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- | ==== Link Dump ==== | ||
+ | ==== 2009 Activation of the SARS coronavirus spike protein ==== | ||
+ | {{ :: | ||
+ | Abstract | ||
+ | The coronavirus spike protein (S) plays a key role in the early steps of viral infection, with the S1 domain responsible for receptor binding and the S2 domain mediating membrane fusion. | ||
+ | |||
+ | In some cases, the S protein is proteolytically cleaved at the S1–S2 boundary. In the case of the severe acute respiratory syndrome coronavirus (SARS-CoV), it has been shown that virus entry requires the endosomal protease cathepsin L; however, it was also found that infection of SARS-CoV could be strongly induced by trypsin treatment. | ||
+ | |||
+ | Overall, in terms of how cleavage might activate membrane fusion, proteolytic processing of the SARS-CoV S protein remains unclear. Here, we identify a proteolytic cleavage site within the SARS-CoV S2 domain (S2′, R797). Mutation of R797 specifically inhibited trypsin-dependent fusion in both cell–cell fusion and pseudovirion entry assays. | ||
+ | |||
+ | We also introduced a furin cleavage site at both the S2′ cleavage site within S2 793-KPTKR-797 (S2′), as well as at the junction of S1 and S2. Introduction of a furin cleavage site at the S2′ position allowed trypsin-independent cell–cell fusion, which was strongly increased by the presence of a second furin cleavage site at the S1–S2 position. | ||
+ | |||
+ | Taken together, these data suggest a novel priming mechanism for a viral fusion protein, with a critical proteolytic cleavage event on the SARS-CoV S protein at position 797 (S2′), acting in concert with the S1–S2 cleavage site to mediate membrane fusion and virus infectivity. ((https:// | ||
+ | |||
+ | |||
+ | ==== SARS-CoV-2 ferritin nanoparticle vaccine ==== | ||
+ | |||
+ | A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates ((https:// | ||
+ | |||
+ | === Science Translational Medicine === | ||
+ | |||
+ | 16 Dec 2021 • First Release • DOI: 10.1126/ | ||
+ | |||
+ | Self-assembling protein nanoparticle vaccines offer the advantage of multivalent antigen presentation, | ||
+ | |||
+ | |||
+ | The prefusion-stabilized form of the spike protein is the basis for most major SARS-CoV-2 vaccine candidates (16, 17). Although a correlate of protection from COVID-19 has not been conclusively defined, there is mounting evidence that neutralizing, | ||
+ | |||
+ | The most potent neutralizing antibodies are directed against the spike protein receptor-binding domain (RBD), which mediates attachment to the primary host cell receptor, angiotensin converting enzyme (ACE2). Our prior assessment of a SARS-CoV-2 spike protein ferritin [[: | ||
+ | |||
+ | These data have provided a basis for evaluating SpFN immunogenicity and efficacy against viral replication and pathology in the airways and lungs of nonhuman primates (NHP), a standard model for preclinical evaluation of SARS-CoV-2 vaccines (21). | ||
+ | |||
+ | === Authors Info & Affiliations === ((https:// | ||
+ | |||
+ | M. Gordon Joyce* https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA. | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Hannah A. D. King https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. Military HIV Research Program, WRAIR, Silver Spring, MD 20910, USA. | ||
+ | Roles: Formal analysis, Visualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Ines Elakhal-Naouar https:// | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Diagnostics and Countermeasures Branch, WRAIR, Silver Spring, MD 20910, USA. | ||
+ | Roles: Formal analysis, Investigation, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Aslaa Ahmed https:// | ||
+ | Viral Diseases Branch, [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Kristina K. Peachman https:// | ||
+ | Diagnostics and Countermeasures Branch, [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Formal analysis, Investigation, | ||
+ | |||
+ | |||
+ | Camila Macedo Cincotta https:// | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Diagnostics and Countermeasures Branch, [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Investigation, | ||
+ | |||
+ | |||
+ | Caroline Subra https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. Military HIV Research Program, WRAIR, Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Rita E. Chen https:// | ||
+ | Department of Medicine, Washington University, St. Louis, MO 63130, USA. | ||
+ | Department of Pathology and Immunology, [[: | ||
+ | Roles: Formal analysis, Investigation, | ||
+ | |||
+ | |||
+ | Paul V. Thomas | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Wei-Hung Chen | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Formal analysis, Investigation, | ||
+ | |||
+ | |||
+ | Rajeshwer S. Sankhala | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Agnes Hajduczki | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Resources and Visualization. | ||
+ | |||
+ | |||
+ | Elizabeth J. Martinez https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Formal analysis, Investigation, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Caroline E. Peterson https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Investigation, | ||
+ | |||
+ | |||
+ | William C. Chang https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Investigation, | ||
+ | |||
+ | |||
+ | Misook Choe https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA. | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Role: Investigation. | ||
+ | |||
+ | |||
+ | Clayton Smith | ||
+ | Center for Molecular Microscopy, Center for Cancer Research, [[:National Cancer Institute]], | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Parker J. Lee https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA. | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Formal analysis and Investigation. | ||
+ | |||
+ | |||
+ | Jarrett A. Headley https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Funding acquisition and Project administration. View all articles by this author | ||
+ | |||
+ | |||
+ | Mekdi G. Taddese | ||
+ | [[:Emerging Infectious Diseases Branch]], Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Funding acquisition, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Hanne A. Elyard | ||
+ | [[: | ||
+ | Roles: Methodology, | ||
+ | |||
+ | |||
+ | Anthony Cook | ||
+ | [[: | ||
+ | Roles: Investigation, | ||
+ | |||
+ | |||
+ | Alexander Anderson https:// | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | [[:Oak Ridge Institute of Science and Education]], | ||
+ | Roles: Resources and Writing - review & editing. | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Kathryn McGuckin Wuertz https:// | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Data curation, Investigation, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Ming Dong | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA. | ||
+ | [[:Henry M. Jackson Foundation]] for the Advancement of Military Medicine, Bethesda, MD 20817, USA. | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Data curation, Investigation, | ||
+ | |||
+ | |||
+ | Isabella Swafford https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA. | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Role: Investigation. | ||
+ | |||
+ | |||
+ | James Brett Case https:// | ||
+ | Department of Medicine, [[: | ||
+ | Roles: Investigation and Validation. | ||
+ | |||
+ | |||
+ | Jeffrey R. Currier https:// | ||
+ | [[:Viral Diseases Branch]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Investigation, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Kerri G. Lal | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. Military HIV Research Program, WRAIR, Silver Spring, MD 20910, USA. | ||
+ | Roles: Formal analysis and Investigation. | ||
+ | |||
+ | |||
+ | Sebastian Molnar https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. Military HIV Research Program, WRAIR, Silver Spring, MD 20910, USA. | ||
+ | Roles: Data curation, Investigation, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | |||
+ | Manoj S. Nair https:// | ||
+ | [[:Diamond AIDS Research Center]], [[:Columbia University]] Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. | ||
+ | Roles: Investigation, | ||
+ | |||
+ | |||
+ | |||
+ | Vincent Dussupt https:// | ||
+ | Emerging Infectious Diseases Branch, [[:Walter Reed Army Institute of Research]] ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. Military HIV Research Program, WRAIR, Silver Spring, MD 20910, USA. | ||
+ | Roles: Investigation, | ||
+ | |||
+ | |||
+ | Sharon P. Daye | ||
+ | [[:Center for Infectious Diseases Research]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Xiankun Zeng https:// | ||
+ | Division of Pathology, [[:United States Army Medical Research Institute of Infectious Diseases]], Frederick, MD 21702, USA. Role: Investigation | ||
+ | |||
+ | |||
+ | Erica K. Barkei https:// | ||
+ | [[: | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Hilary M. Staples | ||
+ | Department of Virology and Immunology, [[:Texas Biomedical Research Institute]], | ||
+ | |||
+ | |||
+ | Kendra Alfson https:// | ||
+ | Department of Virology and Immunology, [[:Texas Biomedical Research Institute]], | ||
+ | Role: Investigation. View all articles by this author | ||
+ | |||
+ | |||
+ | Ricardo Carrion https:// | ||
+ | Department of Virology and Immunology, [[:Texas Biomedical Research Institute]], | ||
+ | Roles: Methodology, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Shelly J. Krebs https:// | ||
+ | Emerging Infectious Diseases Branch, [[:Walter Reed Army Institute of Research]] (WRAIR), Silver Spring, MD 20910, USA. | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Dominic Paquin-Proulx https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA. | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. Military HIV Research Program, [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Investigation and Writing - review & editing. | ||
+ | |||
+ | |||
+ | Nicos Karasavva https:// | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Diagnostics and Countermeasures Branch, [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Victoria R. Polonis | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Data curation, Investigation, | ||
+ | |||
+ | |||
+ | Linda L. Jagodzinski https:// | ||
+ | Diagnostics and Countermeasures Branch, [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Mihret F. Amare https:// | ||
+ | [[:Emerging Infectious Diseases Branch]], Walter Reed Army Institute of Research ([[: | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Sandhya Vasan https:// | ||
+ | Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA. | ||
+ | [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Paul T. Scott https:// | ||
+ | Emerging Infectious Diseases Branch, [[:Walter Reed Army Institute of Research]] ([[: | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Yaoxing Huang https:// | ||
+ | [[:Diamond AIDS Research Center]], [[:Columbia University]] Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. | ||
+ | Roles: Investigation, | ||
+ | |||
+ | |||
+ | David D. Ho https:// | ||
+ | [[:Diamond AIDS Research Center]], [[:Columbia University]] Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. | ||
+ | Roles: Formal analysis, Funding acquisition, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Natalia de Val https:// | ||
+ | Center for Molecular Microscopy, [[:Center for Cancer Research]], [[:National Cancer Institute]], | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Michael S. Diamond https:// | ||
+ | Department of Medicine, [[: | ||
+ | Department of Pathology and Immunology, Washington University, St. Louis, MO 63130, USA. | ||
+ | Department of Molecular Microbiology, | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Mark G. Lewis https:// | ||
+ | [[: | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Mangala Rao https:// | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Gary R. Matyas https:// | ||
+ | U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Investigation, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Gregory D. Gromowski https:// | ||
+ | Viral Diseases Branch, [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | |||
+ | |||
+ | Sheila A. Peel | ||
+ | [[: | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Nelson L. Michael https:// | ||
+ | Center for Infectious Diseases Research, [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | Roles: Conceptualization, | ||
+ | View all articles by this author | ||
+ | |||
+ | |||
+ | Diane L. Bolton https:// | ||
+ | Emerging Infectious Diseases Branch, [[:Walter Reed Army Institute of Research]] (WRAIR), Silver Spring, MD 20910, USA. [[:Henry M. Jackson Foundation for the Advancement of Military Medicine]], Bethesda, MD 20817, USA. U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | |||
+ | Roles: Conceptualization, | ||
+ | |||
+ | Kayvon Modjarrad - kayvon.modjarrad.civ@mail.mil | ||
+ | Emerging Infectious Diseases Branch, [[:Walter Reed Army Institute of Research]] [[:WRAIR]], Silver Spring, MD 20910, USA. | ||
+ | |||
+ | Roles: Conceptualization, | ||
+ | |||
+ | Funding Information - U.S. [[: | ||
+ | Notes - Corresponding author. Email: kayvon.modjarrad.civ@mail.mil (K.M.); gjoyce@eidresearch.org (M.G.J.) | ||
+ | |||
+ | ==== Link Dump ==== | ||
+ | {{ :: | ||
Spike protein clotting | Spike protein clotting | ||