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2. A tripartite cocktail of chimeric monoclonal antibodies passively protects mice against ricin, staphylococcal enterotoxin B and Clostridium perfringens epsilon toxin

Author

Sully, Erin K, Whaley, Kevin, Bohorova, Natasha, Bohorov, Ognian, Goodman, Charles, Kim, Do, Pauly, Michael, Velasco, Jesus, Holtsberg, Frederick W, Stavale, Eric, Aman, M Javad, Tangudu, Chandra, Uzal, Francisco A, Mantis, Nicholas J, and Zeitlin, Larry

Subjects
Biotechnology, Biodefense, Infectious Diseases, Prevention, Foodborne Illness, Immunization, Emerging Infectious Diseases, Vaccine Related, Animals, Antibodies, Monoclonal, Bacterial Toxins, Bioterrorism, Enterotoxins, Female, Mice, Mice, Inbred BALB C, Neutralization Tests, Poisoning, Recombinant Fusion Proteins, Ricin, Antibody, Toxin, Therapeutic, Pharmacology and Pharmaceutical Sciences, Toxicology
Abstract

Due to the fast-acting nature of ricin, staphylococcal enterotoxin B (SEB), and Clostridium perfringens epsilon toxin (ETX), it is necessary that therapeutic interventions following a bioterrorism incident by one of these toxins occur as soon as possible after intoxication. Moreover, because the clinical manifestations of intoxication by these agents are likely to be indistinguishable from each other, especially following aerosol exposure, we have developed a cocktail of chimeric monoclonal antibodies that is capable of neutralizing all three toxins. The efficacy of this cocktail was demonstrated in mouse models of lethal dose toxin challenge.

Published
2014

3. Persistence of Ebola virus after the end of widespread transmission in Liberia: an outbreak report

Author

Dokubo, Emily Kainne, Wendland, Annika, Mate, Suzanne E, Ladner, Jason T, Hamblion, Esther L, Raftery, Philomena, Blackley, David J, Laney, A Scott, Mahmoud, Nuha, Wayne-Davies, Gloria, Hensley, Lisa, Stavale, Eric, Fakoli, Lawrence, Gregory, Christopher, Chen, Tai-Ho, Koryon, Augustine, Roth Allen, Denise, Mann, Jennifer, Hickey, Andrew, Saindon, John, Badini, Mehboob, Baller, April, Clement, Peter, Bolay, Fatorma, Wapoe, Yatta, Wiley, Michael R, Logue, James, Dighero-Kemp, Bonnie, Higgs, Elizabeth, Gasasira, Alex, Williams, Desmond E, Dahn, Bernice, Kateh, Francis, Nyenswah, Tolbert, Palacios, Gustavo, and Fallah, Mosoka P

Published
2018
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8. Natural History of Marburg Virus Infection to Support Medical Countermeasure Development

Author

Comer, Jason E., primary, Brasel, Trevor, additional, Massey, Shane, additional, Beasley, David W., additional, Cirimotich, Chris M., additional, Sanford, Daniel C., additional, Chou, Ying-Liang, additional, Niemuth, Nancy A., additional, Novak, Joseph, additional, Sabourin, Carol L., additional, Merchlinsky, Michael, additional, Long, James P., additional, Stavale, Eric J., additional, and Wolfe, Daniel N., additional

Published
2022
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9. Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia

Author

Kennedy, Stephen B., Bolay, Fatorma, Kieh, Mark, Grandits, Greg, Badio, Moses, Ballou, Ripley, Eckes, Risa, Feinberg, Mark, Follmann, Dean, Grund, Birgit, Gupta, Swati, Hensley, Lisa, Higgs, Elizabeth, Janosko, Krisztina, Johnson, Melvin, Kateh, Francis, Logue, James, Marchand, Jonathan, Monath, Thomas, Nason, Martha, Nyenswah, Tolbert, Roman, François, Stavale, Eric, Wolfson, Julian, Neaton, James D., and Lane, Clifford H.

Published
2017
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15. Assessment and Optimization of the GeneXpert Diagnostic Platform for Detection of Ebola Virus RNA in Seminal Fluid

Author

Pettitt, James, primary, Higgs, Elizabeth, additional, Fallah, Mosoka, additional, Nason, Martha, additional, Stavale, Eric, additional, Marchand, Jonathan, additional, Reilly, Cavan, additional, Jensen, Kenneth, additional, Dighero-Kemp, Bonnie, additional, Tuznik, Kaylie, additional, Logue, James, additional, Bolay, Fatorma, additional, and Hensley, Lisa, additional

Published
2016
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16. A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)

Author

Warfield, Kelly, primary, Plummer, Emily, additional, Alonzi, Dominic, additional, Wolfe, Gary, additional, Sampath, Aruna, additional, Nguyen, Tam, additional, Butters, Terry, additional, Enterlein, Sven, additional, Stavale, Eric, additional, Shresta, Sujan, additional, and Ramstedt, Urban, additional

Published
2015
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18. The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication

Author

Carocci, Margot, primary, Hinshaw, Stephen M., additional, Rodgers, Mary A., additional, Villareal, Valerie A., additional, Burri, Dominique J., additional, Pilankatta, Rajendra, additional, Maharaj, Natalya P., additional, Gack, Michaela U., additional, Stavale, Eric J., additional, Warfield, Kelly L., additional, and Yang, Priscilla L., additional

Published
2015
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19. Novel Benzoxazole Inhibitor of Dengue Virus Replication That Targets the NS3 Helicase

Author

Byrd, Chelsea M., primary, Grosenbach, Douglas W., additional, Berhanu, Aklile, additional, Dai, Dongcheng, additional, Jones, Kevin F., additional, Cardwell, Kara B., additional, Schneider, Christine, additional, Yang, Guang, additional, Tyavanagimatt, Shanthakumar, additional, Harver, Chris, additional, Wineinger, Kristin A., additional, Page, Jessica, additional, Stavale, Eric, additional, Stone, Melialani A., additional, Fuller, Kathleen P., additional, Lovejoy, Candace, additional, Leeds, Janet M., additional, Hruby, Dennis E., additional, and Jordan, Robert, additional

Published
2013
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20. A Novel Inhibitor of Dengue Virus Replication That Targets the Capsid Protein

Author

Byrd, Chelsea M., primary, Dai, Dongcheng, additional, Grosenbach, Douglas W., additional, Berhanu, Aklile, additional, Jones, Kevin F., additional, Cardwell, Kara B., additional, Schneider, Christine, additional, Wineinger, Kristin A., additional, Page, Jessica M., additional, Harver, Chris, additional, Stavale, Eric, additional, Tyavanagimatt, Shanthakumar, additional, Stone, Melialani A., additional, Bartenschlager, Ralf, additional, Scaturro, Pietro, additional, Hruby, Dennis E., additional, and Jordan, Robert, additional

Published
2013
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21. Inhibiting Early-Stage Events in HIV-1 Replication by Small-Molecule Targeting of the HIV-1 Capsid

Author

Kortagere, Sandhya, primary, Madani, Navid, additional, Mankowski, Marie K., additional, Schön, Arne, additional, Zentner, Isaac, additional, Swaminathan, Gokul, additional, Princiotto, Amy, additional, Anthony, Kevin, additional, Oza, Apara, additional, Sierra, Luz-Jeannette, additional, Passic, Shendra R., additional, Wang, Xiaozhao, additional, Jones, David M., additional, Stavale, Eric, additional, Krebs, Fred C., additional, Martín-García, Julio, additional, Freire, Ernesto, additional, Ptak, Roger G., additional, Sodroski, Joseph, additional, Cocklin, Simon, additional, and Smith, Amos B., additional

Published
2012
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22. Synthetic Human Monoclonal Antibodies toward Staphylococcal Enterotoxin B (SEB) Protective against Toxic Shock Syndrome

Author

Karauzum, Hatice, primary, Chen, Gang, additional, Abaandou, Laura, additional, Mahmoudieh, Mahta, additional, Boroun, Atefeh R., additional, Shulenin, Sergey, additional, Devi, V. Sathya, additional, Stavale, Eric, additional, Warfield, Kelly L., additional, Zeitlin, Larry, additional, Roy, Chad J., additional, Sidhu, Sachdev S., additional, and Aman, M. Javad, additional

Published
2012
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23. Modulation of GSK-3β Activity in Venezuelan Equine Encephalitis Virus Infection

Author

Kehn-Hall, Kylene, primary, Narayanan, Aarthi, additional, Lundberg, Lindsay, additional, Sampey, Gavin, additional, Pinkham, Chelsea, additional, Guendel, Irene, additional, Van Duyne, Rachel, additional, Senina, Svetlana, additional, Schultz, Kimberly L., additional, Stavale, Eric, additional, Aman, M. Javad, additional, Bailey, Charles, additional, and Kashanchi, Fatah, additional

Published
2012
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24. Small Molecule HIV-1 Capsid Inhibitor Design using Hybrid Structure Based Methods

Author

Kortagere, Sandhya, primary, Madani, Navid, additional, Mankowski, Marie K., additional, Princiotto, Amy, additional, Anthony, Kevin, additional, Sierra, Luz-Jeannette, additional, Wang, Xiaozhao, additional, Jones, David M., additional, Courter, Joel R., additional, Stavale, Eric, additional, Ptak, Roger, additional, Smith, Amos B., additional, Martín-García, Julio, additional, Sodroski, Joseph, additional, and Cocklin, Simon, additional

Published
2011
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25. The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication

Author

Carocci, Margot, Hinshaw, Stephen M., Rodgers, Mary A., Villareal, Valerie A., Burri, Dominique J., Pilankatta, Rajendra, Maharaj, Natalya P., Gack, Michaela U., Stavale, Eric J., Warfield, Kelly L., and Yang, Priscilla L.

Abstract

ABSTRACTDengue virus (DENV), a member of the Flaviviridaefamily, is a mosquito-borne pathogen and the cause of dengue fever. The increasing prevalence of DENV worldwide heightens the need for an effective vaccine and specific antivirals. Due to the dependence of DENV upon the lipid biosynthetic machinery of the host cell, lipid signaling and metabolism present unique opportunities for inhibiting viral replication. We screened a library of bioactive lipids and modulators of lipid metabolism and identified 4-hydroxyphenyl retinamide (4-HPR) (fenretinide) as an inhibitor of DENV in cell culture. 4-HPR inhibits the steady-state accumulation of viral genomic RNA and reduces viremia when orally administered in a murine model of DENV infection. The molecular target responsible for this antiviral activity is distinct from other known inhibitors of DENV but appears to affect other members of the Flaviviridae, including the West Nile, Modoc, and hepatitis C viruses. Although long-chain ceramides have been implicated in DENV replication, we demonstrate that DENV is insensitive to the perturbation of long-chain ceramides in mammalian cell culture and that the effect of 4-HPR on dihydroceramide homeostasis is separable from its antiviral activity. Likewise, the induction of reactive oxygen species by 4-HPR is not required for the inhibition of DENV. The inhibition of DENV in vivoby 4-HPR, combined with its well-established safety and tolerability in humans, suggests that it may be repurposed as a pan-Flaviviridaeantiviral agent. This work also illustrates the utility of bioactive lipid screens for identifying critical interactions of DENV and other viral pathogens with host lipid biosynthesis, metabolism, and signal transduction.

Published
2014
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26. A Novel Inhibitor of Dengue Virus Replication That Targets the Capsid Protein

Author

Byrd, Chelsea M., Dai, Dongcheng, Grosenbach, Douglas W., Berhanu, Aklile, Jones, Kevin F., Cardwell, Kara B., Schneider, Christine, Wineinger, Kristin A., Page, Jessica M., Harver, Chris, Stavale, Eric, Tyavanagimatt, Shanthakumar, Stone, Melialani A., Bartenschlager, Ralf, Scaturro, Pietro, Hruby, Dennis E., and Jordan, Robert

Abstract

ABSTRACTDengue viruses (DENV) infect 50 to 100 million people worldwide per year, of which 500,000 develop severe life-threatening disease. This mosquito-borne illness is endemic in most tropical and subtropical countries and has spread significantly over the last decade. While there are several promising vaccine candidates in clinical trials, there are currently no approved vaccines or therapeutics available for treatment of dengue infection. Here, we describe a novel small-molecule compound, ST-148, that is a potent inhibitor of all four serotypes of DENV in vitro. ST-148 significantly reduced viremia and viral load in vital organs and tended to lower cytokine levels in the plasma in a nonlethal model of DENV infection in AG129 mice. Compound resistance mapped to the DENV capsid (C) gene, and a direct interaction of ST-148 with C protein is suggested by alterations of the intrinsic fluorescence of the protein in the presence of compound. Thus, ST-148 appears to interact with the DENV C protein and inhibits a distinct step(s) of the viral replication cycle.

Published
2012
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