34 results on '"Edwards, Caitlin E."'
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2. Norovirus
- Author
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Lindesmith, Lisa C., primary, Verardi, Raffaello, additional, Mallory, Michael L., additional, Edwards, Caitlin E., additional, Graham, Rachel L., additional, Zweigart, Mark R., additional, Brewer-Jensen, Paul D., additional, Debbink, Kari, additional, Kocher, Jacob F., additional, Kwong, Peter D., additional, and Baric, Ralph S., additional
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- 2023
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3. Contributors
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Abzug, Mark J., primary, Acharya, Priyamvada, additional, Acosta, Anna M., additional, Ahmed, S. Sohail, additional, Amanna, Ian J., additional, Anderson, Annaliesa S., additional, Asturias, Edwin J., additional, Bachmann, Martin F., additional, Bahl, Sunil, additional, Bailey, Justin R., additional, Baker, Carol J., additional, Balfour, Henry H., additional, Baric, Ralph S., additional, Barnett, Elizabeth D., additional, Barrett, Alan D.T., additional, Belser, Jessica A., additional, Berzofsky, Jay A., additional, Bethony, Jeffrey M., additional, Brewer-Jensen, Paul D., additional, Bubak, Andrew N., additional, Burns, Cara C., additional, Caplan, Arthur L., additional, Cavaleri, Marco, additional, Chandran, Aruna, additional, Cherian, Thomas, additional, Clemens, John D., additional, Cochino, Emil, additional, Cohet, Catherine, additional, Cohn, Amanda, additional, Cortese, Margaret M., additional, Crowcroft, Natasha S., additional, Curtis, Nigel, additional, Damron, F. Heath, additional, Danchin, Margie, additional, Debbink, Kari, additional, Desai, Sachin N., additional, Davis, Emily H., additional, Decker, Michael D., additional, Denison, Mark R., additional, DeStefano, Frank, additional, Douglas, R. Gordon, additional, Dreher-Lesnick, Sheila M., additional, Eberhardt, Christiane S., additional, Edmunds, W. John, additional, Edwards, Caitlin E., additional, Edwards, Kathryn M., additional, Eggers, Rudolf, additional, Ellis, Ronald, additional, Erdman, Dean D., additional, Ertl, Hildegund C.J., additional, Estivariz, Concepcion F., additional, Fine, Paul E.M., additional, Finn, Theresa M., additional, Fisher, Allison M., additional, Fitzwater, Sean Patrick, additional, Freedman, Mark S., additional, Friede, Martin, additional, Friedlander, Arthur M., additional, Frumento, Nicole, additional, Fry, Alicia M., additional, Garçon, Nathalie, additional, Geris, Jennifer M., additional, Gershon, Anne A., additional, Gervier, Regis, additional, Gessner, Bradford D., additional, Gilbert, Peter B., additional, Gomez, Phillip Louis, additional, Ginsberg, Ann M., additional, Grabenstein, John D., additional, Graham, Rachel L., additional, Graham, Barney S., additional, Granoff, Dan M., additional, Gray, Gregory C., additional, Greenberg, David P., additional, Grohskopf, Lisa A., additional, Gruber, Marion F., additional, Guerena, Fernando B., additional, Havelange, Nicolas, additional, Halstead, Scott B., additional, Hanekom, Willem A., additional, Harrison, Lee H., additional, Hawn, Thomas R., additional, Haynes, Barton F., additional, Healy, C. Mary, additional, Hills, Susan L., additional, Hirabayashi, Kuniko, additional, Holmgren, Jan, additional, Hombach, Joachim M., additional, Hotez, Peter Jay, additional, Howe, Barbara J., additional, Hunegnaw, Ruth, additional, Izopet, Jacques, additional, Jamieson, Denise J., additional, Jansen, Kathrin, additional, Jarrahian, Courtney, additional, Johansen, Kari, additional, Kahn, Geoffrey D., additional, Karron, Ruth A., additional, Katz, Jacqueline M., additional, Kennedy, Richard B., additional, Broojerdi, Alireza Khadem, additional, Khetsuriani, Nino, additional, Khudyakov, Yury, additional, Klugman, Keith P., additional, Kocher, Jacob F., additional, Kollaritsch, Herwig, additional, Kotloff, Karen L., additional, Kozarsky, Phyllis E., additional, Kreimer, Aimée R., additional, Kroger, Andrew T., additional, Kwong, Peter D., additional, Lal, Manjari, additional, Levin, Myron J., additional, Levine, Myron M., additional, Lindesmith, Lisa C., additional, Lindstrand, Ann, additional, Ljungman, Per, additional, Lowy, Douglas R., additional, Lundgren, Anna, additional, Lydon, Patrick, additional, Macklin, Grace R., additional, Maeng, Hoyoung M., additional, Mahalingam, Ravi, additional, Malley, Richard, additional, Mallory, Michael L., additional, Marfin, Anthony A., additional, Markowitz, Lauri E., additional, Marshall, CDR Valerie, additional, McCollum, Andrea, additional, Meyer, Sarah, additional, McNamara, Lucy A., additional, Menning, Lisa, additional, Messacar, Kevin, additional, Miller, Mark A., additional, Milutinovic, Pavle, additional, Modlin, John F., additional, Monath, Thomas P., additional, Morabito, Kaitlyn M., additional, Moss, William J., additional, Mulholland, Kim, additional, Mura, Manuela, additional, Musher, Daniel M., additional, Nagel, Maria A., additional, Nair, G. Balakrish, additional, Nelson, Noele P., additional, Netea, Mihai G., additional, Neuzil, Kathleen Maletic, additional, Niemeyer, Christy S., additional, Nohynek, Hanna, additional, Norheim, Gunnstein, additional, Nussbaum, Lauren, additional, O’Brien, Katherine L., additional, O’Leary, Sean, additional, Ockenhouse, Christian, additional, Offit, Paul A., additional, Okwo-Bele, Jean-Marie, additional, Olkhanud, Purevdorj B., additional, Omer, Saad B., additional, Orenstein, Walter A., additional, Oyston, Petra C.F., additional, Parashar, Umesh D., additional, Patel, Manish M., additional, Payne, Daniel C., additional, Pebody, Richard, additional, Pecetta, Simone, additional, Perlman, Stanley, additional, Pierson, Benjamin, additional, Pierson, Theodore C., additional, Pittet, Laure F., additional, Pittman, Phillip R., additional, Plotkin, Stanley A., additional, Plotkin, Susan L., additional, Poland, Gregory A., additional, Pollard, Sir Andrew John, additional, Poovorawan, Yong, additional, Proctor, Richard A., additional, Qadri, Firdausi, additional, Rao, Agam, additional, Rappuoli, Rino, additional, Reef, Susan E., additional, Rogalewicz, Joseph A., additional, Robinson, James Michael, additional, Roesel, Sigrun, additional, Rubin, Steven A., additional, Rupprecht, Charles E., additional, Rutter, Paul, additional, Samant, Vijay B., additional, Sambhara, Suryaprakash, additional, Samies, Nicole L., additional, Santosham, Mathuram, additional, Saunders, Kevin O., additional, Schiller, John T., additional, Schleiss, Mark R., additional, Schuerman, Lode, additional, Schwab, Jennifer, additional, Schwartz, Jason L., additional, Scobie, Heather M., additional, Scott, J. Anthony, additional, Shapiro, Eugene D., additional, Shenoy, Erica S., additional, Shimabukuro, Tom T., additional, Shouval, Daniel, additional, Siegrist, Claire-Anne, additional, Sitrin, Robert D., additional, Skinner, Nicole E., additional, Slifka, Mark K., additional, Sodha, Samir V., additional, Soeters, Heidi M., additional, Solomon, Tom, additional, Speiser, Daniel E., additional, Staples, J. Erin, additional, Steffen, Robert, additional, Stephens, David S., additional, Strebel, Peter M., additional, Subbarao, Kanta, additional, Sullivan, Nancy J., additional, Takashima, Yoshihiro, additional, Tate, Jacqueline E., additional, Tayman, Alice, additional, Telford, Sam R., additional, Thombley, Melisa, additional, Thomsen, Isaac, additional, Tohme, Rania A., additional, Trabold, Malin, additional, El-Turabi, Aadil, additional, Vaughn, David W., additional, Verardi, Raffaello, additional, Vicari, Andrea S., additional, Vidor, Emmanuel J., additional, Villafana, Tonya, additional, Vogt, Matthew R., additional, Walker, Mark J., additional, Walsh, Nick M., additional, Wanlapakorn, Nasamon, additional, Ward, John W., additional, Wassilak, Steven G.F., additional, Watts, Lisa A., additional, Weber, David J., additional, Weiner, David B., additional, Weng, Mark K., additional, Wexler, Deborah L., additional, Wharton, Melinda, additional, Whitley, Richard J., additional, Whitney, Cynthia G., additional, Wiehe, Kevin, additional, Williamson, E. Diane, additional, Wormser, Gary P., additional, Xia, Ningshao, additional, Yildirim, Inci, additional, Zehrung, Darin, additional, and Zweigart, Mark R., additional
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- 2023
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4. Human lung organoids as a model for respiratory virus replication and countermeasure performance in human hosts
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Edwards, Caitlin E., Tata, Aleksandra, and Baric, Ralph S.
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- 2022
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5. Swine acute diarrhea syndrome coronavirus replication in primary human cells reveals potential susceptibility to infection
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Edwards, Caitlin E., Yount, Boyd L., Graham, Rachel L., Leist, Sarah R., Hou, Yixuan J., Dinnon, Kenneth H., Sims, Amy C., Swanstrom, Jesica, Gully, Kendra, Scobey, Trevor D., Cooley, Michelle R., Currie, Caroline G., Randell, Scott H., and Baric, Ralph S.
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- 2020
6. Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction
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Katsura, Hiroaki, Sontake, Vishwaraj, Tata, Aleksandra, Kobayashi, Yoshihiko, Edwards, Caitlin E., Heaton, Brook E., Konkimalla, Arvind, Asakura, Takanori, Mikami, Yu, Fritch, Ethan J., Lee, Patty J., Heaton, Nicholas S., Boucher, Richard C., Randell, Scott H., Baric, Ralph S., and Tata, Purushothama Rao
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- 2020
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7. A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice
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Leist, Sarah R., Dinnon, Kenneth H., III, Schäfer, Alexandra, Tse, Longping V., Okuda, Kenichi, Hou, Yixuan J., West, Ande, Edwards, Caitlin E., Sanders, Wes, Fritch, Ethan J., Gully, Kendra L., Scobey, Trevor, Brown, Ariane J., Sheahan, Timothy P., Moorman, Nathaniel J., Boucher, Richard C., Gralinski, Lisa E., Montgomery, Stephanie A., and Baric, Ralph S.
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- 2020
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8. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract
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Hou, Yixuan J., Okuda, Kenichi, Edwards, Caitlin E., Martinez, David R., Asakura, Takanori, Dinnon, Kenneth H., III, Kato, Takafumi, Lee, Rhianna E., Yount, Boyd L., Mascenik, Teresa M., Chen, Gang, Olivier, Kenneth N., Ghio, Andrew, Tse, Longping V., Leist, Sarah R., Gralinski, Lisa E., Schäfer, Alexandra, Dang, Hong, Gilmore, Rodney, Nakano, Satoko, Sun, Ling, Fulcher, M. Leslie, Livraghi-Butrico, Alessandra, Nicely, Nathan I., Cameron, Mark, Cameron, Cheryl, Kelvin, David J., de Silva, Aravinda, Margolis, David M., Markmann, Alena, Bartelt, Luther, Zumwalt, Ross, Martinez, Fernando J., Salvatore, Steven P., Borczuk, Alain, Tata, Purushothama R., Sontake, Vishwaraj, Kimple, Adam, Jaspers, Ilona, O’Neal, Wanda K., Randell, Scott H., Boucher, Richard C., and Baric, Ralph S.
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- 2020
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9. Virus–Host Interactions Between Nonsecretors and Human Norovirus
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Lindesmith, Lisa C., Brewer-Jensen, Paul D., Mallory, Michael L., Jensen, Kara, Yount, Boyd L., Costantini, Veronica, Collins, Matthew H., Edwards, Caitlin E., Sheahan, Timothy P., Vinjé, Jan, and Baric, Ralph S.
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- 2020
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10. A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures
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Dinnon, Kenneth H., III, Leist, Sarah R., Schäfer, Alexandra, Edwards, Caitlin E., Martinez, David R., Montgomery, Stephanie A., and West, Ande
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Homeopathy -- Materia medica and therapeutics ,Therapeutics -- Evaluation ,Therapeutics, Experimental ,Mice -- Models -- Testing ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Coronaviruses are prone to transmission to new host species, as recently demonstrated by the spread to humans of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic.sup.1. Small animal models that recapitulate SARS-CoV-2 disease are needed urgently for rapid evaluation of medical countermeasures.sup.2,3. SARS-CoV-2 cannot infect wild-type laboratory mice owing to inefficient interactions between the viral spike protein and the mouse orthologue of the human receptor, angiotensin-converting enzyme 2 (ACE2).sup.4. Here we used reverse genetics.sup.5 to remodel the interaction between SARS-CoV-2 spike protein and mouse ACE2 and designed mouse-adapted SARS-CoV-2 (SARS-CoV-2 MA), a recombinant virus that can use mouse ACE2 for entry into cells. SARS-CoV-2 MA was able to replicate in the upper and lower airways of both young adult and aged BALB/c mice. SARS-CoV-2 MA caused more severe disease in aged mice, and exhibited more clinically relevant phenotypes than those seen in Hfh4-ACE2 transgenic mice, which express human ACE2 under the control of the Hfh4 (also known as Foxj1) promoter. We demonstrate the utility of this model using vaccine-challenge studies in immune-competent mice with native expression of mouse ACE2. Finally, we show that the clinical candidate interferon-[lambda]1a (IFN-[lambda]1a) potently inhibits SARS-CoV-2 replication in primary human airway epithelial cells in vitro--both prophylactic and therapeutic administration of IFN-[lambda]1a diminished SARS-CoV-2 replication in mice. In summary, the mouse-adapted SARS-CoV-2 MA model demonstrates age-related disease pathogenesis and supports the clinical use of pegylated IFN-[lambda]1a as a treatment for human COVID-19.sup.6. A model in mouse using a species-adapted virus recapitulates features of SARS-CoV-2 infection and age-related disease pathogenesis in humans, and provides a model system for rapid evaluation of medical countermeasures against coronavirus disease 2019 (COVID-19)., Author(s): Kenneth H. Dinnon III [sup.1] , Sarah R. Leist [sup.2] , Alexandra Schäfer [sup.2] , Caitlin E. Edwards [sup.2] , David R. Martinez [sup.2] , Stephanie A. Montgomery [sup.3] [...]
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- 2020
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11. Progenitor identification and SARS-CoV-2 infection in human distal lung organoids
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Salahudeen, Ameen A., Choi, Shannon S., Rustagi, Arjun, Zhu, Junjie, van Unen, Vincent, de la O, Sean M., Flynn, Ryan A., Margalef-Català, Mar, Santos, António J. M., Ju, Jihang, Batish, Arpit, Usui, Tatsuya, Zheng, Grace X. Y., Edwards, Caitlin E., Wagar, Lisa E., Luca, Vincent, Anchang, Benedict, Nagendran, Monica, Nguyen, Khanh, Hart, Daniel J., Terry, Jessica M., Belgrader, Phillip, Ziraldo, Solongo B., Mikkelsen, Tarjei S., Harbury, Pehr B., Glenn, Jeffrey S., Garcia, K. Christopher, Davis, Mark M., Baric, Ralph S., Sabatti, Chiara, Amieva, Manuel R., Blish, Catherine A., Desai, Tushar J., and Kuo, Calvin J.
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- 2020
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12. Disulfide stabilization of human norovirus GI.1 virus-like particles focuses immune response toward blockade epitopes
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Verardi, Raffaello, Lindesmith, Lisa C., Tsybovsky, Yaroslav, Gorman, Jason, Chuang, Gwo-Yu, Edwards, Caitlin E., Brewer-Jensen, Paul D., Mallory, Michael L., Ou, Li, Schön, Arne, Shi, Wei, Tully, Ena S., Georgiou, George, Baric, Ralph S., and Kwong, Peter D.
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- 2020
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13. Publisher Correction: A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures
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Dinnon, III, Kenneth H., Leist, Sarah R., Schäfer, Alexandra, Edwards, Caitlin E., Martinez, David R., Montgomery, Stephanie A., West, Ande, Yount, Jr, Boyd L., Hou, Yixuan J., Adams, Lily E., Gully, Kendra L., Brown, Ariane J., Huang, Emily, Bryant, Matthew D., Choong, Ingrid C., Glenn, Jeffrey S., Gralinski, Lisa E., Sheahan, Timothy P., and Baric, Ralph S.
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- 2021
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14. Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease
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Kato, Takafumi, primary, Asakura, Takanori, additional, Edwards, Caitlin E., additional, Dang, Hong, additional, Mikami, Yu, additional, Okuda, Kenichi, additional, Chen, Gang, additional, Sun, Ling, additional, Gilmore, Rodney C., additional, Hawkins, Padraig, additional, De la Cruz, Gabriela, additional, Cooley, Michelle R., additional, Bailey, Alexis B., additional, Hewitt, Stephen M., additional, Chertow, Daniel S., additional, Borczuk, Alain C., additional, Salvatore, Steven, additional, Martinez, Fernando J., additional, Thorne, Leigh B., additional, Askin, Frederic B., additional, Ehre, Camille, additional, Randell, Scott H., additional, O’Neal, Wanda K., additional, Baric, Ralph S., additional, and Boucher, Richard C., additional
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- 2022
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15. Chapter 43 - Norovirus
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Lindesmith, Lisa C., Verardi, Raffaello, Mallory, Michael L., Edwards, Caitlin E., Graham, Rachel L., Zweigart, Mark R., Brewer-Jensen, Paul D., Debbink, Kari, Kocher, Jacob F., Kwong, Peter D., and Baric, Ralph S.
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- 2023
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16. Pharmacokinetic-based failure of a detergent virucidal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) nasal infections: A preclinical study and randomized controlled trial
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Esther, Charles R., Huang, Li Ching, Edwards, Caitlin E., Pickles, Raymond J., Baric, Ralph S., Kimple, Adam J., Kimura, Kyle S., Randell, Scott H., Freeman, Michael H., Wessinger, Bronson C., Von Wahlde, Kate, Strickland, Britton A., Turner, Justin H., Mikami, Yu, Boucher, Richard C., Kato, Takafumi, Bacon, Daniel R., Gupta, Veerain C., Sheng, Quanhu, Das, Suman R., Ceppe, Agathe S., and Brown, Hunter M.
- Abstract
BACKGROUND: The nose is the portal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, suggesting the nose as a target for topical antiviral therapies. The purpose of this study was to assess both the in vivo and in vitro efficacy of a detergent-based virucidal agent, Johnson and Johnson's Baby Shampoo (J&J), in SARS-CoV-2-infected subjects. METHODS: Subjects were randomized into three treatment groups: (1) twice daily nasal irrigation with J&J in hypertonic saline, (2) hypertonic saline alone, and (3) no intervention. Complementary in vitro experiments were performed in cultured human nasal epithelia. The primary outcome measure in the clinical trial was change in SARS-CoV-2 viral load over 21 days. Secondary outcomes included symptom scores and change in daily temperature. Outcome measures for in vitro studies included change in viral titers. RESULTS: Seventy-two subjects completed the clinical study (n = 24 per group). Despite demonstrated safety and robust efficacy in in vitro virucidal assays, J&J irrigations had no impact on viral titers or symptom scores in treated subjects relative to controls. Similar findings were observed administering J&J to infected cultured human airway epithelia using protocols mimicking the clinical trial regimen. Additional studies of cultured human nasal epithelia demonstrated that lack of efficacy reflected pharmacokinetic failure, with the most virucidal J&J detergent components rapidly absorbed from nasal surfaces. CONCLUSION: In this randomized clinical trial of subjects with SARS-CoV-2 infection, a topical detergent-based virucidal agent had no effect on viral load or symptom scores. Complementary in vitro studies confirmed a lack of efficacy, reflective of pharmacokinetic failure and rapid absorption from nasal surfaces.
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- 2022
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17. Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease
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Martinez, Fernando J., Edwards, Caitlin E, Chertow, Daniel S., Hawkins, Padraig, Chen, Gang, NIH COVID-19 Autopsy Consortium, Boucher, Richard C, Ehre, Camille, Gilmore, Rodney C, Dang, Hong, Okuda, Kenichi, Borczuk, Alain C, Mikami, Yu, Randell, Scott H, De la Cruz, Gabriela, Thorne, Leigh B, Sun, Ling, Cooley, Michelle R, Kato, Takafumi, Salvatore, Steven, Bailey, Alexis B, O'Neal, Wanda K, Baric, Ralph S., Askin, Frederic B, Asakura, Takanori, and Hewitt, Stephen M
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Rationale: The incidence and sites of mucus accumulation, and molecular regulation of mucin gene expression, in COVID-19 lung disease have not been reported. Objectives: Characterize incidence of mucus accumulation and the mechanisms mediating mucin hypersecretion in COVID-19 lung disease. Methods: Airway mucus and mucins were evaluated in COVID-19 autopsy lungs by AB-PAS and immunohistochemical staining, RNA in situ hybridization, and spatial transcriptional profiling. SARS-CoV-2-infected human bronchial epithelial (HBE) cultures were utilized to investigate mechanisms of SARS-CoV-2-induced mucin expression and synthesis and test candidate countermeasures. Measurements and Main Results: MUC5B and variably MUC5AC RNA levels were increased throughout all airway regions of COVID-19 autopsy lungs, notably in the sub-acute/chronic disease phase following SARS-CoV-2 clearance. In the distal lung, MUC5B-dominated mucus plugging was observed in 90% of COVID-19 subjects in both morphologically identified bronchioles and microcysts, and MUC5B accumulated in damaged alveolar spaces. SARS-CoV-2-infected HBE cultures exhibited peak titers 3 days post inoculation, whereas induction of MUC5B/MUC5AC peaked 7-14 days post inoculation. SARS-CoV-2 infection of HBE cultures induced expression of EGFR ligands and inflammatory cytokines (e.g., IL-1α/β) associated with mucin gene regulation. Inhibiting EGFR/IL-1R pathways, or dexamethasone administration, reduced SARS-CoV-2-induced mucin expression. Conclusions: SARS-CoV-2 infection is associated with a high prevalence of distal airspace mucus accumulation and increased MUC5B expression in COVID-19 autopsy lungs. HBE culture studies identified roles for EGFR and IL-1R signaling in mucin gene regulation post SARS-CoV-2 infection. These data suggest that time-sensitive mucolytic agents, specific pathway inhibitors, or corticosteroid administration may be therapeutic for COVID-19 lung disease. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org.libproxy.lib.unc.edu/licenses/by-nc-nd/4.0/).
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- 2022
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18. SARS-CoV-2 infection of airway cells causes intense viral and cell shedding, two spreading mechanisms affected by IL-13
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Morrison, Cameron B., primary, Edwards, Caitlin E., additional, Shaffer, Kendall M., additional, Araba, Kenza C., additional, Wykoff, Jason A., additional, Williams, Danielle R., additional, Asakura, Takanori, additional, Dang, Hong, additional, Morton, Lisa C., additional, Gilmore, Rodney C., additional, O’Neal, Wanda K., additional, Boucher, Richard C., additional, Baric, Ralph S., additional, and Ehre, Camille, additional
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- 2022
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19. Pharmacokinetic‐based failure of a detergent virucidal for severe acute respiratory syndrome–coronavirus‐2 (SARS‐CoV‐2) nasal infections: A preclinical study and randomized controlled trial
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Esther, Charles R., primary, Kimura, Kyle S., additional, Mikami, Yu, additional, Edwards, Caitlin E., additional, Das, Suman R., additional, Freeman, Michael H., additional, Strickland, Britton A., additional, Brown, Hunter M., additional, Wessinger, Bronson C., additional, Gupta, Veerain C., additional, Von Wahlde, Kate, additional, Sheng, Quanhu, additional, Huang, Li Ching, additional, Bacon, Daniel R., additional, Kimple, Adam J., additional, Ceppe, Agathe S., additional, Kato, Takafumi, additional, Pickles, Raymond J., additional, Randell, Scott H., additional, Baric, Ralph S., additional, Turner, Justin H., additional, and Boucher, Richard C., additional
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- 2022
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20. Thiol-based chemical probes exhibit antiviral activity against SARS-CoV-2 via allosteric disulfide disruption in the spike glycoprotein
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Shi, Yunlong, primary, Zeida, Ari, additional, Edwards, Caitlin E., additional, Mallory, Michael L., additional, Sastre, Santiago, additional, Machado, Matías R., additional, Pickles, Raymond J., additional, Fu, Ling, additional, Liu, Keke, additional, Yang, Jing, additional, Baric, Ralph S., additional, Boucher, Richard C., additional, Radi, Rafael, additional, and Carroll, Kate S., additional
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- 2022
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21. Thiol-based mucolytics exhibit antiviral activity against SARS-CoV-2 through allosteric disulfide disruption in the spike glycoprotein
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Shi, Yunlong, primary, Zeida, Ari, additional, Edwards, Caitlin E., additional, Mallory, Michael L., additional, Sastre, Santiago, additional, Machado, Matías R., additional, Pickles, Raymond J., additional, Fu, Ling, additional, Liu, Keke, additional, Yang, Jing, additional, Baric, Ralph S., additional, Boucher, Richard C., additional, Radi, Rafael, additional, and Carroll, Kate S., additional
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- 2021
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22. Pharmacokinetic-based failure of a detergent virucidal for SARS-COV-2 nasal infections
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Esther, Charles R., primary, Kimura, Kyle S., additional, Mikami, Yu, additional, Edwards, Caitlin E., additional, Das, Suman R., additional, Freeman, Michael H., additional, Strickland, Britton A., additional, Brown, Hunter M., additional, Wessinger, Bronson C., additional, Gupta, Veerain C., additional, Von Wahlde, Kate, additional, Sheng, Quanhu, additional, Huang, Li Ching, additional, Bacon, Daniel R., additional, Kimple, Adam J., additional, Ceppe, Agathe S., additional, Kato, Takafumi, additional, Pickles, Raymond J., additional, Randell, Scott H., additional, Baric, Ralph S., additional, Turner, Justin H., additional, and Boucher, Richard C., additional
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- 2021
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23. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo
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Hou, Yixuan J., primary, Chiba, Shiho, additional, Halfmann, Peter, additional, Ehre, Camille, additional, Kuroda, Makoto, additional, Dinnon, Kenneth H., additional, Leist, Sarah R., additional, Schäfer, Alexandra, additional, Nakajima, Noriko, additional, Takahashi, Kenta, additional, Lee, Rhianna E., additional, Mascenik, Teresa M., additional, Graham, Rachel, additional, Edwards, Caitlin E., additional, Tse, Longping V., additional, Okuda, Kenichi, additional, Markmann, Alena J., additional, Bartelt, Luther, additional, de Silva, Aravinda, additional, Margolis, David M., additional, Boucher, Richard C., additional, Randell, Scott H., additional, Suzuki, Tadaki, additional, Gralinski, Lisa E., additional, Kawaoka, Yoshihiro, additional, and Baric, Ralph S., additional
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- 2020
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24. SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo
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Hou, Yixuan J., primary, Chiba, Shiho, additional, Halfmann, Peter, additional, Ehre, Camille, additional, Kuroda, Makoto, additional, Dinnon, Kenneth H, additional, Leist, Sarah R., additional, Schäfer, Alexandra, additional, Nakajima, Noriko, additional, Takahashi, Kenta, additional, Lee, Rhianna E., additional, Mascenik, Teresa M., additional, Edwards, Caitlin E., additional, Tse, Longping V., additional, Boucher, Richard C., additional, Randell, Scott H., additional, Suzuki, Tadaki, additional, Gralinski, Lisa E., additional, Kawaoka, Yoshihiro, additional, and Baric, Ralph S., additional
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- 2020
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25. Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures
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Salahudeen, Ameen A., primary, Choi, Shannon S., additional, Rustagi, Arjun, additional, Zhu, Junjie, additional, de la O, Sean M., additional, Flynn, Ryan A., additional, Margalef-Català, Mar, additional, Santos, António J. M., additional, Ju, Jihang, additional, Batish, Arpit, additional, van Unen, Vincent, additional, Usui, Tatsuya, additional, Zheng, Grace X.Y., additional, Edwards, Caitlin E., additional, Wagar, Lisa E., additional, Luca, Vincent, additional, Anchang, Benedict, additional, Nagendran, Monica, additional, Nguyen, Khanh, additional, Hart, Daniel J., additional, Terry, Jessica M., additional, Belgrader, Phillip, additional, Ziraldo, Solongo B., additional, Mikkelsen, Tarjei S., additional, Harbury, Pehr B., additional, Glenn, Jeffrey S., additional, Garcia, K. Christopher, additional, Davis, Mark M., additional, Baric, Ralph S., additional, Sabatti, Chiara, additional, Amieva, Manuel R., additional, Blish, Catherine A., additional, Desai, Tushar J., additional, and Kuo, Calvin J., additional
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- 2020
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26. The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients
- Author
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Premkumar, Lakshmanane, primary, Segovia-Chumbez, Bruno, additional, Jadi, Ramesh, additional, Martinez, David R., additional, Raut, Rajendra, additional, Markmann, Alena J., additional, Cornaby, Caleb, additional, Bartelt, Luther, additional, Weiss, Susan, additional, Park, Yara, additional, Edwards, Caitlin E., additional, Weimer, Eric, additional, Scherer, Erin M., additional, Rouphael, Nadine, additional, Edupuganti, Srilatha, additional, Weiskopf, Daniela, additional, Tse, Longping V., additional, Hou, Yixuan J., additional, Margolis, David, additional, Sette, Alessandro, additional, Collins, Matthew H., additional, Schmitz, John, additional, Baric, Ralph S., additional, and de Silva, Aravinda M., additional
- Published
- 2020
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27. The RBD Of The Spike Protein Of SARS-Group Coronaviruses Is A Highly Specific Target Of SARS-CoV-2 Antibodies But Not Other Pathogenic Human and Animal Coronavirus Antibodies
- Author
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Premkumar, Lakshmanane, primary, Segovia-Chumbez, Bruno, additional, Jadi, Ramesh, additional, Martinez, David R., additional, Raut, Rajendra, additional, Markmann, Alena, additional, Cornaby, Caleb, additional, Bartelt, Luther, additional, Weiss, Susan, additional, Park, Yara, additional, Edwards, Caitlin E., additional, Weimer, Eric, additional, Scherer, Erin M., additional, Roupael, Nadine, additional, Edupuganti, Sri, additional, Weiskopf, Daniela, additional, Tse, Longping V., additional, Hou, Yixuan J., additional, Margolis, David, additional, Sette, Alessandro, additional, Collins, Matthew H., additional, Schmitz, John, additional, Baric, Ralph S., additional, and de Silva, Aravinda M., additional
- Published
- 2020
- Full Text
- View/download PDF
28. A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures
- Author
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Dinnon, Kenneth H., primary, Leist, Sarah R., additional, Schäfer, Alexandra, additional, Edwards, Caitlin E., additional, Martinez, David R., additional, Montgomery, Stephanie A., additional, West, Ande, additional, Yount, Boyd L., additional, Hou, Yixuan J., additional, Adams, Lily E., additional, Gully, Kendra L., additional, Brown, Ariane J., additional, Huang, Emily, additional, Bryant, Matthew D., additional, Choong, Ingrid C., additional, Glenn, Jeffrey S., additional, Gralinski, Lisa E., additional, Sheahan, Timothy P., additional, and Baric, Ralph S., additional
- Published
- 2020
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- View/download PDF
29. Thiol-based chemical probes exhibit antiviral activity against SARS-CoV-2 via allosteric disulfide disruption in the spike glycoprotein.
- Author
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Yunlong Shi, Zeida, Ari, Edwards, Caitlin E., Mallory, Michael L., Sastre, Santiago, Machado, Matías R., Pickles, Raymond J., Ling Fu, Keke Liu, Jing Yang, Baric, Ralph S., Boucher, Richard C., Radi, Rafael, and Carroll, Kate S.
- Subjects
SARS-CoV-2 ,ANGIOTENSIN converting enzyme ,REDUCING agents ,COVID-19 pandemic ,FIREPROOFING agents ,CORONAVIRUSES - Abstract
The development of small-molecules targeting different components of SARS-CoV-2 is a key strategy to complement antibody-based treatments and vaccination campaigns in managing the COVID-19 pandemic. Here, we show that two thiol-based chemical probes that act as reducing agents, P2119 and P2165, inhibit infection by human coronaviruses, including SARS-CoV-2, and decrease the binding of spike glycoprotein to its receptor, the angiotensin-converting enzyme 2 (ACE2). Proteomics and reactive cysteine pro-filing link the antiviral activity to the reduction of key disulfides, specifically by disruption of the Cys379-Cys432 and Cys391-Cys525 pairs distal to the receptor binding motif in the receptor binding domain (RBD) of the spike glycoprotein. Computational analyses provide insight into conformation changes that occur when these disulfides break or form, consistent with an allosteric role, and indicate that P2119/P2165 target a conserved hydrophobic binding pocket in the RBD with the benzyl thiol-reducing moiety pointed directly toward Cys432. These collective findings establish the vulnerability of human coronaviruses to thiol-based chemical probes and lay the groundwork for developing compounds of this class, as a strategy to inhibit the SARS-CoV-2 infection by shifting the spike glycoprotein redox scaffold. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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30. Pharmacokinetic-based failure of a detergent virucidal for SARS-COV-2 nasal infections.
- Author
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Esther CR Jr, Kimura KS, Mikami Y, Edwards CE, Das SR, Freeman MH, Strickland BA, Brown HM, Wessinger BC, Gupta VC, Von Wahlde K, Sheng Q, Huang LC, Bacon DR, Kimple AJ, Ceppe AS, Kato T, Pickles RJ, Randell SH, Baric RS, Turner JH, and Boucher RC
- Abstract
The nose is the portal for SARS-CoV-2 infection, suggesting the nose as a target for topical antiviral therapies. Because detergents are virucidal, Johnson and Johnson's Baby Shampoo (J&J) was tested as a topical virucidal agent in SARS-CoV-2 infected subjects. Twice daily irrigation of J&J in hypertonic saline, hypertonic saline alone, or no intervention were compared (n = 24/group). Despite demonstrated safety and robust efficacy in in vitro virucidal assays, J&J irrigations had no impact on viral titers or symptom scores in treated subjects relative to controls. Similar findings were observed administering J&J to infected cultured human airway epithelia using protocols mimicking the clinical trial regimen. Additional studies of cultured human nasal epithelia demonstrated that lack of efficacy reflected pharmacokinetic failure, with the most virucidal J&J detergent components rapidly absorbed from nasal surfaces. This study emphasizes the need to assess the pharmacokinetic characteristics of virucidal agents on airway surfaces to guide clinical trials.
- Published
- 2021
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31. SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo .
- Author
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Hou YJ, Chiba S, Halfmann P, Ehre C, Kuroda M, Dinnon KH 3rd, Leist SR, Schäfer A, Nakajima N, Takahashi K, Lee RE, Mascenik TM, Edwards CE, Tse LV, Boucher RC, Randell SH, Suzuki T, Gralinski LE, Kawaoka Y, and Baric RS
- Abstract
The D614G substitution in the S protein is most prevalent SARS-CoV-2 strain circulating globally, but its effects in viral pathogenesis and transmission remain unclear. We engineered SARS-CoV-2 variants harboring the D614G substitution with or without nanoluciferase. The D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype (WT) virus in competition studies. With similar morphology to the WT virion, the D614G virus is also more sensitive to SARS-CoV-2 neutralizing antibodies. Infection of human ACE2 transgenic mice and Syrian hamsters with the WT or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. Our study demonstrated the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission.
- Published
- 2020
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32. Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures.
- Author
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Salahudeen AA, Choi SS, Rustagi A, Zhu J, de la O SM, Flynn RA, Margalef-Català M, Santos AJM, Ju J, Batish A, van Unen V, Usui T, Zheng GXY, Edwards CE, Wagar LE, Luca V, Anchang B, Nagendran M, Nguyen K, Hart DJ, Terry JM, Belgrader P, Ziraldo SB, Mikkelsen TS, Harbury PB, Glenn JS, Garcia KC, Davis MM, Baric RS, Sabatti C, Amieva MR, Blish CA, Desai TJ, and Kuo CJ
- Abstract
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or KRT5
+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid KRT5+ cells contained a distinct ITGA6+ ITGB4+ mitotic population whose proliferation segregated to a TNFRSF12Ahi subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12Ahi subset of FACS-purified ITGA6+ ITGB4+ basal cells from human lung or derivative organoids. In vivo, TNFRSF12A+ cells comprised ~10% of KRT5+ basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 apical-out organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.- Published
- 2020
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33. The RBD Of The Spike Protein Of SARS-Group Coronaviruses Is A Highly Specific Target Of SARS-CoV-2 Antibodies But Not Other Pathogenic Human and Animal Coronavirus Antibodies.
- Author
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Premkumar L, Segovia-Chumbez B, Jadi R, Martinez DR, Raut R, Markmann A, Cornaby C, Bartelt L, Weiss S, Park Y, Edwards CE, Weimer E, Scherer EM, Roupael N, Edupuganti S, Weiskopf D, Tse LV, Hou YJ, Margolis D, Sette A, Collins MH, Schmitz J, Baric RS, and de Silva AM
- Abstract
A new Severe Acute Respiratory Syndrome Coronavirus variant (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus present with clinically inapparent, mild or severe disease. Currently, the presence of the virus in individual patients and at the population level is being monitored by testing symptomatic cases by PCR for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the viral spike (S) protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV specific antibodies in people. Here we use a large panel of human sera (70 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate the performance of the RBD as an antigen for accurate detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) to antibodies induced by SARS-CoVs. We observed a robust correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, strongly support the use of RBD-based antibody assays for population-level surveillance and as a correlate of neutralizing antibody levels in people who have recovered from SARS-CoV-2 infections.
- Published
- 2020
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34. A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures.
- Author
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Dinnon KH, Leist SR, Schäfer A, Edwards CE, Martinez DR, Montgomery SA, West A, Yount BL, Hou YJ, Adams LE, Gully KL, Brown AJ, Huang E, Bryant MD, Choong IC, Glenn JS, Gralinski LE, Sheahan TP, and Baric RS
- Abstract
Coronaviruses are prone to emergence into new host species most recently evidenced by SARS-CoV-2, the causative agent of the COVID-19 pandemic. Small animal models that recapitulate SARS-CoV-2 disease are desperately needed to rapidly evaluate medical countermeasures (MCMs). SARS-CoV-2 cannot infect wildtype laboratory mice due to inefficient interactions between the viral spike (S) protein and the murine ortholog of the human receptor, ACE2. We used reverse genetics to remodel the S and mACE2 binding interface resulting in a recombinant virus (SARS-CoV-2 MA) that could utilize mACE2 for entry. SARS-CoV-2 MA replicated in both the upper and lower airways of both young adult and aged BALB/c mice. Importantly, disease was more severe in aged mice, and showed more clinically relevant phenotypes than those seen in hACE2 transgenic mice. We then demonstrated the utility of this model through vaccine challenge studies in immune competent mice with native expression of mACE2. Lastly, we show that clinical candidate interferon (IFN) lambda-1a can potently inhibit SARS-CoV-2 replication in primary human airway epithelial cells in vitro , and both prophylactic and therapeutic administration diminished replication in mice. Our mouse-adapted SARS-CoV-2 model demonstrates age-related disease pathogenesis and supports the clinical use of IFN lambda-1a treatment in human COVID-19 infections.
- Published
- 2020
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