Document text
Principal Investigator: Lijun Rong
Organization: UNIVERSITY OF ILLINOIS AT CHICAGO
Fiscal Year: 2022
Award: $795,165
Funding agency: National Institute of Allergy and Infectious Diseases
Summary
Ebola virus disease (EVD) is caused by an infection with a group of viruses within the
genus Ebolavirus. There are at least five species of Ebolavirus, Ebola virus (Zaire,
EBOV), Ebola Sudan (SUDV), Bundibugyo virus (BDBV), Reston virus and Tai Forest
virus (TAFV). Infections with these viruses can cause severe hemorrhagic fevers in
humans and nonhuman primates, and are associated with up to 90% mortality rates with
EBOV. Because of the safety concerns, these viruses are designated as the biosafety
level 4 agents. Currently there is no effective therapeutic treatments against Ebola virus
infection and pathogenesis in humans. Thus the goal of this application is to develop
GP-specific small molecule inhibitors as drugs which can be used prophylactically and
therapeutically against EBOV and other Ebola virus infections. To achieve this, we
screened an in-house library of small molecules, and identified numerous potent entry
inhibitors against EBOV. We have identified a series of potent compounds and will use
them as leads which will be chemically optimized and developed as an anti-Ebola virus
therapy candidate. In this application, two specific aims are proposed: (1) structure-
based optimization of the lead compounds, and (2) In vivo evaluation of the lead
compounds against EBOV infection using animal models.
Terms: <Animal Model><Animal Models and Related Studies><Antiviral Therapy><Assay><BDBV><Belgian Congo><Binding><Bioassay><Biologic Assays><Biological Assay><Bundibugyo ebola virus><Bundibugyo ebolavirus><Bundibugyo virus><Characteristics><Chemicals><Clinic><Complex><Democratic Republic of the Congo><Dose><Drug Kinetics><Drugs><EBOV><Ebola><Ebola Hemorrhagic Fever><Ebola Virus Disease><Ebola disease><Ebola virus><Ebola-like Viruses><Estrogen Receptors><Exhibits><GP1><GP2><GP2 gene><GTP-Binding Protein 1><GTPBP1><GTPBP1 gene><Glycoprotein 2, Zymogen Granule Membrane><Glycoproteins><Goals><Human><In Vitro><Incidence><Infection><Lead><Libraries><Life><Ligands><Maximal Tolerated Dose><Maximally Tolerated Dose><Maximum Tolerated Dose><Mediating><Medical><Medication><Mice><Mice Mammals><Modern Man><Molecular Interaction><Murine><Mus><Pb element><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacokinetics><Prevalence><Property><RESTV><Reporting><Research><Resolution><Reston Ebola virus><Reston ebolavirus><Reston virus><Route><SERMs><SUDV><Safety><Selective Estrogen Receptor Modulators><Series><Structure><Sudan><Sudan Ebola virus><Sudan ebolavirus><Sudan virus><Tamoxifen><Therapeutic><Time><Toremifene><Toxicokinetics><Viral><Viral Diseases><Viral Hemorrhagic Fevers><Viral Pathogenesis><Virus><Virus Diseases><Work><Zaire><Zoonoses><Zoonotic><Zoonotic Infection><Zymogen Granule Membrane Glycoprotein 2><analog><anti-viral development><anti-viral drug development><anti-viral therapeutic development><anti-viral therapy><anti-viral therapy development><antiviral development><antiviral drug development><antiviral therapeutic development><antiviral therapy development><base><chemical library><cost><developing anti-viral agent><developing anti-viral drug><developing anti-viral therapeutic><developing anti-viral therapy><developing antiviral agent><developing antiviral drug><developing antiviral therapeutic><developing antiviral therapy><drug/agent><ebolavirus><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><forest><guinea pig model><heavy metal Pb><heavy metal lead><hemorrhagic fever><in vivo evaluation><in vivo testing><inhibitor><lead optimization><model of animal><model organism><mortality><non-human primate><nonhuman primate><novel><pre-clinical><preclinical><prophylactic><remote location><scaffold><scaffolding><scale up><side effect><small molecule><small molecule inhibitor><small molecule libraries><therapeutic candidate><therapeutic target><therapeutically effective><viral infection><viral infectious disease treatment><virus infection><virus pathogenesis><virus-induced disease>