse-adapted strain of either ZEBOV or MARV-Ravn. In a murine model of ZEBOV infection, delivery of FGI-103 reduces viremia and the viral burden in kidney, liver, and spleen tissues and is associated with subdued and delayed proinflammatory cytokine responses and tissue pathology. Taken together, these results identify a promising antiviral therapeutic candidate for the treatment of filovirus infections.

Topics: Amidines; Animals; Antiviral Agents; Benzofurans; Chlorocebus aethiops; Cytokines; Ebolavirus; Female; Filoviridae; Filoviridae Infections; Green Fluorescent Proteins; Hemorrhagic Fever, Ebola; Hep G2 Cells; Humans; Kidney; Liver; Male; Marburg Virus Disease; Marburgvirus; Mice; Mice, Inbred C57BL; Molecular Weight; Small Molecule Libraries; Vero Cells