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2. Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro

Author

Radoshitzky, Sheli R., Iversen, Patrick, Lu, Xianghan, Zou, Jing, Kaptein, Suzanne J. F., Stuthman, Kelly S., Van Tongeren, Sean A., Steffens, Jesse, Gong, Ruoyu, Truong, Hoa, Sapre, Annapurna A., Yang, Huiling, Xie, Xiaodong, Chia, Jia Jun, Song, Zhijuan J., Leventhal, Stacey M., Chan, Josolyn, Shornikov, Alex, Zhang, Xin, Cowfer, David, Yu, Helen, Warren, Travis, Cihlar, Tomas, Porter, Danielle P., Neyts, Johan, Shi, Pei-Yong, Wells, Jay, Bilello, John P., and Feng, Joy Y.

Published
2023
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4. Identification of NK Cell Subpopulations That Differentiate HIV-Infected Subject Cohorts with Diverse Levels of Virus Control

Author

Pohlmeyer, Christopher W, Gonzalez, Veronica D, Irrinki, Alivelu, Ramirez, Ricardo N, Li, Li, Mulato, Andrew, Murry, Jeffrey P, Arvey, Aaron, Hoh, Rebecca, Deeks, Steven G, Kukolj, George, Cihlar, Tomas, Pflanz, Stefan, Nolan, Garry P, and Min-Oo, Gundula

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, Clinical Research, HIV/AIDS, 2.1 Biological and endogenous factors, Infection, CD11b Antigen, CD56 Antigen, CD57 Antigens, CD8-Positive T-Lymphocytes, Cell Line, Tumor, DNA, Viral, HIV Infections, HIV-1, Humans, K562 Cells, Killer Cells, Natural, NK Cell Lectin-Like Receptor Subfamily B, Receptors, IgG, Viremia, elite controller, machine learning, mass cytometry, human immunodeficiency virus, natural killer cells, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

HIV infection is controlled immunologically in a small subset of infected individuals without antiretroviral therapy (ART), though the mechanism of control is unclear. CD8+ T cells are a critical component of HIV control in many immunological controllers. NK cells are also believed to have a role in controlling HIV infection, though their role is less well characterized. We used mass cytometry to simultaneously measure the levels of expression of 24 surface markers on peripheral NK cells from HIV-infected subjects with various degrees of HIV natural control; we then used machine learning to identify NK cell subpopulations that differentiate HIV controllers from noncontrollers. Using CITRUS (cluster identification, characterization, and regression), we identified 3 NK cell subpopulations that differentiated subjects with chronic HIV viremia (viremic noncontrollers [VNC]) from individuals with undetectable HIV viremia without ART (elite controllers [EC]). In a parallel approach, we identified 11 NK cell subpopulations that differentiated HIV-infected subject groups using k-means clustering after dimensionality reduction by t-neighbor stochastic neighbor embedding (tSNE) or linear discriminant analysis (LDA). Among these additional 11 subpopulations, the frequencies of 5 correlated with HIV DNA levels; importantly, significance was retained in 2 subpopulations in analyses that included only cohorts without detectable viremia. By comparing the surface marker expression patterns of all identified subpopulations, we revealed that the CD11b+ CD57- CD161+ Siglec-7+ subpopulation of CD56dim CD16+ NK cells are more abundant in EC and HIV-negative controls than in VNC and that the frequency of these cells correlated with HIV DNA levels. We hypothesize that this population may have a role in immunological control of HIV infection.IMPORTANCE HIV infection results in the establishment of a stable reservoir of latently infected cells; ART is usually required to keep viral replication under control and disease progression at bay, though a small subset of HIV-infected subjects can control HIV infection without ART through immunological mechanisms. In this study, we sought to identify subpopulations of NK cells that may be involved in the natural immunological control of HIV infection. We used mass cytometry to measure surface marker expression on peripheral NK cells. Using two distinct semisupervised machine learning approaches, we identified a CD11b+ CD57- CD161+ Siglec-7+ subpopulation of CD56dim CD16+ NK cells that differentiates HIV controllers from noncontrollers. These cells can be sorted out for future functional studies to assess their potential role in the immunological control of HIV infection.

Published
2019

5. Long-acting capsid inhibitor protects macaques from repeat SHIV challenges

Author

Vidal, Samuel J., Bekerman, Elena, Hansen, Derek, Lu, Bing, Wang, Kelly, Mwangi, Judy, Rowe, William, Campigotto, Federico, Zheng, Jim, Kato, Darryl, Chandrashekar, Abishek, Barrett, Julia, Patel, Shivani, Wan, Huahua, Anioke, Tochi, Mercado, Noe B., Nkolola, Joseph P., Ferguson, Melissa J., Rinaldi, William J., Callebaut, Christian, Blair, Wade, Cihlar, Tomas, Geleziunas, Romas, Yant, Stephen R., and Barouch, Dan H.

Published
2022
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8. 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., George, Amelia S., Schäfer, Alexandra, Leist, Sarah R., Gralinksi, Lisa E., Dinnon, Kenneth H., III, Yount, Boyd L., Agostini, Maria L., Stevens, Laura J., Chappell, James D., Lu, Xiaotao, Hughes, Tia M., Gully, Kendra, Martinez, David R., Brown, Ariane J., Graham, Rachel L., Perry, Jason K., Du Pont, Venice, Pitts, Jared, Ma, Bin, Babusis, Darius, Murakami, Eisuke, Feng, Joy Y., Bilello, John P., Porter, Danielle P., Cihlar, Tomas, Baric, Ralph S., Denison, Mark R., and Sheahan, Timothy P.

Published
2020
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9. Preclinical characterization of a non-peptidomimetic HIV protease inhibitor with improved metabolic stability

Author

Mulato, Andrew, primary, Lansdon, Eric, additional, Aoyama, Ron, additional, Voigt, Johannes, additional, Lee, Michael, additional, Liclican, Albert, additional, Lee, Gary, additional, Singer, Eric, additional, Stafford, Brian, additional, Gong, Ruoyu, additional, Murray, Bernard, additional, Chan, Julie, additional, Lee, Johnny, additional, Xu, Yili, additional, Ahmadyar, Shekeba, additional, Gonzalez, Ana, additional, Cho, Aesop, additional, Stepan, George J., additional, Schmitz, Uli, additional, Schultz, Brian, additional, Marchand, Bruno, additional, Brumshtein, Boris, additional, Wang, Ruth, additional, Yu, Helen, additional, Cihlar, Tomas, additional, Xu, Lianhong, additional, and Yant, Stephen R., additional

Published
2024
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10. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2

Author

Williamson, Brandi N., Feldmann, Friederike, Schwarz, Benjamin, Meade-White, Kimberly, Porter, Danielle P., Schulz, Jonathan, van Doremalen, Neeltje, Leighton, Ian, Yinda, Claude Kwe, Pérez-Pérez, Lizzette, Okumura, Atsushi, Lovaglio, Jamie, Hanley, Patrick W., Saturday, Greg, Bosio, Catharine M., Anzick, Sarah, Barbian, Kent, Cihlar, Tomas, Martens, Craig, Scott, Dana P., Munster, Vincent J., and de Wit, Emmie

Published
2020
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11. Clinical targeting of HIV capsid protein with a long-acting small molecule

Author

Link, John O., Rhee, Martin S., Tse, Winston C., Zheng, Jim, Somoza, John R., Rowe, William, Begley, Rebecca, Chiu, Anna, Mulato, Andrew, Hansen, Derek, Singer, Eric, Tsai, Luong K., Bam, Rujuta A., Chou, Chien-Hung, Canales, Eda, Brizgys, Gediminas, Zhang, Jennifer R., Li, Jiayao, Graupe, Michael, Morganelli, Philip, Liu, Qi, Wu, Qiaoyin, Halcomb, Randall L., Saito, Roland D., Schroeder, Scott D., Lazerwith, Scott E., Bondy, Steven, Jin, Debi, Hung, Magdeleine, Novikov, Nikolai, Liu, Xiaohong, Villaseñor, Armando G., Cannizzaro, Carina E., Hu, Eric Y., Anderson, Robert L., Appleby, Todd C., Lu, Bing, Mwangi, Judy, Liclican, Albert, Niedziela-Majka, Anita, Papalia, Giuseppe A., Wong, Melanie H., Leavitt, Stephanie A., Xu, Yili, Koditek, David, Stepan, George J., Yu, Helen, Pagratis, Nikos, Clancy, Sheila, Ahmadyar, Shekeba, Cai, Terrence Z., Sellers, Scott, Wolckenhauer, Scott A., Ling, John, Callebaut, Christian, Margot, Nicolas, Ram, Renee R., Liu, Ya-Pei, Hyland, Rob, Sinclair, Gary I., Ruane, Peter J., Crofoot, Gordon E., McDonald, Cheryl K., Brainard, Diana M., Lad, Latesh, Swaminathan, Swami, Sundquist, Wesley I., Sakowicz, Roman, Chester, Anne E., Lee, William E., Daar, Eric S., Yant, Stephen R., and Cihlar, Tomas

Published
2020
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12. Antiviral Efficacy of a Respiratory Syncytial Virus (RSV) Fusion Inhibitor in a Bovine Model of RSV Infection

Author

Jordan, Robert, Shao, Matt, Mackman, Richard L, Perron, Michel, Cihlar, Tomas, Lewis, Sandy A, Eisenberg, Eugene J, Carey, Anne, Strickley, Robert G, Chien, Jason W, Anderson, Mark L, McEligot, Heather A, Behrens, Nicole E, and Gershwin, Laurel J

Subjects
Infectious Diseases, Pediatric, Pneumonia, Pneumonia & Influenza, Lung, Respiratory, Infection, Animals, Antiviral Agents, Bronchiolitis, Cattle, Cattle Diseases, Cell Line, Cell Membrane, Double-Blind Method, Humans, Indazoles, Male, Pyrazoles, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Bovine, Respiratory Syncytial Virus, Human, Sulfonamides, Viral Load, Microbiology, Medical Microbiology, Pharmacology and Pharmaceutical Sciences
Abstract

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Effective treatment for RSV infection is a significant unmet medical need. While new RSV therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human RSV, making it difficult to evaluate new disease interventions. Experimental infection of Holstein calves with bovine RSV (bRSV) causes a severe respiratory infection that is similar to human RSV infection, providing a relevant model for testing novel therapeutic agents. In this model, viral load is readily detected in nasal secretions by quantitative real-time PCR (qRT-PCR), and cumulative symptom scoring together with histopathology evaluations of infected tissue allow for the assessment of disease severity. The bovine RSV model was used to evaluate the antiviral activity of an RSV fusion inhibitor, GS1, which blocks virus entry by inhibiting the fusion of the viral envelope with the host cell membrane. The efficacy of GS1, a close structural analog of GS-5806 that is being developed to treat RSV infection in humans was evaluated in two randomized, blind, placebo-controlled studies in bRSV-infected calves. Intravenous administration of GS1 at 4 mg/kg of body weight/day for 7 days starting 24 h or 72 h postinoculation provided clear therapeutic benefit by reducing the viral load, disease symptom score, respiration rate, and lung pathology associated with bRSV infection. These data support the use of the bovine RSV model for evaluation of experimental therapeutics for treatment of RSV.

Published
2015

16. A pharmacogenetic candidate gene study of tenofovir-associated Fanconi syndrome

Author

Dahlin, Amber, Wittwer, Matthias, de la Cruz, Melanie, Woo, Jonathan M, Bam, Rujuta, Scharen-Guivel, Valeska, Flaherty, John, Ray, Adrian S, Cihlar, Tomas, Gupta, Samir K, and Giacomini, Kathleen M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Patient Safety, Infectious Diseases, Pediatric, Kidney Disease, 2.1 Biological and endogenous factors, Renal and urogenital, Adenine, Alleles, Anti-HIV Agents, Biomarkers, Pharmacological, Case-Control Studies, Fanconi Syndrome, Genetic Association Studies, HEK293 Cells, HIV Infections, HIV-1, Humans, Multidrug Resistance-Associated Protein 2, Organophosphonates, Pharmacogenetics, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Tenofovir, Fanconi syndrome, HIV, pharmacogenetics, tenofovir, transporter, Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

BackgroundTenofovir disoproxil fumarate (TDF) is a widely used antiretroviral agent with favorable efficacy, safety, and tolerability profiles. However, renal adverse events, including the rare Fanconi syndrome (FS), may occur in a small subset of patients treated for HIV infections.ObjectivesThe aim of this study was to identify genetic variants that may be associated with TDF-associated FS (TDF-FS).MethodsDNA samples collected from 19 cases with TDF-FS and 36 matched controls were sequenced, and genetic association studies were conducted on eight candidate genes: ATP-binding cassette (ABC) transporters ABCC2 (MRP2) and ABCC4 (MRP4), solute carrier family members SLC22A6 (OAT1) and SLC22A8 (OAT3), adenylate kinases 2 (AK2) and 4 (AK4), chloride transporter CIC-5 CLCN5, and Lowe syndrome protein OCRL. The functional effects of a single nucleotide polymorphism (SNP) predicted to alter the transport of tenofovir were then investigated in cells expressing an identified variant of ABCC4.ResultsThe case group showed a trend toward a higher proportion of rare alleles. Six SNPs in ABCC2 (three SNPs), ABCC4 (one SNP), and OCRL (two SNPs) were associated with TDF-FS case status; however, this association did not remain significant after correction for multiple testing. Six SNPs, present in OCRL (four SNPs) and ABCC2 (two SNPs), were significantly associated with increased serum creatinine levels in the cases, and this association remained significant after multiple test correction (P < 2 × 10). One synonymous SNP in ABCC2 (rs8187707, P = 2.10 × 10, β = -73.3 ml/min/1.73 m(2)) was also significantly associated with the decreased estimated glomerular filtration rate of creatinine among cases. However, these results were driven by rare SNPs present in a small number of severely affected cases. Finally, a previously uncharacterized, nonsynonymous SNP, rs11568694, that was predicted to alter MRP4 function had no significant effect on tenofovir cellular accumulation in vitro.ConclusionAlthough no single predictive genetic marker for the development of TDF-FS was identified, the findings from our study suggest that rare variants in multiple genes involved in the renal handling of tenofovir, and/or renal cell homeostasis, may be associated with increased susceptibility to TDF-FS.

Published
2015

18. A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model

Author

Yant, Stephen R., Mulato, Andrew, Hansen, Derek, Tse, Winston C., Niedziela-Majka, Anita, Zhang, Jennifer R., Stepan, George J., Jin, Debi, Wong, Melanie H., Perreira, Jill M., Singer, Eric, Papalia, Giuseppe A., Hu, Eric Y., Zheng, Jim, Lu, Bing, Schroeder, Scott D., Chou, Kevin, Ahmadyar, Shekeba, Liclican, Albert, Yu, Helen, Novikov, Nikolai, Paoli, Eric, Gonik, Daniel, Ram, Renee R., Hung, Magdeleine, McDougall, William M., Brass, Abraham L., Sundquist, Wesley I., Cihlar, Tomas, and Link, John O.

Published
2019
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20. Characterization of the Cynomolgus Macaque Model of Marburg Virus Disease and Assessment of Timing for Therapeutic Treatment Testing

Author

Zumbrun, Elizabeth E., primary, Garvey, Carly B., additional, Wells, Jay B., additional, Lynn, Ginger C., additional, Van Tongeren, Sean, additional, Steffens, Jesse T., additional, Wetzel, Kelly S., additional, Gomba, Laura M., additional, O’Brien, Kristan A., additional, Rossi, Franco D., additional, Zeng, Xiankun, additional, Lee, Eric D., additional, Raymond, Jo Lynne W., additional, Hoffman, Diana A., additional, Jay, Alexandra N., additional, Brown, Elizabeth S., additional, Kallgren, Paul A., additional, Norris, Sarah L., additional, Cantey-Kiser, Jean, additional, Kudiya, Humza, additional, Arthur, Chris, additional, Blair, Christiana, additional, Babusis, Darius, additional, Chu, Victor C., additional, Singh, Bali, additional, Bannister, Roy, additional, Porter, Danielle P., additional, Cihlar, Tomas, additional, and Dye, John M., additional

Published
2023
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21. 539. Efficacy in Multiple SARS-CoV-2 Animal Models Supports Phase 3 Dose Selection for Obeldesivir

Author

Pitts, Jared, primary, Babusis, Darius, additional, Humeniuk, Rita, additional, Martinez, David, additional, Cox, Robert M, additional, Schäfer, Alexandra, additional, Riola, Nicholas C, additional, Feng, Joy, additional, Du Pont, Venice, additional, Anoshchenko, Olena, additional, Vermillion, Meghan, additional, Abdelghany, Mazin, additional, Hyland, Robert H, additional, Girish, Sandhya, additional, Sheahan, Timothy P, additional, Plemper, Richard K, additional, Baric, Ralph S, additional, Cihlar, Tomas, additional, Llewellyn, Joe, additional, Winter, Helen, additional, Bannister, Roy, additional, Subramanian, Raju, additional, Mackman, Richard L, additional, and Bilello, John P, additional

Published
2023
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23. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

Author

Sheahan, Timothy P., Sims, Amy C., Leist, Sarah R., Schäfer, Alexandra, Won, John, Brown, Ariane J., Montgomery, Stephanie A., Hogg, Alison, Babusis, Darius, Clarke, Michael O., Spahn, Jamie E., Bauer, Laura, Sellers, Scott, Porter, Danielle, Feng, Joy Y., Cihlar, Tomas, Jordan, Robert, Denison, Mark R., and Baric, Ralph S.

Published
2020
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25. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys

Author

Warren, Travis K., Jordan, Robert, Lo, Michael K., Ray, Adrian S., Mackman, Richard L., Soloveva, Veronica, Siegel, Dustin, Perron, Michel, Bannister, Roy, Hui, Hon C., Larson, Nate, Strickley, Robert, Wells, Jay, Stuthman, Kelly S., Van Tongeren, Sean A., Garza, Nicole L., Donnelly, Ginger, Shurtleff, Amy C., Retterer, Cary J., Gharaibeh, Dima, Zamani, Rouzbeh, Kenny, Tara, Eaton, Brett P., Grimes, Elizabeth, Welch, Lisa S., Gomba, Laura, Wilhelmsen, Catherine L., Nichols, Donald K., Nuss, Jonathan E., Nagle, Elyse R., Kugelman, Jeffrey R., Palacios, Gustavo, Doerffler, Edward, Neville, Sean, Carra, Ernest, Clarke, Michael O., Zhang, Lijun, Lew, Willard, Ross, Bruce, Wang, Queenie, Chun, Kwon, Wolfe, Lydia, Babusis, Darius, Park, Yeojin, Stray, Kirsten M., Trancheva, Iva, Feng, Joy Y., Barauskas, Ona, Xu, Yili, Wong, Pamela, Braun, Molly R., Flint, Mike, McMullan, Laura K., Chen, Shan-Shan, Fearns, Rachel, Swaminathan, Swami, Mayers, Douglas L., Spiropoulou, Christina F., Lee, William A., Nichol, Stuart T., Cihlar, Tomas, and Bavari, Sina

Published
2016
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26. The Nucleoside/Nucleotide Analogs Tenofovir and Emtricitabine Are Inactive against SARS-CoV-2

Author

Feng, Joy Y., primary, Du Pont, Venice, additional, Babusis, Darius, additional, Gordon, Calvin J., additional, Tchesnokov, Egor P., additional, Perry, Jason K., additional, Duong, Vincent, additional, Vijjapurapu, Arya, additional, Zhao, Xiaofeng, additional, Chan, Julie, additional, Cohen, Cal, additional, Juneja, Kavita, additional, Cihlar, Tomas, additional, Götte, Matthias, additional, and Bilello, John P., additional

Published
2022
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27. Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants

Author

Pitts, Jared, primary, Li, Jiani, additional, Perry, Jason K., additional, Du Pont, Venice, additional, Riola, Nicholas, additional, Rodriguez, Lauren, additional, Lu, Xianghan, additional, Kurhade, Chaitanya, additional, Xie, Xuping, additional, Camus, Gregory, additional, Manhas, Savrina, additional, Martin, Ross, additional, Shi, Pei-Yong, additional, Cihlar, Tomas, additional, Porter, Danielle P., additional, Mo, Hongmei, additional, Maiorova, Evguenia, additional, and Bilello, John P., additional

Published
2022
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33. Long-acting capsid inhibitor protects macaques from repeat SHIV challenges

Author

Vidal, Samuel J., primary, Bekerman, Elena, additional, Hansen, Derek, additional, Lu, Bing, additional, Wang, Kelly, additional, Mwangi, Judy, additional, Rowe, William, additional, Campigotto, Federico, additional, Zheng, Jim, additional, Kato, Darryl, additional, Chandrashekar, Abishek, additional, Barrett, Julia, additional, Patel, Shivani, additional, Wan, Huahua, additional, Anioke, Tochi, additional, Mercado, Noe B., additional, Nkolola, Joseph P., additional, Ferguson, Melissa J., additional, Rinaldi, William J., additional, Callebaut, Christian, additional, Blair, Wade, additional, Cihlar, Tomas, additional, Geleziunas, Romas, additional, Yant, Stephen R., additional, and Barouch, Dan H., additional

Published
2021
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37. Off-Target In Vitro Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent

Author

Xu, Yili, primary, Barauskas, Ona, additional, Kim, Cynthia, additional, Babusis, Darius, additional, Murakami, Eisuke, additional, Kornyeyev, Dmytro, additional, Lee, Gary, additional, Stepan, George, additional, Perron, Michel, additional, Bannister, Roy, additional, Schultz, Brian E., additional, Sakowicz, Roman, additional, Porter, Danielle, additional, Cihlar, Tomas, additional, and Feng, Joy Y., additional

Published
2021
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39. Characterization of Ebola Virus Disease (EVD) in Rhesus Monkeys for Development of EVD Therapeutics

Author

Warren, Travis, primary, Zumbrun, Elizabeth, additional, Weidner, Jessica M., additional, Gomba, Laura, additional, Rossi, Franco, additional, Bannister, Roy, additional, Tarrant, Jacqueline, additional, Reed, Matthew, additional, Lee, Eric, additional, Raymond, Jo Lynne, additional, Wells, Jay, additional, Shamblin, Joshua, additional, Wetzel, Kelly, additional, Donnelly, Ginger, additional, Van Tongeren, Sean, additional, Lackemeyer, Nicole, additional, Steffens, Jesse, additional, Kimmel, Adrienne, additional, Garvey, Carly, additional, Bloomfield, Holly, additional, Blair, Christiana, additional, Singh, Bali, additional, Bavari, Sina, additional, Cihlar, Tomas, additional, and Porter, Danielle, additional

Published
2020
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40. 539. GS-CA2: A Novel, Potent, and Selective First-In-class Inhibitor of HIV-1 Capsid Function Displays Nonclinical Pharmacokinetics Supporting Long-Acting Potential in Humans

Author

Zheng, Jim, primary, Yant, Stephen R, additional, Ahmadyar, Shekeba, additional, Chan, Tiffany Y, additional, Chiu, Anna, additional, Cihlar, Tomas, additional, Link, John O, additional, Lu, Bing, additional, Mwangi, Judy, additional, Rowe, William, additional, Schroeder, Scott D, additional, Stepan, George J, additional, Wang, Kelly Wei, additional, Subramanian, Raju, additional, and Tse, Winston C, additional

Published
2018
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41. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease

Author

Agostini, Maria L., primary, Andres, Erica L., additional, Sims, Amy C., additional, Graham, Rachel L., additional, Sheahan, Timothy P., additional, Lu, Xiaotao, additional, Smith, Everett Clinton, additional, Case, James Brett, additional, Feng, Joy Y., additional, Jordan, Robert, additional, Ray, Adrian S., additional, Cihlar, Tomas, additional, Siegel, Dustin, additional, Mackman, Richard L., additional, Clarke, Michael O., additional, Baric, Ralph S., additional, and Denison, Mark R., additional

Published
2018
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43. GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses

Author

Lo, Michael K., primary, Jordan, Robert, additional, Arvey, Aaron, additional, Sudhamsu, Jawahar, additional, Shrivastava-Ranjan, Punya, additional, Hotard, Anne L., additional, Flint, Mike, additional, McMullan, Laura K., additional, Siegel, Dustin, additional, Clarke, Michael O., additional, Mackman, Richard L., additional, Hui, Hon C., additional, Perron, Michel, additional, Ray, Adrian S., additional, Cihlar, Tomas, additional, Nichol, Stuart T., additional, and Spiropoulou, Christina F., additional

Published
2017
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44. Off-Target In VitroProfiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent

Author

Xu, Yili, Barauskas, Ona, Kim, Cynthia, Babusis, Darius, Murakami, Eisuke, Kornyeyev, Dmytro, Lee, Gary, Stepan, George, Perron, Michel, Bannister, Roy, Schultz, Brian E., Sakowicz, Roman, Porter, Danielle, Cihlar, Tomas, and Feng, Joy Y.

Abstract

Remdesivir (RDV, GS-5734), the first FDA-approved antiviral for the treatment of COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. It is intracellularly metabolized into the active triphosphate form, which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases.

Published
2021
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46. Broad-spectrum Investigational Agent GS-5734 for the Treatment of Ebola, MERS Coronavirus and Other Pathogenic Viral Infections with High Outbreak Potential

Author

Jordan, Robert, primary, Hogg, Alison, additional, Warren, Travis, additional, De Wit, Emmie, additional, Sheahan, Timothy, additional, Lo, Michael, additional, Soloveva, Veronica, additional, Weidner, Jessica, additional, Gomba, Laura, additional, Feldmann, Friederike, additional, Cronin, Jacqueline, additional, Sims, Amy, additional, Cockrell, Adam, additional, Feng, Joy, additional, Trantcheva, Iva, additional, Babusis, Darius, additional, Porter-Poulin, Danielle, additional, Bannister, Roy, additional, Mackman, Richard, additional, Siegel, Dustin, additional, Ray, Adrian, additional, Denison, Mark, additional, Spiropoulou, Christina, additional, Nichol, Stuart, additional, Cihlar, Tomas, additional, Baric, Ralph, additional, Feldmann, Heinrich, additional, and Bavari, Sina, additional

Published
2017
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47. Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile

Author

Tsiang, Manuel, primary, Jones, Gregg S., additional, Goldsmith, Joshua, additional, Mulato, Andrew, additional, Hansen, Derek, additional, Kan, Elaine, additional, Tsai, Luong, additional, Bam, Rujuta A., additional, Stepan, George, additional, Stray, Kirsten M., additional, Niedziela-Majka, Anita, additional, Yant, Stephen R., additional, Yu, Helen, additional, Kukolj, George, additional, Cihlar, Tomas, additional, Lazerwith, Scott E., additional, White, Kirsten L., additional, and Jin, Haolun, additional

Published
2016
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48. GS-5806 Inhibits a Broad Range of Respiratory Syncytial Virus Clinical Isolates by Blocking the Virus-Cell Fusion Process

Author

Perron, Michel, primary, Stray, Kirsten, additional, Kinkade, April, additional, Theodore, Dorothy, additional, Lee, Gary, additional, Eisenberg, Eugene, additional, Sangi, Michael, additional, Gilbert, Brian E., additional, Jordan, Robert, additional, Piedra, Pedro A., additional, Toms, Geoffery L., additional, Mackman, Richard, additional, and Cihlar, Tomas, additional

Published
2016
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