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1. Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination

Author

Adams, Lily E., Leist, Sarah R., Dinnon, Kenneth H., III, West, Ande, Gully, Kendra L., Anderson, Elizabeth J., Loome, Jennifer F., Madden, Emily A., Powers, John M., Schäfer, Alexandra, Sarkar, Sanjay, Castillo, Izabella N., Maron, Jenny S., McNamara, Ryan P., Bertera, Harry L., Zweigart, Mark R., Higgins, Jaclyn S., Hampton, Brea K., Premkumar, Lakshmanane, Alter, Galit, Montgomery, Stephanie A., Baxter, Victoria K., Heise, Mark T., and Baric, Ralph S.

Published
2023
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3. An Immunocompetent Mouse Model of Zika Virus Infection.

Author

Gorman, Matthew J, Caine, Elizabeth A, Zaitsev, Konstantin, Begley, Matthew C, Weger-Lucarelli, James, Uccellini, Melissa B, Tripathi, Shashank, Morrison, Juliet, Yount, Boyd L, Dinnon, Kenneth H, Rückert, Claudia, Young, Michael C, Zhu, Zhe, Robertson, Shelly J, McNally, Kristin L, Ye, Jing, Cao, Bin, Mysorekar, Indira U, Ebel, Gregory D, Baric, Ralph S, Best, Sonja M, Artyomov, Maxim N, Garcia-Sastre, Adolfo, and Diamond, Michael S

Subjects
Brain, Placenta, Animals, Mice, Inbred C57BL, Mice, Transgenic, Humans, Mice, Pregnancy Complications, Infectious, Fetal Diseases, Disease Models, Animal, Serine Endopeptidases, RNA Helicases, Homeodomain Proteins, Interferons, Interferon-beta, Viral Nonstructural Proteins, Cell Survival, Immunity, Pregnancy, Mutation, Female, STAT2 Transcription Factor, Receptor, Interferon alpha-beta, Infectious Disease Transmission, Vertical, Zika Virus, Zika Virus Infection, RNA sequencing, Zika virus, flavivirus, immunity, infectious clone, interferon, pathogenesis, pregnancy, transgenic mice, vertical transmission, Inbred C57BL, Transgenic, Pregnancy Complications, Infectious, Disease Models, Animal, Receptor, Interferon alpha-beta, Infectious Disease Transmission, Vertical, Microbiology, Medical Microbiology, Immunology
Abstract

Progress toward understanding Zika virus (ZIKV) pathogenesis is hindered by lack of immunocompetent small animal models, in part because ZIKV fails to effectively antagonize Stat2-dependent interferon (IFN) responses in mice. To address this limitation, we first passaged an African ZIKV strain (ZIKV-Dak-41525) through Rag1-/- mice to obtain a mouse-adapted virus (ZIKV-Dak-MA) that was more virulent than ZIKV-Dak-41525 in mice treated with an anti-Ifnar1 antibody. A G18R substitution in NS4B was the genetic basis for the increased replication, and resulted in decreased IFN-β production, diminished IFN-stimulated gene expression, and the greater brain infection observed with ZIKV-Dak-MA. To generate a fully immunocompetent mouse model of ZIKV infection, human STAT2 was introduced into the mouse Stat2 locus (hSTAT2 KI). Subcutaneous inoculation of pregnant hSTAT2 KI mice with ZIKV-Dak-MA resulted in spread to the placenta and fetal brain. An immunocompetent mouse model of ZIKV infection may prove valuable for evaluating countermeasures to limit disease.

Published
2018

4. A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry

Author

Le Pen, Jeremie, primary, Paniccia, Gabrielle, additional, Bauer, Michael, additional, Hoffmann, H.-Heinrich, additional, Kinast, Volker, additional, Moncada-Velez, Marcela, additional, Pinharanda, Ana, additional, Ricardo-Lax, Inna, additional, Stenzel, Ansgar F, additional, Rosado-Olivieri, Edwin A, additional, Ashbrook, Alison W, additional, Dinnon, Kenneth H, additional, Doyle, William, additional, Freije, Catherine, additional, Hong, Seon-Hui, additional, Lee, Danyel, additional, Lewy, Tyler, additional, Luna, Joseph M, additional, Peace, Avery, additional, Schmidt, Carltin, additional, Schneider, Willia M, additional, Winkler, Roni, additional, Larson, Chloe, additional, McGinn, Timothy, additional, Menezes, Miriam-Rose, additional, Ramos-Espiritu, Lavoisier, additional, Banerjee, Priyam, additional, Poirier, John T, additional, Sanchez-Rivera, Francisco J, additional, Zhang, Qian, additional, Casanova, Jean-Laurent, additional, Carroll, Thomas S, additional, Glickman, J. Fraser, additional, Michailidis, Eleftherios, additional, Razooky, Brandon, additional, MacDonald, Margaret R, additional, and Rice, Charles M, additional

Published
2024
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5. Stabilized coronavirus spike stem elicits a broadly protective antibody

Author

Hsieh, Ching-Lin, Werner, Anne P., Leist, Sarah R., Stevens, Laura J., Falconer, Ester, Goldsmith, Jory A., Chou, Chia-Wei, Abiona, Olubukola M., West, Ande, Westendorf, Kathryn, Muthuraman, Krithika, Fritch, Ethan J., Dinnon, Kenneth H., III, Schäfer, Alexandra, Denison, Mark R., Chappell, James D., Baric, Ralph S., Graham, Barney S., Corbett, Kizzmekia S., and McLellan, Jason S.

Published
2021
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7. SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801

Author

Wahl, Angela, Gralinski, Lisa E., Johnson, Claire E., Yao, Wenbo, Kovarova, Martina, Dinnon, Kenneth H., III, Liu, Hongwei, Madden, Victoria J., Krystek, Halina M., De, Chandrav, White, Gregory R., Kolykhalov, Alexander A., Natchus, Michael G., Askin, Frederic B., Painter, George, Browne, Edward P., and Jones, Corbin D.

Subjects
Antiviral agents -- Testing, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

All coronaviruses known to have recently emerged as human pathogens probably originated in bats.sup.1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801--an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials--markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19. Human and bat coronaviruses replicate efficiently in immunodeficient mice implanted with human lung tissue, and treatment or prophylaxis using EIDD-2801 in this model suggests that this oral antiviral agent may be effective in preventing COVID-19., Author(s): Angela Wahl [sup.1] [sup.2] [sup.3] , Lisa E. Gralinski [sup.4] , Claire E. Johnson [sup.1] [sup.2] [sup.3] , Wenbo Yao [sup.1] [sup.2] [sup.3] , Martina Kovarova [sup.1] [sup.2] [sup.3] [...]

Published
2021
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8. Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population

Author

Cruz Cisneros, Marta C., primary, Anderson, Elizabeth J., additional, Hampton, Brea K., additional, Parotti, Breantié, additional, Sarkar, Sanjay, additional, Taft-Benz, Sharon, additional, Bell, Timothy A., additional, Blanchard, Matthew, additional, Dillard, Jacob A., additional, Dinnon, Kenneth H., additional, Hock, Pablo, additional, Leist, Sarah R., additional, Madden, Emily A., additional, Shaw, Ginger D., additional, West, Ande, additional, Baric, Ralph S., additional, Baxter, Victoria K., additional, Pardo-Manuel de Villena, Fernando, additional, Heise, Mark T., additional, and Ferris, Martin T., additional

Published
2024
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9. A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures

Author

Dinnon, Kenneth H., III, Leist, Sarah R., Schäfer, Alexandra, Edwards, Caitlin E., Martinez, David R., Montgomery, Stephanie A., and West, Ande

Subjects
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] [...]

Published
2020
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10. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

Author

Corbett, Kizzmekia S., Edwards, Darin K., Leist, Sarah R., Abiona, Olubukola M., Boyoglu-Barnum, Seyhan, Gillespie, Rebecca A., Himansu, Sunny, Schäfer, Alexandra, Ziwawo, Cynthia T., DiPiazza, Anthony T., Dinnon, Kenneth H., Elbashir, Sayda M., Shaw, Christine A., Woods, Angela, Fritch, Ethan J., Martinez, David R., Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Hutchinson, Geoffrey B., Wu, Kai, Henry, Carole, Bahl, Kapil, Garcia-Dominguez, Dario, Ma, LingZhi, Renzi, Isabella, Kong, Wing-Pui, Schmidt, Stephen D., Wang, Lingshu, Zhang, Yi, Phung, Emily, Chang, Lauren A., Loomis, Rebecca J., Altaras, Nedim Emil, Narayanan, Elisabeth, Metkar, Mihir, Presnyak, Vlad, Liu, Cuiping, Louder, Mark K., Shi, Wei, Leung, Kwanyee, Yang, Eun Sung, West, Ande, Gully, Kendra L., Stevens, Laura J., Wang, Nianshuang, Wrapp, Daniel, Doria-Rose, Nicole A., Stewart-Jones, Guillaume, Bennett, Hamilton, Alvarado, Gabriela S., Nason, Martha C., Ruckwardt, Tracy J., McLellan, Jason S., Denison, Mark R., Chappell, James D., Moore, Ian N., Morabito, Kaitlyn M., Mascola, John R., Baric, Ralph S., Carfi, Andrea, and Graham, Barney S.

Published
2020
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13. Mouse Adapted SARS-CoV-2 (MA10) Viral Infection Induces Neuroinflammation in Standard Laboratory Mice

Author

Amruta, Narayanappa, primary, Ismael, Saifudeen, additional, Leist, Sarah R., additional, Gressett, Timothy E., additional, Srivastava, Akhilesh, additional, Dinnon, Kenneth H., additional, Engler-Chiurazzi, Elizabeth B., additional, Maness, Nicholas J., additional, Qin, Xuebin, additional, Kolls, Jay K., additional, Baric, Ralph S., additional, and Bix, Gregory, additional

Published
2022
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14. Fc mediated pan-sarbecovirus protection after alphavirus vector vaccination

Author

Adams, Lily E., primary, Leist, Sarah R., additional, Dinnon, Kenneth H., additional, West, Ande, additional, Gully, Kendra L., additional, Anderson, Elizabeth J., additional, Loome, Jennifer F., additional, Madden, Emily A., additional, Powers, John M., additional, Schäfer, Alexandra, additional, Sarkar, Sanjay, additional, Castillo, Izabella N., additional, Maron, Jenny S., additional, McNamara, Ryan P., additional, Bertera, Harry L., additional, Zweigert, Mark R., additional, Higgins, Jaclyn S., additional, Hampton, Brea K., additional, Premkumar, Lakshmanane, additional, Alter, Galit, additional, Montgomery, Stephanie A., additional, Baxter, Victoria K., additional, Heise, Mark T., additional, and Baric, Ralph S., additional

Published
2022
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15. SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice

Author

Dinnon, Kenneth H., primary, Leist, Sarah R., additional, Okuda, Kenichi, additional, Dang, Hong, additional, Fritch, Ethan J., additional, Gully, Kendra L., additional, De la Cruz, Gabriela, additional, Evangelista, Mia D., additional, Asakura, Takanori, additional, Gilmore, Rodney C., additional, Hawkins, Padraig, additional, Nakano, Satoko, additional, West, Ande, additional, Schäfer, Alexandra, additional, Gralinski, Lisa E., additional, Everman, Jamie L., additional, Sajuthi, Satria P., additional, Zweigart, Mark R., additional, Dong, Stephanie, additional, McBride, Jennifer, additional, Cooley, Michelle R., additional, Hines, Jesse B., additional, Love, Miriya K., additional, Groshong, Steve D., additional, VanSchoiack, Alison, additional, Phelan, Stefan J., additional, Liang, Yan, additional, Hether, Tyler, additional, Leon, Michael, additional, Zumwalt, Ross E., additional, Barton, Lisa M., additional, Duval, Eric J., additional, Mukhopadhyay, Sanjay, additional, Stroberg, Edana, additional, Borczuk, Alain, additional, Thorne, Leigh B., additional, Sakthivel, Muthu K., additional, Lee, Yueh Z., additional, Hagood, James S., additional, Mock, Jason R., additional, Seibold, Max A., additional, O’Neal, Wanda K., additional, Montgomery, Stephanie A., additional, Boucher, Richard C., additional, and Baric, Ralph S., additional

Published
2022
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16. Investigation of the Host Kinome Response to Coronavirus Infection Reveals PI3K/mTOR Inhibitors as Betacoronavirus Antivirals

Author

Fritch, Ethan J., Mordant, Angie L., Gilbert, Thomas S.K., Wells, Carrow I., Yang, Xuan, Barker, Natalie K., Madden, Emily A., Dinnon, Kenneth H., Hou, Yixuan J., Tse, Longping V., Castillo, Izabella N., Sims, Amy C., Moorman, Nathaniel J., Lakshmanane, Premkumar, Willson, Timothy M., Herring, Laura E., Graves, Lee M., and Baric, Ralph S.

Abstract

Host kinases play essential roles in the host cell cycle, innate immune signaling, the stress response to viral infection, and inflammation. Previous work has demonstrated that coronaviruses specifically target kinase cascades to subvert host cell responses to infection and rely upon host kinase activity to phosphorylate viral proteins to enhance replication. Given the number of kinase inhibitors that are already FDA approved to treat cancers, fibrosis, and other human disease, they represent an attractive class of compounds to repurpose for host-targeted therapies against emerging coronavirus infections. To further understand the host kinome response to betacoronavirus infection, we employed multiplex inhibitory bead mass spectrometry (MIB-MS) following MERS-CoV and SARS-CoV-2 infection of human lung epithelial cell lines. Our MIB-MS analyses revealed activation of mTOR and MAPK signaling following MERS-CoV and SARS-CoV-2 infection, respectively. SARS-CoV-2 host kinome responses were further characterized using paired phosphoproteomics, which identified activation of MAPK, PI3K, and mTOR signaling. Through chemogenomic screening, we found that clinically relevant PI3K/mTOR inhibitors were able to inhibit coronavirus replication at nanomolar concentrations similar to direct-acting antivirals. This study lays the groundwork for identifying broad-acting, host-targeted therapies to reduce betacoronavirus replication that can be rapidly repurposed during future outbreaks and epidemics. The proteomics, phosphoproteomics, and MIB-MS datasets generated in this study are available in the Proteomics Identification Database (PRIDE) repository under project identifiers PXD040897 and PXD040901.

Published
2023
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17. A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies

Author

Dinnon, Kenneth H., primary, Leist, Sarah R., additional, Okuda, Kenichi, additional, Dang, Hong, additional, Fritch, Ethan J., additional, Gully, Kendra L., additional, De la Cruz, Gabriela, additional, Evangelista, Mia D., additional, Asakura, Takanori, additional, Gilmore, Rodney C., additional, Hawkins, Padraig, additional, Nakano, Satoko, additional, West, Ande, additional, Schäfer, Alexandra, additional, Gralinski, Lisa E., additional, Everman, Jamie L., additional, Sajuthi, Satria P., additional, Zweigart, Mark R., additional, Dong, Stephanie, additional, McBride, Jennifer, additional, Cooley, Michelle R., additional, Hines, Jesse B., additional, Love, Miriya K., additional, Groshong, Steve D., additional, VanSchoiack, Alison, additional, Phelan, Stefan J., additional, Liang, Yan, additional, Hether, Tyler, additional, Leon, Michael, additional, Zumwalt, Ross E., additional, Barton, Lisa M., additional, Duval, Eric J., additional, Mukhopadhyay, Sanjay, additional, Stroberg, Edana, additional, Borczuk, Alain, additional, Thorne, Leigh B., additional, Sakthivel, Muthu K., additional, Lee, Yueh Z., additional, Hagood, James S., additional, Mock, Jason R., additional, Seibold, Max A., additional, O’Neal, Wanda K., additional, Montgomery, Stephanie A., additional, Boucher, Richard C., additional, and Baric, Ralph S., additional

Published
2022
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18. Protective Efficacy of Rhesus Adenovirus COVID-19 Vaccines against Mouse-Adapted SARS-CoV-2

Author

Tostanoski, Lisa H., primary, Gralinski, Lisa E., additional, Martinez, David R., additional, Schaefer, Alexandra, additional, Mahrokhian, Shant H., additional, Li, Zhenfeng, additional, Nampanya, Felix, additional, Wan, Huahua, additional, Yu, Jingyou, additional, Chang, Aiquan, additional, Liu, Jinyan, additional, McMahan, Katherine, additional, Ventura, John D., additional, Dinnon, Kenneth H., additional, Leist, Sarah R., additional, Baric, Ralph S., additional, and Barouch, Dan H., additional

Published
2021
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19. Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection

Author

Geng, Qibin, primary, Tai, Wanbo, additional, Baxter, Victoria K., additional, Shi, Juan, additional, Wan, Yushun, additional, Zhang, Xiujuan, additional, Montgomery, Stephanie A., additional, Taft-Benz, Sharon A., additional, Anderson, Elizabeth J., additional, Knight, Audrey C., additional, Dinnon, Kenneth H., additional, Leist, Sarah R., additional, Baric, Ralph S., additional, Shang, Jian, additional, Hong, Sung-Wook, additional, Drelich, Aleksandra, additional, Tseng, Chien-Te K., additional, Jenkins, Marc, additional, Heise, Mark, additional, Du, Lanying, additional, and Li, Fang, additional

Published
2021
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20. COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge

Author

DiPiazza, Anthony T., primary, Leist, Sarah R., additional, Abiona, Olubukola M., additional, Moliva, Juan I., additional, Werner, Anne, additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Bock, Kevin W., additional, Phung, Emily, additional, Schäfer, Alexandra, additional, Dinnon, Kenneth H., additional, Chang, Lauren A., additional, Loomis, Rebecca J., additional, Boyoglu-Barnum, Seyhan, additional, Alvarado, Gabriela S., additional, Sullivan, Nancy J., additional, Edwards, Darin K., additional, Morabito, Kaitlyn M., additional, Mascola, John R., additional, Carfi, Andrea, additional, Corbett, Kizzmekia S., additional, Moore, Ian N., additional, Baric, Ralph S., additional, Graham, Barney S., additional, and Ruckwardt, Tracy J., additional

Published
2021
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21. SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

Author

Routhu, Nanda Kishore, primary, Cheedarla, Narayanaiah, additional, Bollimpelli, Venkata Satish, additional, Gangadhara, Sailaja, additional, Edara, Venkata Viswanadh, additional, Lai, Lilin, additional, Sahoo, Anusmita, additional, Shiferaw, Ayalnesh, additional, Styles, Tiffany M., additional, Floyd, Katharine, additional, Fischinger, Stephanie, additional, Atyeo, Caroline, additional, Shin, Sally A., additional, Gumber, Sanjeev, additional, Kirejczyk, Shannon, additional, Dinnon, Kenneth H., additional, Shi, Pei-Yong, additional, Menachery, Vineet D., additional, Tomai, Mark, additional, Fox, Christopher B., additional, Alter, Galit, additional, Vanderford, Thomas H., additional, Gralinski, Lisa, additional, Suthar, Mehul S., additional, and Amara, Rama Rao, additional

Published
2021
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23. Abstract P35: Targeting vimentin impacts multiple cellular processes, blocks the spike protein-ACE2-mediated pseudoviral infection in vitro and reduces the symptom and lung injury in aged mice with mouse-adapted SARS-CoV-2 infection in vivo

Author

Li, Zhizhen, primary, Wu, Jianping, additional, Yuan, Baoshi, additional, Dinnon, Kenneth, additional, Mo, Lian, additional, Zhou, Fei, additional, Dong, Yingying, additional, Gully, Kendra, additional, Baric, Ralph, additional, Graham, Rachel, additional, Xu, Ying, additional, and Chen, Ruihuan, additional

Published
2021
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24. Publisher Correction: A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures

Author

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
2021
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25. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo

Author

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

Published
2020
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26. A Newcastle Disease Virus (NDV) Expressing a Membrane-Anchored Spike as a Cost-Effective Inactivated SARS-CoV-2 Vaccine

Author

Sun, Weina, primary, McCroskery, Stephen, additional, Liu, Wen-Chun, additional, Leist, Sarah R., additional, Liu, Yonghong, additional, Albrecht, Randy A., additional, Slamanig, Stefan, additional, Oliva, Justine, additional, Amanat, Fatima, additional, Schäfer, Alexandra, additional, Dinnon, Kenneth H., additional, Innis, Bruce L., additional, García-Sastre, Adolfo, additional, Krammer, Florian, additional, Baric, Ralph S., additional, and Palese, Peter, additional

Published
2020
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27. Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as a live virus vaccine candidate

Author

Sun, Weina, primary, Leist, Sarah R., additional, McCroskery, Stephen, additional, Liu, Yonghong, additional, Slamanig, Stefan, additional, Oliva, Justine, additional, Amanat, Fatima, additional, Schäfer, Alexandra, additional, Dinnon, Kenneth H., additional, García-Sastre, Adolfo, additional, Krammer, Florian, additional, Baric, Ralph S., additional, and Palese, Peter, additional

Published
2020
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28. A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice

Author

Leist, Sarah R., primary, Dinnon, Kenneth H., additional, Schäfer, Alexandra, additional, Tse, Longping V., additional, Okuda, Kenichi, additional, Hou, Yixuan J., additional, West, Ande, additional, Edwards, Caitlin E., additional, Sanders, Wes, additional, Fritch, Ethan J., additional, Gully, Kendra L., additional, Scobey, Trevor, additional, Brown, Ariane J., additional, Sheahan, Timothy P., additional, Moorman, Nathaniel J., additional, Boucher, Richard C., additional, Gralinski, Lisa E., additional, Montgomery, Stephanie A., additional, and Baric, Ralph S., additional

Published
2020
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29. Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2

Author

Walls, Alexandra C., primary, Fiala, Brooke, additional, Schäfer, Alexandra, additional, Wrenn, Samuel, additional, Pham, Minh N., additional, Murphy, Michael, additional, Tse, Longping V., additional, Shehata, Laila, additional, O’Connor, Megan A., additional, Chen, Chengbo, additional, Navarro, Mary Jane, additional, Miranda, Marcos C., additional, Pettie, Deleah, additional, Ravichandran, Rashmi, additional, Kraft, John C., additional, Ogohara, Cassandra, additional, Palser, Anne, additional, Chalk, Sara, additional, Lee, E-Chiang, additional, Guerriero, Kathryn, additional, Kepl, Elizabeth, additional, Chow, Cameron M., additional, Sydeman, Claire, additional, Hodge, Edgar A., additional, Brown, Brieann, additional, Fuller, Jim T., additional, Dinnon, Kenneth H., additional, Gralinski, Lisa E., additional, Leist, Sarah R., additional, Gully, Kendra L., additional, Lewis, Thomas B., additional, Guttman, Miklos, additional, Chu, Helen Y., additional, Lee, Kelly K., additional, Fuller, Deborah H., additional, Baric, Ralph S., additional, Kellam, Paul, additional, Carter, Lauren, additional, Pepper, Marion, additional, Sheahan, Timothy P., additional, Veesler, David, additional, and King, Neil P., additional

Published
2020
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30. SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo

Author

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

Published
2020
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31. Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801

Author

Wahl, Angela, primary, Gralinski, Lisa, additional, Johnson, Claire, additional, Yao, Wenbo, additional, Kovarova, Martina, additional, Dinnon, Kenneth, additional, Liu, Hongwei, additional, Madden, Victoria, additional, Krzystek, Halina, additional, De, Chandrav, additional, White, Kristen, additional, Schäfer, Alexandra, additional, Zaman, Tanzila, additional, Leist, Sarah, additional, Grant, Paul, additional, Gully, Kendra, additional, Askin, Frederic, additional, Browne, Edward, additional, Jones, Corbin, additional, Pickles, Raymond, additional, Baric, Ralph, additional, and Garcia, J Victor, additional

Published
2020
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32. A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

Author

Sun, Weina, primary, McCroskery, Stephen, additional, Liu, Wen-Chun, additional, Leist, Sarah R., additional, Liu, Yonghong, additional, Albrecht, Randy A., additional, Slamanig, Stefan, additional, Oliva, Justine, additional, Amanat, Fatima, additional, Schaefer, Alexandra, additional, Dinnon, Kenneth H., additional, Innis, Bruce L., additional, Garcia-Sastre, Adolfo, additional, Krammer, Florian, additional, Baric, Ralph S., additional, and Palese, Peter, additional

Published
2020
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33. Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as vaccine candidate

Author

Sun, Weina, primary, Leist, Sarah R., additional, McCroskery, Stephen, additional, Liu, Yonghong, additional, Slamanig, Stefan, additional, Oliva, Justine, additional, Amanat, Fatima, additional, Schäfer, Alexandra, additional, Dinnon, Kenneth H., additional, García-Sastre, Adolfo, additional, Krammer, Florian, additional, Baric, Ralph S., additional, and Palese, Peter, additional

Published
2020
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34. Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice

Author

Pruijssers, Andrea J., primary, George, Amelia S., additional, Schäfer, Alexandra, additional, Leist, Sarah R., additional, Gralinksi, Lisa E., additional, Dinnon, Kenneth H., additional, Yount, Boyd L., additional, Agostini, Maria L., additional, Stevens, Laura J., additional, Chappell, James D., additional, Lu, Xiaotao, additional, Hughes, Tia M., additional, Gully, Kendra, additional, Martinez, David R., additional, Brown, Ariane J., additional, Graham, Rachel L., additional, Perry, Jason K., additional, Du Pont, Venice, additional, Pitts, Jared, additional, Ma, Bin, additional, Babusis, Darius, additional, Murakami, Eisuke, additional, Feng, Joy Y., additional, Bilello, John P., additional, Porter, Danielle P., additional, Cihlar, Tomas, additional, Baric, Ralph S., additional, Denison, Mark R., additional, and Sheahan, Timothy P., additional

Published
2020
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35. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

Author

Hou, Yixuan J., primary, Okuda, Kenichi, additional, Edwards, Caitlin E., additional, Martinez, David R., additional, Asakura, Takanori, additional, Dinnon, Kenneth H., additional, Kato, Takafumi, additional, Lee, Rhianna E., additional, Yount, Boyd L., additional, Mascenik, Teresa M., additional, Chen, Gang, additional, Olivier, Kenneth N., additional, Ghio, Andrew, additional, Tse, Longping V., additional, Leist, Sarah R., additional, Gralinski, Lisa E., additional, Schäfer, Alexandra, additional, Dang, Hong, additional, Gilmore, Rodney, additional, Nakano, Satoko, additional, Sun, Ling, additional, Fulcher, M. Leslie, additional, Livraghi-Butrico, Alessandra, additional, Nicely, Nathan I., additional, Cameron, Mark, additional, Cameron, Cheryl, additional, Kelvin, David J., additional, de Silva, Aravinda, additional, Margolis, David M., additional, Markmann, Alena, additional, Bartelt, Luther, additional, Zumwalt, Ross, additional, Martinez, Fernando J., additional, Salvatore, Steven P., additional, Borczuk, Alain, additional, Tata, Purushothama R., additional, Sontake, Vishwaraj, additional, Kimple, Adam, additional, Jaspers, Ilona, additional, O’Neal, Wanda K., additional, Randell, Scott H., additional, Boucher, Richard C., additional, and Baric, Ralph S., additional

Published
2020
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36. SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness

Author

Corbett, Kizzmekia S., primary, Edwards, Darin, additional, Leist, Sarah R., additional, Abiona, Olubukola M., additional, Boyoglu-Barnum, Seyhan, additional, Gillespie, Rebecca A., additional, Himansu, Sunny, additional, Schäfer, Alexandra, additional, Ziwawo, Cynthia T., additional, DiPiazza, Anthony T., additional, Dinnon, Kenneth H., additional, Elbashir, Sayda M., additional, Shaw, Christine A., additional, Woods, Angela, additional, Fritch, Ethan J., additional, Martinez, David R., additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Hutchinson, Geoffrey B., additional, Bahl, Kapil, additional, Garcia-Dominguez, Dario, additional, Ma, LingZhi, additional, Renzi, Isabella, additional, Kong, Wing-Pui, additional, Schmidt, Stephen D., additional, Wang, Lingshu, additional, Zhang, Yi, additional, Stevens, Laura J., additional, Phung, Emily, additional, Chang, Lauren A., additional, Loomis, Rebecca J., additional, Altaras, Nedim Emil, additional, Narayanan, Elisabeth, additional, Metkar, Mihir, additional, Presnyak, Vlad, additional, Liu, Catherine, additional, Louder, Mark K., additional, Shi, Wei, additional, Leung, Kwanyee, additional, Yang, Eun Sung, additional, West, Ande, additional, Gully, Kendra L., additional, Wang, Nianshuang, additional, Wrapp, Daniel, additional, Doria-Rose, Nicole A., additional, Stewart-Jones, Guillaume, additional, Bennett, Hamilton, additional, Nason, Martha C., additional, Ruckwardt, Tracy J., additional, McLellan, Jason S., additional, Denison, Mark R., additional, Chappell, James D., additional, Moore, Ian N., additional, Morabito, Kaitlyn M., additional, Mascola, John R., additional, Baric, Ralph S., additional, Carfi, Andrea, additional, and Graham, Barney S., additional

Published
2020
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37. A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures

Author

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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38. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice

Author

Sheahan, Timothy P., primary, Sims, Amy C., additional, Zhou, Shuntai, additional, Graham, Rachel L., additional, Pruijssers, Andrea J., additional, Agostini, Maria L., additional, Leist, Sarah R., additional, Schäfer, Alexandra, additional, Dinnon, Kenneth H., additional, Stevens, Laura J., additional, Chappell, James D., additional, Lu, Xiaotao, additional, Hughes, Tia M., additional, George, Amelia S., additional, Hill, Collin S., additional, Montgomery, Stephanie A., additional, Brown, Ariane J., additional, Bluemling, Gregory R., additional, Natchus, Michael G., additional, Saindane, Manohar, additional, Kolykhalov, Alexander A., additional, Painter, George, additional, Harcourt, Jennifer, additional, Tamin, Azaibi, additional, Thornburg, Natalie J., additional, Swanstrom, Ronald, additional, Denison, Mark R., additional, and Baric, Ralph S., additional

Published
2020
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39. Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice

Author

Pruijssers, Andrea J., primary, George, Amelia S., additional, Schäfer, Alexandra, additional, Leist, Sarah R., additional, Gralinksi, Lisa E., additional, Dinnon, Kenneth H., additional, Yount, Boyd L., additional, Agostini, Maria L., additional, Stevens, Laura J., additional, Chappell, James D., additional, Lu, Xiaotao, additional, Hughes, Tia M., additional, Gully, Kendra, additional, Martinez, David R., additional, Brown, Ariane J., additional, Graham, Rachel L., additional, Perry, Jason K., additional, Du Pont, Venice, additional, Pitts, Jared, additional, Ma, Bin, additional, Babusis, Darius, additional, Murakami, Eisuke, additional, Feng, Joy Y., additional, Bilello, John P., additional, Porter, Danielle P., additional, Cihlar, Tomas, additional, Baric, Ralph S., additional, Denison, Mark R., additional, and Sheahan, Timothy P., additional

Published
2020
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40. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus

Author

Sheahan, Timothy P., primary, Sims, Amy C., additional, Zhou, Shuntai, additional, Graham, Rachel L., additional, Hill, Collin S., additional, Leist, Sarah R., additional, Schäfer, Alexandra, additional, Dinnon, Kenneth H., additional, Montgomery, Stephanie A., additional, Agostini, Maria L., additional, Pruijssers, Andrea J., additional, Chapell, James D., additional, Brown, Ariane J., additional, Bluemling, Gregory R., additional, Natchus, Michael G., additional, Saindane, Manohar, additional, Kolykhalov, Alexander A., additional, Painter, George, additional, Harcourt, Jennifer, additional, Tamin, Azaibi, additional, Thornburg, Natalie J., additional, Swanstrom, Ronald, additional, Denison, Mark R., additional, and Baric, Ralph S., additional

Published
2020
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41. Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection

Author

Menachery, Vineet D., primary, Dinnon, Kenneth H., additional, Yount, Boyd L., additional, McAnarney, Eileen T., additional, Gralinski, Lisa E., additional, Hale, Andrew, additional, Graham, Rachel L., additional, Scobey, Trevor, additional, Anthony, Simon J., additional, Wang, Lingshu, additional, Graham, Barney, additional, Randell, Scott H., additional, Lipkin, W. Ian, additional, and Baric, Ralph S., additional

Published
2020
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42. Trypsin treatment unlocks barrier for zoonotic coronaviruses infection

Author

Menachery, Vineet D., primary, Dinnon, Kenneth H., additional, Yount, Boyd L., additional, McAnarney, Eileen T., additional, Gralinski, Lisa E., additional, Hale, Andrew, additional, Graham, Rachel L., additional, Scobey, Trevor, additional, Anthony, Simon J., additional, Wang, Lingshu, additional, Graham, Barney, additional, Randell, Scott H., additional, Lipkin, W. Ian, additional, and Baric, Ralph S., additional

Published
2019
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46. Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis

Author

Menachery, Vineet D., primary, Gralinski, Lisa E., additional, Mitchell, Hugh D., additional, Dinnon, Kenneth H., additional, Leist, Sarah R., additional, Yount, Boyd L., additional, Graham, Rachel L., additional, McAnarney, Eileen T., additional, Stratton, Kelly G., additional, Cockrell, Adam S., additional, Debbink, Kari, additional, Sims, Amy C., additional, Waters, Katrina M., additional, and Baric, Ralph S., additional

Published
2017
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47. MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

Author

Menachery, Vineet D., primary, Mitchell, Hugh D., additional, Cockrell, Adam S., additional, Gralinski, Lisa E., additional, Yount, Boyd L., additional, Graham, Rachel L., additional, McAnarney, Eileen T., additional, Douglas, Madeline G., additional, Scobey, Trevor, additional, Beall, Anne, additional, Dinnon, Kenneth, additional, Kocher, Jacob F., additional, Hale, Andrew E., additional, Stratton, Kelly G., additional, Waters, Katrina M., additional, and Baric, Ralph S., additional

Published
2017
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48. MERS-CoV NSP16 necessary for IFN resistance and viral pathogenesis

Author

Menachery, Vineet D., primary, Gralinski, Lisa E., additional, Mitchell, Hugh D., additional, Dinnon, Kenneth H., additional, Leist, Sarah R., additional, Yount, Boyd L., additional, Graham, Rachel L., additional, McAnarney, Eileen T., additional, Stratton, Kelly G., additional, Cockrell, Adam S., additional, Debbink, Kari, additional, Sims, Amy C., additional, Waters, Katrina M., additional, and Baric, Ralph S., additional

Published
2017
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50. Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity.

Author

Dinnon, Kenneth, Gallichotte, Emily, Fritch, Ethan, Menachery, Vineet, and Baric, Ralph

Subjects
*ZIKA virus
Abstract

Zika virus (ZIKV) is a mosquito-borne positive sense RNA virus. Recently, ZIKV emerged into the Western hemisphere as a human health threat, with severe disease associated with developmental and neurological complications. The structural envelope protein of ZIKV and other neurotropic flaviviruses contains an extended CD-loop relative to non-neurotropic flaviviruses, and has been shown to augment ZIKV stability and pathogenesis. Here we show that shortening the CD-loop in ZIKV attenuates the virus in mice, by reducing the ability to invade and replicate in the central nervous system. The CD-loop mutation was genetically stable following infection in mice, though secondary site mutations arise adjacent to the CD-loop. Importantly, while shortening of the CD-loop attenuates the virus, the CD-loop mutant maintains antigenicity in immunocompetent mice, eliciting an antibody response that similarly neutralizes both the mutant and wildtype ZIKV. These findings suggest that the extended CD-loop in ZIKV is a determinant of neurotropism and may be a target in live-attenuated vaccine design, for not only ZIKV, but for other neurotropic flaviviruses. [ABSTRACT FROM AUTHOR]

Published
2019
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