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54. Correction for Piepenbrink et al., “Highly Cross-Reactive and Protective Influenza A Virus H3N2 Hemagglutinin- and Neuraminidase-Specific Human Monoclonal Antibodies”

Author

Piepenbrink, Michael, primary, Oladunni, Fatai, additional, Nogales, Aitor, additional, Khalil, Ahmed M., additional, Fitzgerald, Theresa, additional, Hilimire, Thomas A., additional, Basu, Madhubanti, additional, Fucile, Christopher, additional, Topham, David J., additional, Rosenberg, Alexander F., additional, Martinez-Sobrido, Luis, additional, and Kobie, James J., additional

Published
2024
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56. Inhibition of mRNA nuclear export promotes SARS-CoV-2 pathogenesis.

Author

Mei, Menghan, Cupic, Anastasija, Miorin, Lisa, Chengjin Ye, Cagatay, Tolga, Ke Zhang, Patel, Komal, Wilson, Natalie, McDonald, W. Hayes, Crossland, Nicholas A., Ming Lo, Rutkowska, Magdalena, Aslam, Sadaf, Mena, Ignacio, Martinez-Sobrido, Luis, Yi Ren, García-Sastre, Adolfo, and Fontoura, Beatriz M. A.

Subjects
SARS-CoV-2, MESSENGER RNA
Abstract

The nonstructural protein 1 (Nsp1) of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a virulence factor that targets multiple cellular pathways to inhibit host gene expression and antiviral response. However, the underlying mechanisms of the various Nsp1-mediated functions and their contributions to SARS-CoV-2 virulence remain unclear. Among the targets of Nsp1 is the mRNA (messenger ribonucleic acid) export receptor NXF1-NXT1, which mediates nuclear export of mRNAs from the nucleus to the cytoplasm. Based on Nsp1 crystal structure, we generated mutants on Nsp1 surfaces and identified an acidic N-terminal patch that is critical for interaction with NXF1-NXT1. Photoactivatable Nsp1 probe reveals the RNA Recognition Motif (RRM) domain of NXF1 as an Nsp1 N-terminal binding site. By mutating the Nsp1 N-terminal acidic patch, we identified a separation-of-function mutant of Nsp1 that retains its translation inhibitory function but substantially loses its interaction with NXF1 and reverts Nsp1-mediated mRNA export inhibition. We then generated a recombinant (r)SARS-CoV-2 mutant on the Nsp1 N-terminal acidic patch and found that this surface is key to promote NXF1 binding and inhibition of host mRNA nuclear export, viral replication, and pathogenicity in vivo. Thus, these findings provide a mechanistic understanding of Nsp1-mediated mRNA export inhibition and establish the importance of this pathway in the virulence of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Published
2024
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59. Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4+ T Cells in Aging

Author

Headley, Colwyn A., primary, Gautam, Shalini, additional, Olmo‐Fontanez, Angelica, additional, Garcia‐Vilanova, Andreu, additional, Dwivedi, Varun, additional, Akhter, Anwari, additional, Schami, Alyssa, additional, Chiem, Kevin, additional, Ault, Russell, additional, Zhang, Hao, additional, Cai, Hong, additional, Whigham, Alison, additional, Delgado, Jennifer, additional, Hicks, Amberlee, additional, Tsao, Philip S., additional, Gelfond, Jonathan, additional, Martinez‐Sobrido, Luis, additional, Wang, Yufeng, additional, Torrelles, Jordi B., additional, and Turner, Joanne, additional

Published
2023
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60. SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling

Author

Otter, Clayton J, primary, Bracci, Nicole, additional, Parenti, Nicholas A, additional, Ye, Chengjin, additional, Li Hui, Tan, additional, Asthana, Abhishek, additional, Pfannenstiel, Jessica J, additional, Jackson, Nathaniel, additional, Fehr, Anthony R, additional, Silverman, Robert H, additional, Cohen, Noam A, additional, Martinez-Sobrido, Luis, additional, and Weiss, Susan R, additional

Published
2023
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61. New Advances on Zika Virus Research.

Author

Martinez-Sobrido, Luis and Almazan Toral, Fernando

Subjects
Aedes aegypti, African-lineage, Asian lineage, Asian-lineage, Bacterial artificial chromosome, Bayesian analyses, ELISA, EQA, FSS13025, Full-length cDNA infectious clones, IgA, IgG avidity tests, MR766, NHP, NS1 protein, NS2A protein, NS5, Non-human primates, QCMD, RNA-seq, TLR7/8, Tet-inducible, ZIKV, ZIKV-associated neurologic disorders, ZIKV-host interactions, Zika, Zika virus, Zika virus (ZIKV), Ziks virus, anti-viral immunity, antiviral, antiviral compounds, antiviral responses, antivirals, apoptosis, arbovirus, assay standardization, astrocytomas, bacterial artificial chromosome, blood-retinal barrier, boolean logic-processing nucleic acid probes, cell surface receptors, chimeric viruses, clinical trials, congenital Zika syndrome, cross-reactions, cryptic promoter silencing, cytopathic effects, dengue virus, dengue viruses, detoxification and immune system responses, diagnosis, dsRNA, eIF4A, emerging arbovirus, external quality assessment, eye, fetal infection, flavivirus, flaviviruses, full-length molecular clone, gene expression, genetic variability, heme-oxygenase 1, hepatocytes, host genetic variation, host-directed antivirals, human brain glial cells, immune response, indirect immunofluorescence, infection, infectious RNA, infectious cDNA, infectious clone, innate response, insecticide resistance, isothermal nucleic acid amplification, laboratory preparedness, microRNAs, microcephaly, microglia cells, microsphere immunoassay, molecular diagnostics, monoclonal antibodies, mosquito, mosquito surveillance, mosquito-borne flavivirus, multiplex nucleic acid detection, mutagenesis, natural history, neural cells, neural progenitor cells, neuroinflammation, neurons, neuropathogenesis, nucleic acid computation, nucleic acid strand exchange, ocular, optimised, outbreak control, placenta cells, plaque reduction neutralization test, plasmid toxicity, point-of-care diagnostics, polymerase chain reaction, prM-E proteins, pregnancy, prostate, replication, replicon, reporter virus, research models and tools, reverse genetics, rhesus macaques, secondary infections, serology, sexual transmission, siRNA, silvestrol, subgenomic replicon, testes, testicular cells, testis, therapeutics, therapy, type I IFN antagonist, vaccines, validated, viral counteraction, viral evolution, viral fitness, viral genetic variation, viral pathogenesis, viral pathogenicity, viral permissiveness, viral persistence, viral replication, viral survival, virus attachment, virus like particles, zika virus
Abstract

Summary: Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that historically has been associated with mild febrile illness. However, the recent outbreaks in Brazil in 2015 and its rapid spread throughout South and Central America and the Caribbean, together with its association with severe neurological disorders-including fetal microcephaly and Guillain-Barré syndrome in adults-have changed the historic perspective of ZIKV. Currently, ZIKV is considered an important public health concern that has the potential to affect millions of people worldwide. The significance of ZIKV in human health and the lack of approved vaccines and/or antiviral drugs to combat ZIKV infection have triggered a global effort to develop effective countermeasures to prevent and/or treat ZIKV infection. In this Special Issue of Viruses, we have assembled a collection of 32 research and review articles that cover the more recent advances on ZIKV molecular biology, replication and transmission, virus-host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and viral diagnosis.

63. The immunological potency and therapeutic potential of a prototype dual vaccine against influenza and Alzheimer's disease

Author

Davtyan, Hayk, Ghochikyan, Anahit, Cadagan, Richard, Zamarin, Dmitriy, Petrushina, Irina, Movsesyan, Nina, Martinez-Sobrido, Luis, Albrecht, Randy A, García-Sastre, Adolfo, and Agadjanyan, Michael G

Abstract

Abstract Background Numerous pre-clinical studies and clinical trials demonstrated that induction of antibodies to the β-amyloid peptide of 42 residues (Aβ42) elicits therapeutic effects in Alzheimer's disease (AD). However, an active vaccination strategy based on full length Aβ42 is currently hampered by elicitation of T cell pathological autoreactivity. We attempt to improve vaccine efficacy by creating a novel chimeric flu vaccine expressing the small immunodominant B cell epitope of Aβ42. We hypothesized that in elderly people with pre-existing memory Th cells specific to influenza this dual vaccine will simultaneously boost anti-influenza immunity and induce production of therapeutically active anti-Aβ antibodies. Methods Plasmid-based reverse genetics system was used for the rescue of recombinant influenza virus containing immunodominant B cell epitopes of Aβ42 (Aβ1-7/10). Results Two chimeric flu viruses expressing either 7 or 10 aa of Aβ42 (flu-Aβ1-7 or flu-Aβ1-10) were generated and tested in mice as conventional inactivated vaccines. We demonstrated that this dual vaccine induced therapeutically potent anti-Aβ antibodies and anti-influenza antibodies in mice. Conclusion We suggest that this strategy might be beneficial for treatment of AD patients as well as for prevention of development of AD pathology in pre-symptomatic individuals while concurrently boosting immunity against influenza.

Published
2011

65. SARS‐CoV‐2 Protein Nanoparticle Vaccines Formed In Situ From Lyophilized Lipids

Author

Jiao, Yang, primary, Huang, Wei‐Chiao, additional, Chiem, Kevin, additional, Song, Yiting, additional, Sun, Jingyu, additional, Chothe, Shubhada K., additional, Zhou, Shiqi, additional, Luo, Yuan, additional, Mabrouk, Moustafa T., additional, Ortega, Joaquin, additional, Kuchipudi, Suresh V., additional, Martinez‐Sobrido, Luis, additional, and Lovell, Jonathan F, additional

Published
2023
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67. A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern

Author

Xu, Jiayu, primary, Zhang, Yuexiu, additional, Qu, Panke, additional, Shamseldin, Mohamed M., additional, Yoo, Sung J., additional, Misny, Jack, additional, Thongpan, Ilada, additional, KC, Mahesh, additional, Hall, Jesse M., additional, Evans, John P., additional, Eltobgy, Mostafa, additional, Lu, Mijia, additional, Ye, Chengjin, additional, Chamblee, Michelle, additional, Liang, Xueya, additional, Martinez-Sobrido, Luis, additional, Amer, Amal O., additional, Yount, Jacob S., additional, Boyaka, Prosper N., additional, Peeples, Mark E., additional, Liu, Shan-Lu, additional, Dubey, Purnima, additional, and Li, Jianrong, additional

Published
2023
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68. Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5

Author

Imbiakha, Brian, primary, Ezzatpour, Shahrzad, additional, Buchholz, David W., additional, Sahler, Julie, additional, Ye, Chengjin, additional, Olarte-Castillo, Ximena A., additional, Zou, Anna, additional, Kwas, Cole, additional, O’Hare, Katelyn, additional, Choi, Annette, additional, Adeleke, Richard Ayomide, additional, Khomandiak, Solomiia, additional, Goodman, Laura, additional, Jager, Mason C., additional, Whittaker, Gary R., additional, Martinez-Sobrido, Luis, additional, August, Avery, additional, and Aguilar, Hector C., additional

Published
2023
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70. Highly Cross-Reactive and Protective Influenza A Virus H3N2 Hemagglutinin- and Neuraminidase-Specific Human Monoclonal Antibodies

Author

Piepenbrink, Michael, primary, Oladunni, Fatai, additional, Nogales, Aitor, additional, Khalil, Ahmed M., additional, Fitzgerald, Theresa, additional, Basu, Madhubanti, additional, Fucile, Christopher, additional, Topham, David J., additional, Rosenberg, Alexander F., additional, Martinez-Sobrido, Luis, additional, and Kobie, James J., additional

Published
2023
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72. Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice

Author

Oladunni, Fatai S., Park, Jun-Gyu, Pino, Paula A., Gonzalez, Olga, Akhter, Anwari, Allué-Guardia, Anna, Olmo-Fontánez, Angélica, Gautam, Shalini, Garcia-Vilanova, Andreu, Ye, Chengjin, Chiem, Kevin, Headley, Colwyn, Dwivedi, Varun, Parodi, Laura M., Alfson, Kendra J., Staples, Hilary M., Schami, Alyssa, Garcia, Juan I., Whigham, Alison, Platt, II, Roy Neal, Gazi, Michal, Martinez, Jesse, Chuba, Colin, Earley, Stephanie, Rodriguez, Oscar H., Mdaki, Stephanie Davis, Kavelish, Katrina N., Escalona, Renee, Hallam, Cory R. A., Christie, Corbett, Patterson, Jean L., Anderson, Tim J. C., Carrion, Jr, Ricardo, Dick, Jr, Edward J., Hall-Ursone, Shannan, Schlesinger, Larry S., Alvarez, Xavier, Kaushal, Deepak, Giavedoni, Luis D., Turner, Joanne, Martinez-Sobrido, Luis, and Torrelles, Jordi B.

Published
2020
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74. New Advances on Zika Virus Research

Author

Martinez-Sobrido, Luis and Almazan Toral, Fernando

Abstract

Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that historically has been associated with mild febrile illness. However, the recent outbreaks in Brazil in 2015 and its rapid spread throughout South and Central America and the Caribbean, together with its association with severe neurological disorders—including fetal microcephaly and Guillain-Barré syndrome in adults—have changed the historic perspective of ZIKV. Currently, ZIKV is considered an important public health concern that has the potential to affect millions of people worldwide. The significance of ZIKV in human health and the lack of approved vaccines and/or antiviral drugs to combat ZIKV infection have triggered a global effort to develop effective countermeasures to prevent and/or treat ZIKV infection. In this Special Issue of Viruses, we have assembled a collection of 32 research and review articles that cover the more recent advances on ZIKV molecular biology, replication and transmission, virus–host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and viral diagnosis.

Published
2019

75. Influenza A virus replicates productively in primary human kidney cells and induces factors and mechanisms related to regulated cell death and renal pathology observed in virusinfected patients.

Author

Koch, Benjamin, Shehata, Mahmoud, Müller-Ruttloff, Christin, Gouda, Shady A., Wetzstein, Nils, Patyna, Sammy, Scholz, Anica, Schmid, Tobias, Dietrich, Ursula, Münch, Christian, Ziebuhr, John, Geiger, Helmut, Martinez-Sobrido, Luis, Baer, Patrick C., Mostafa, Ahmed, and Pleschka, Stephan

Subjects
LUNGS, INFLUENZA A virus, KIDNEYS, CELL death, INFLUENZA viruses, ADULT respiratory distress syndrome, ACUTE kidney failure
Abstract

Introduction: Influenza A virus (IAV) infection can cause the often-lethal acute respiratory distress syndrome (ARDS) of the lung. Concomitantly, acute kidney injury (AKI) is frequently noticed during IAV infection, correlating with an increased mortality. The aim of this study was to elucidate the interaction of IAV with human kidney cells and, thereby, to assess the mechanisms underlying IAV-mediated AKI. Methods: To investigate IAV effects on nephron cells we performed infectivity assays with human IAV, as well as with human isolates of either low or highly pathogenic avian IAV. Also, transcriptome and proteome analysis of IAV-infected primary human distal tubular kidney cells (DTC) was performed. Furthermore, the DTC transcriptome was compared to existing transcriptomic data from IAV-infected lung and trachea cells. Results: We demonstrate productive replication of all tested IAV strains on primary and immortalized nephron cells. Comparison of our transcriptome and proteome analysis of H1N1-type IAV-infected human primary distal tubular cells (DTC) with existing data from H1N1-type IAV-infected lung and primary trachea cells revealed enrichment of specific factors responsible for regulated cell death in primary DTC, which could be targeted by specific inhibitors. Discussion: IAV not only infects, but also productively replicates on different human nephron cells. Importantly, multi-omics analysis revealed regulated cell death as potential contributing factor for the clinically observed kidney pathology in influenza. [ABSTRACT FROM AUTHOR]

Published
2024
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76. Editorial for SARS-CoV-2 and COVID-19 Topical Collection.

Author

Martinez-Sobrido, Luis and Almazán, Fernando

Subjects
*SARS-CoV-2, *MONOCLONAL antibodies, *VIRAL antibodies, *SARS-CoV-2 Delta variant, *SARS-CoV-2 Omicron variant, *COVID-19
Abstract

This document is a collection of research articles focused on the study of SARS-CoV-2, the virus responsible for COVID-19. The articles cover a wide range of topics, including the molecular biology of the virus, its transmission and replication, interactions with the host, pathogenesis, epidemiology, and the development of vaccines and antiviral treatments. The goal of the collection is to provide up-to-date insights into SARS-CoV-2 and COVID-19, stimulating further research to improve prevention and treatment strategies. [Extracted from the article]

Published
2024
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78. Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4+ T Cells in Aging.

Author

Headley, Colwyn A., Gautam, Shalini, Olmo‐Fontanez, Angelica, Garcia‐Vilanova, Andreu, Dwivedi, Varun, Akhter, Anwari, Schami, Alyssa, Chiem, Kevin, Ault, Russell, Zhang, Hao, Cai, Hong, Whigham, Alison, Delgado, Jennifer, Hicks, Amberlee, Tsao, Philip S., Gelfond, Jonathan, Martinez‐Sobrido, Luis, Wang, Yufeng, Torrelles, Jordi B., and Turner, Joanne

Subjects
CELLULAR aging, T cells, AEROBIC metabolism, MYCOBACTERIAL diseases, MITOCHONDRIA, MYCOBACTERIUM tuberculosis, CD4 antigen, IMMUNOSENESCENCE
Abstract

Mitochondrial dysfunction alters cellular metabolism, increases tissue oxidative stress, and may be principal to the dysregulated signaling and function of CD4+ T lymphocytes in the elderly. In this proof of principle study, it is investigated whether the transfer of functional mitochondria into CD4+ T cells that are isolated from old mice (aged CD4+ T cells), can abrogate aging‐associated mitochondrial dysfunction, and improve the aged CD4+ T cell functionality. The results show that the delivery of exogenous mitochondria to aged non‐activated CD4+ T cells led to significant mitochondrial proteome alterations highlighted by improved aerobic metabolism and decreased cellular mitoROS. Additionally, mito‐transferred aged CD4+ T cells showed improvements in activation‐induced TCR‐signaling kinetics displaying markers of activation (CD25), increased IL‐2 production, enhanced proliferation ex vivo. Importantly, immune deficient mouse models (RAG‐KO) showed that adoptive transfer of mito‐transferred naive aged CD4+ T cells, protected recipient mice from influenza A and Mycobacterium tuberculosis infections. These findings support mitochondria as targets of therapeutic intervention in aging. [ABSTRACT FROM AUTHOR]

Published
2024
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81. A new tractable method for generating human alveolar macrophage-like cells in vitro to study lung inflammatory processes and diseases

Author

Pahari, Susanta, primary, Arnett, Eusondia, additional, Simper, Jan, additional, Azad, Abul, additional, Guerrero-Arguero, Israel, additional, Ye, Chengjin, additional, Zhang, Hao, additional, Cai, Hong, additional, Wang, Yufeng, additional, Lai, Zhao, additional, Jarvis, Natalie, additional, Lumbreras, Miranda, additional, Maselli, Diego Jose, additional, Peters, Jay, additional, Torrelles, Jordi B., additional, Martinez-Sobrido, Luis, additional, and Schlesinger, Larry S., additional

Published
2023
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82. Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models

Author

Lorenzo, María M., primary, Marín-López, Alejandro, additional, Chiem, Kevin, additional, Jimenez-Cabello, Luis, additional, Ullah, Irfan, additional, Utrilla-Trigo, Sergio, additional, Calvo-Pinilla, Eva, additional, Lorenzo, Gema, additional, Moreno, Sandra, additional, Ye, Chengjin, additional, Park, Jun-Gyu, additional, Matía, Alejandro, additional, Brun, Alejandro, additional, Sánchez-Puig, Juana M., additional, Nogales, Aitor, additional, Mothes, Walther, additional, Uchil, Pradeep D., additional, Kumar, Priti, additional, Ortego, Javier, additional, Fikrig, Erol, additional, Martinez-Sobrido, Luis, additional, and Blasco, Rafael, additional

Published
2023
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83. Immunization with Recombinant Accessory Protein-Deficient SARS-CoV-2 Protects against Lethal Challenge and Viral Transmission

Author

Ye, Chengjin, primary, Park, Jun-Gyu, additional, Chiem, Kevin, additional, Dravid, Piyush, additional, Allué-Guardia, Anna, additional, Garcia-Vilanova, Andreu, additional, Pino Tamayo, Paula, additional, Shivanna, Vinay, additional, Kapoor, Amit, additional, Walter, Mark R., additional, Kobie, James J., additional, Plemper, Richard K., additional, Torrelles, Jordi B., additional, and Martinez-Sobrido, Luis, additional

Published
2023
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84. Vaccinia Virus Strain Mva Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models

Author

Lorenzo, María M, primary, Marín-López, Alejandro, additional, Chiem, Kevin, additional, Jimenez-Cabello, Luis, additional, Ullah, Irfan, additional, Utrilla-Trigo, Sergio, additional, Calvo-Pinilla, Eva, additional, Lorenzo, Gema, additional, Moreno, Sandra, additional, Ye, Chengjin, additional, Park, Jun-Gyu, additional, Matía, Alejandro, additional, Brun, Alejandro, additional, Sánchez-Puig, Juana M, additional, Nogales, Aitor, additional, Mothes, Walther, additional, Uchil, Pradeep D, additional, Kumar, Priti, additional, Ortego, Javier, additional, Fikrig, Erol, additional, Martinez-Sobrido, Luis, additional, and Blasco, Rafael, additional

Published
2023
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85. Mitigation of SARS-CoV-2 by Using Transition Metal Nanozeolites and Quaternary Ammonium Compounds as Antiviral Agents in Suspensions and Soft Fabric Materials

Author

Guerrero-Arguero, Israel, primary, Khan, Siddiqur Rahman, additional, Henry, Brandon M, additional, Garcia-Vilanova, Andreu, additional, Chiem, Kevin, additional, Ye, Chengjin, additional, Shrestha, Sweta, additional, Knight, Deborah, additional, Cristner, Mark, additional, Hill, Shauna, additional, Waldman, W James, additional, Dutta, Prabir K, additional, Torrelles, Jordi B, additional, Martinez-Sobrido, Luis, additional, and Nagy, Amber M, additional

Published
2023
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91. A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo.

Author

Taha, Taha, Taha, Taha, Suryawanshi, Rahul, Chen, Irene, Correy, Galen, McCavitt-Malvido, Maria, OLeary, Patrick, Jogalekar, Manasi, Diolaiti, Morgan, Kimmerly, Gabriella, Tsou, Chia-Lin, Gascon, Ronnie, Montano, Mauricio, Martinez-Sobrido, Luis, Krogan, Nevan, Ashworth, Alan, Fraser, James, Ott, Melanie, Taha, Taha, Taha, Taha, Suryawanshi, Rahul, Chen, Irene, Correy, Galen, McCavitt-Malvido, Maria, OLeary, Patrick, Jogalekar, Manasi, Diolaiti, Morgan, Kimmerly, Gabriella, Tsou, Chia-Lin, Gascon, Ronnie, Montano, Mauricio, Martinez-Sobrido, Luis, Krogan, Nevan, Ashworth, Alan, Fraser, James, and Ott, Melanie

Abstract

Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the role of Mac1 catalytic activity in viral replication, we generated recombinant viruses and replicons encoding a catalytically inactive NSP3 Mac1 domain by mutating a critical asparagine in the active site. While substitution to alanine (N40A) reduced catalytic activity by ~10-fold, mutations to aspartic acid (N40D) reduced activity by ~100-fold relative to wild-type. Importantly, the N40A mutation rendered Mac1 unstable in vitro and lowered expression levels in bacterial and mammalian cells. When incorporated into SARS-CoV-2 molecular clones, the N40D mutant only modestly affected viral fitness in immortalized cell lines, but reduced viral replication in human airway organoids by 10-fold. In mice, the N40D mutant replicated at >1000-fold lower levels compared to the wild-type virus while inducing a robust interferon response; all animals infected with the mutant virus survived infection. Our data validate the critical role of SARS-CoV-2 NSP3 Mac1 catalytic activity in viral replication and as a promising therapeutic target to develop antivirals.

Published
2023

92. Antivirals against monkeypox infections

Author

Chiem, Kevin, primary, Nogales, Aitor, additional, Lorenzo, Maria M., additional, Morales Vasquez, Desarey, additional, Xiang, Yan, additional, Gupta, Yogesh, additional, Blasco, Rafael, additional, de la Torre, Juan C, additional, and Martinez-Sobrido, Luis, additional

Published
2023
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94. Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses

Author

Silva, Rui P, primary, Huang, Yimin, primary, Nguyen, Annalee W, primary, Hsieh, Ching-Lin, additional, Olaluwoye, Oladimeji S, additional, Kaoud, Tamer S, additional, Wilen, Rebecca E, additional, Qerqez, Ahlam N, additional, Park, Jun-Gyu, additional, Khalil, Ahmed M, additional, Azouz, Laura R, additional, Le, Kevin C, additional, Bohanon, Amanda L, additional, DiVenere, Andrea M, additional, Liu, Yutong, additional, Lee, Alison G, additional, Amengor, Dzifa A, additional, Shoemaker, Sophie R, additional, Costello, Shawn M, additional, Padlan, Eduardo A, additional, Marqusee, Susan, additional, Martinez-Sobrido, Luis, additional, Dalby, Kevin N, additional, D'Arcy, Sheena, additional, McLellan, Jason S, additional, and Maynard, Jennifer A, additional

Published
2023
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96. Author Correction: Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets

Author

Singh, Dhiraj Kumar, Singh, Bindu, Ganatra, Shashank R., Gazi, Michal, Cole, Journey, Thippeshappa, Rajesh, Alfson, Kendra J., Clemmons, Elizabeth, Gonzalez, Olga, Escobedo, Ruby, Lee, Tae-Hyung, Chatterjee, Ayan, Goez-Gazi, Yenny, Sharan, Riti, Gough, Maya, Alvarez, Cynthia, Blakley, Alyssa, Ferdin, Justin, Bartley, Carmen, Staples, Hilary, Parodi, Laura, Callery, Jessica, Mannino, Amanda, Klaffke, Benjamin, Escareno, Priscilla, Platt, II, Roy N., Hodara, Vida, Scordo, Julia, Gautam, Shalini, Vilanova, Andreu G., Olmo-Fontanez, Angelica, Schami, Alyssa, Oyejide, Adelekan, Ajithdoss, Dharani K., Copin, Richard, Baum, Alina, Kyratsous, Christos, Alvarez, Xavier, Ahmed, Mushtaq, Rosa, Bruce, Goodroe, Anna, Dutton, John, Hall-Ursone, Shannan, Frost, Patrice A., Voges, Andra K., Ross, Corinna N., Sayers, Ken, Chen, Christopher, Hallam, Cory, Khader, Shabaana A., Mitreva, Makedonka, Anderson, Timothy J. C., Martinez-Sobrido, Luis, Patterson, Jean L., Turner, Joanne, Torrelles, Jordi B., Dick, Jr, Edward J., Brasky, Kathleen, Schlesinger, Larry S., Giavedoni, Luis D., Carrion, Jr, Ricardo, and Kaushal, Deepak

Published
2021
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