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--- spike_protein [2021/11/10 01:43]
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 ===== Spike Protein =====
-What is a spike protein. Function of spike protein. Spike in other coronaviruses. Discuss past implications of spike in pathologies.
+What is a spike protein. Function of spike protein. Spike in other [[coronaviruses]]. Discuss past implications of spike in pathologies.
-=====Spike Protein of SARS-CoV-2
+=====SARS-CoV-2 Spike Protein=====
-Mention ACE2 affinity relative to SARS spike protein. Specific characteristics including those which point to lab origin. Specific and detail ACE2 binding information.
+Mention [[ACE2]] affinity relative to SARS spike protein. Specific characteristics including those which point to a [[origins of sars-cov-2|lab origin]]. Specific and detail [[ACE2]] binding information.
-Explain spike protein as a target for antibodies and value in vaccine manufacturing.
+Explain spike protein as a target for [[antibodies]] and value in [[COVID-19_vaccines|vaccine]] manufacturing.
-COVID-19 SPIKE PROTEIN PATHOLOGIES
+====Proposed Mechanisms of SARS-CoV-2 Spike Protein Pathology====
-Detail damage in relation to ACE2 down-regulation
+Detail effects of [[ACE2]] down-regulation and subsequent impact on [[RAAS]]. Detail role of [[Angiotensin 2]] in inflammation, clotting, angiogenesis, etc.
+[[AGE/RAGE]] connection with Ang 2 pathology.
+"In addition to eliciting an immune response that suppresses the viral entry, the spike protein produced by the COVID-19 vaccines may also affect the host cells, possibly triggering adverse events.((Suzuki, Y. J., & Gychka, S. G. (2021). //SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Host Cells: Implications for Possible Consequences of COVID-19 Vaccines.// Vaccines, 9(1), 36. https://doi.org/10.3390/vaccines9010036))
+==== Spike Protein SARS-CoV-2 ====
+A Possible Role for Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination
+William J. Murphy, Ph.D., and Dan L. Longo, M.D.
-==== Link Dump ====
+https://www.nejm.org/doi/full/10.1056/NEJMcibr2113694
+==== 2009 Activation of the SARS coronavirus spike protein ====
+{{ ::sars_spike_protein_activation_study.png?400|}}
+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://web.archive.org/web/20220427040816/https://www.pnas.org/doi/10.1073/pnas.0809524106))
+==== SARS-CoV-2 ferritin nanoparticle vaccine ====
+A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates ((https://web.archive.org/web/20211216192220/https://www.science.org/doi/10.1126/scitranslmed.abi5735))
+=== Science Translational Medicine ===
+Dec 2021 • First Release • DOI: 10.1126/scitranslmed.abi5735
+Self-assembling protein nanoparticle vaccines offer the advantage of multivalent antigen presentation, a property previously shown to augment immunogenicity over monovalent immunogens (5–7). Ferritin is a naturally occurring, ubiquitous, iron-carrying protein that self-oligomerizes into a 24-unit spherical particle (8). The three-fold axis symmetry of the resulting polymer makes it conducive to conjugation and antigen display of trimeric glycoproteins, such as [[:SARS-CoV-2]] spike protein. Ferritin has been evaluated as a vaccine platform for several pathogens (9–11), most notably influenza, for which it has demonstrated immune potency and breadth (12, 13). As such, ferritin vaccines have advanced to phase 1 clinical trials as a strategy to target multiple influenza strains (14, 15).
+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, and some fraction of non-neutralizing, antibodies against spike protein are necessary, if not sufficient, to confer protective immunity (18, 19).
+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 [[:nanoparticle]] (SpFN) vaccine candidate, co-formulated with a [[:liposomal adjuvant]], has demonstrated potent immunogenicity and protection against SARS-CoV-2 infection in mouse models (20).
+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://www.science.org/doi/10.1126/scitranslmed.abi5735))
+M. Gordon Joyce* https://orcid.org/0000-0002-6808-7232 kayvon.modjarrad.civ@mail.mil
+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, Data curation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, and Writing - review & editing.
+View all articles by this author
+Hannah A. D. King https://orcid.org/0000-0002-7575-198X
+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: Formal analysis, Visualization, and Writing - review & editing.
+View all articles by this author
+Ines Elakhal-Naouar https://orcid.org/0000-0001-6811-6534
+[[: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, Validation, Visualization, and Writing - review & editing.
+View all articles by this author
+Aslaa Ahmed https://orcid.org/0000-0003-3093-4982
+Viral Diseases Branch, [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Validation, and Visualization.  View all articles by this author
+Kristina K. Peachman https://orcid.org/0000-0001-8568-1439
+Diagnostics and Countermeasures Branch, [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Formal analysis, Investigation, Supervision, Validation, Visualization, Writing - original draft, and Writing - review & editing. View all articles by this author
+Camila Macedo Cincotta https://orcid.org/0000-0003-1495-1133
+[[: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, Project administration, Visualization, Writing - original draft, and Writing - review & editing.  View all articles by this author
+Caroline Subra https://orcid.org/0000-0001-5272-0972
+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, Investigation, Methodology, Resources, Validation, Visualization, and Writing - original draft.  View all articles by this author
+Rita E. Chen https://orcid.org/0000-0002-5100-7750
+Department of Medicine, Washington University, St. Louis, MO 63130, USA.
+Department of Pathology and Immunology, [[:Washington University St. Louis]], MO 63130, USA.
+Roles: Formal analysis, Investigation, and Validation.  View all articles by this author
+Paul V. Thomas
+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, Resources, Visualization, Writing - original draft, and Writing - review & editing.  View all articles by this author
+Wei-Hung Chen
+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, Investigation, Methodology, Validation, Visualization, Writing - original draft, and Writing - review & editing.  View all articles by this author
+Rajeshwer S. Sankhala
+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, Formal analysis, Investigation, Methodology, Project administration, Resources, Validation, Visualization, Writing - original draft, and Writing - review & editing.
+View all articles by this author
+Agnes Hajduczki
+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: Resources and Visualization.  View all articles by this author
+Elizabeth J. Martinez https://orcid.org/0000-0002-7755-7056
+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, Investigation, Resources, Visualization, and Writing - review & editing.
+View all articles by this author
+Caroline E. Peterson https://orcid.org/0000-0002-6087-7301
+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: Investigation, Resources, and Visualization.  View all articles by this author
+William C. Chang https://orcid.org/0000-0003-4967-6426
+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: Investigation, Resources, and Writing - review & editing.  View all articles by this author
+Misook Choe https://orcid.org/0000-0003-0243-5203
+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.  View all articles by this author
+Clayton Smith
+Center for Molecular Microscopy, Center for Cancer Research, [[:National Cancer Institute]], [[:National Institutes of Health]], Frederick, MD 21702, USA.
+Roles: Conceptualization, Data curation, Investigation, Resources, and Validation.
+View all articles by this author
+Parker J. Lee https://orcid.org/0000-0001-9601-8165
+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.  View all articles by this author
+Jarrett A. Headley https://orcid.org/0000-0001-5809-5485
+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: Funding acquisition and Project administration. View all articles by this author
+Mekdi G. Taddese
+[[: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: Funding acquisition, Project administration, and Writing - review & editing.
+View all articles by this author
+Hanne A. Elyard
+[[:Bioqual]], Rockville, MD 20850, USA.
+Roles: Methodology, Resources, and Validation.  View all articles by this author
+Anthony Cook
+[[:Bioqual]], Rockville, MD 20850, USA.
+Roles: Investigation, Methodology, and Resources. View all articles by this author
+Alexander Anderson https://orcid.org/0000-0002-0000-7734
+U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA.
+[[:Oak Ridge Institute of Science and Education]], Oak Ridge, TN 37830, USA.
+Roles: Resources and Writing - review & editing.
+View all articles by this author
+Kathryn McGuckin Wuertz https://orcid.org/0000-0003-2658-6284
+U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Data curation, Investigation, Validation, and Writing - review & editing.
+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, and Resources.  View all articles by this author
+Isabella Swafford https://orcid.org/0000-0001-8638-2772
+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.  View all articles by this author
+James Brett Case https://orcid.org/0000-0001-7331-5511
+Department of Medicine, [[:Washington University St. Louis]], MO 63130, USA.
+Roles: Investigation and Validation.  View all articles by this author
+Jeffrey R. Currier https://orcid.org/0000-0002-5696-0268
+[[:Viral Diseases Branch]], [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Investigation, Methodology, Project administration, and Resources.
+View all articles by this author
+Kerri G. Lal
+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: Formal analysis and Investigation.  View all articles by this author
+Sebastian Molnar https://orcid.org/0000-0002-0171-8001
+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, Methodology, Resources, and Validation.
+View all articles by this author
+Manoj S. Nair https://orcid.org/0000-0002-5994-3957
+[[:Diamond AIDS Research Center]], [[:Columbia University]] Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
+Roles: Investigation, Methodology, Resources, and Validation  View all articles by this author
+Vincent Dussupt https://orcid.org/0000-0002-8579-6356
+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, Methodology, and Resources.  View all articles by this author
+Sharon P. Daye
+[[:Center for Infectious Diseases Research]], [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Investigation, and Methodology.  View all articles by this author
+Xiankun Zeng https://orcid.org/0000-0003-3526-8755
+Division of Pathology, [[:United States Army Medical Research Institute of Infectious Diseases]], Frederick, MD 21702, USA.   Role: Investigation   View all articles by this author
+Erica K. Barkei https://orcid.org/0000-0003-1120-7894
+[[:Veterinary Pathology Department]], [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Investigation, Methodology, Resources, Validation, Visualization, and Writing - original draft.  View all articles by this author
+Hilary M. Staples
+Department of Virology and Immunology, [[:Texas Biomedical Research Institute]], San Antonio, TX 78227, USA.  Role: Investigation. View all articles by this author
+Kendra Alfson https://orcid.org/0000-0001-6031-5360
+Department of Virology and Immunology, [[:Texas Biomedical Research Institute]], San Antonio, TX 78227, USA.
+Role: Investigation. View all articles by this author
+Ricardo Carrion https://orcid.org/0000-0001-7046-7683
+Department of Virology and Immunology, [[:Texas Biomedical Research Institute]], San Antonio, TX 78227, USA.
+Roles: Methodology, Project administration, Resources, and Writing - review & editing.
+View all articles by this author
+Shelly J. Krebs https://orcid.org/0000-0003-1136-1760
+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, Data curation, Methodology, Project administration, Resources, and Validation.
+View all articles by this author
+Dominic Paquin-Proulx https://orcid.org/0000-0003-1407-3414
+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.  View all articles by this author
+Nicos Karasavva https://orcid.org/0000-0001-7372-4294
+[[: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, Formal analysis, Investigation, Methodology, Project administration, Validation, and Writing - review & editing.
+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, Project administration, Validation, Visualization, and Writing - review & editing. View all articles by this author
+Linda L. Jagodzinski https://orcid.org/0000-0003-3142-8643
+Diagnostics and Countermeasures Branch, [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, and Writing - review & editing.  View all articles by this author
+Mihret F. Amare https://orcid.org/0000-0002-2696-6116
+[[: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, Funding acquisition, Project administration, and Resources.
+View all articles by this author
+Sandhya Vasan https://orcid.org/0000-0002-6378-6288
+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, Funding acquisition, Methodology, Project administration, Supervision, and Writing - review & editing. View all articles by this author
+Paul T. Scott https://orcid.org/0000-0002-2348-4541
+Emerging Infectious Diseases Branch, [[:Walter Reed Army Institute of Research]] ([[:WRAIR]]), Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, and Writing - review & editing. View all articles by this author
+Yaoxing Huang https://orcid.org/0000-0001-6270-1644
+[[:Diamond AIDS Research Center]], [[:Columbia University]] Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
+Roles: Investigation, Methodology, and Validation. View all articles by this author
+David D. Ho https://orcid.org/0000-0003-1627-149X
+[[:Diamond AIDS Research Center]], [[:Columbia University]] Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
+Roles: Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, and Writing - review & editing.
+View all articles by this author
+Natalia de Val https://orcid.org/0000-0002-1506-2023
+Center for Molecular Microscopy, [[:Center for Cancer Research]], [[:National Cancer Institute]], [[:National Institutes of Health]], Frederick, MD 21702, USA.
+Roles: Conceptualization, Formal analysis, Investigation, Validation, and Writing - review & editing.
+View all articles by this author
+Michael S. Diamond https://orcid.org/0000-0002-8791-3165
+Department of Medicine, [[:Washington University St. Louis]], MO 63130, USA.
+Department of Pathology and Immunology, Washington University, St. Louis, MO 63130, USA.
+Department of Molecular Microbiology, Washington University, St. Louis, MO 63130, USA.
+Roles: Conceptualization, Formal analysis, Funding acquisition, Project administration, Supervision, Validation, and Writing - review & editing. View all articles by this author
+Mark G. Lewis https://orcid.org/0000-0001-7852-0135
+[[:Bioqual]], Rockville, MD 20850, USA.
+Roles: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Supervision, and Validation. View all articles by this author
+Mangala Rao https://orcid.org/0000-0001-9553-4969
+U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, and Validation. View all articles by this author
+Gary R. Matyas https://orcid.org/0000-0002-2074-2373
+U.S. [[:Military HIV Research Program]], [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Investigation, Resources, and Writing - review & editing.
+View all articles by this author
+Gregory D. Gromowski https://orcid.org/0000-0003-4576-4277
+Viral Diseases Branch, [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, and Writing - review & editing. View all articles by this author
+Sheila A. Peel
+[[:Diagnostics and Countermeasures Branch]], [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, and Visualization.
+View all articles by this author
+Nelson L. Michael https://orcid.org/0000-0001-5882-5548
+Center for Infectious Diseases Research, [[:WRAIR]], Silver Spring, MD 20910, USA.
+Roles: Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Supervision, Validation, Writing - original draft, and Writing - review & editing.
+View all articles by this author
+Diane L. Bolton https://orcid.org/0000-0003-1897-499X
+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, Formal analysis, Methodology, Project administration, Supervision, Validation, and Writing - review & editing. View all articles by this author
+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, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, and Writing - review & editing. View all articles by this author
+Funding Information - U.S. [[:Department of Defense]]
+Notes - Corresponding author. Email: kayvon.modjarrad.civ@mail.mil (K.M.); gjoyce@eidresearch.org (M.G.J.)  ((https://web.archive.org/web/20211216192220/https://www.science.org/doi/10.1126/scitranslmed.abi5735))
+==== Link Dump ====
+{{ ::sars-cov-2_genome_match_2015_studies.png?400|}}
 Spike protein clotting
@@ Line 28: / Line 420: @@
+SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2:
+https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318902
+The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice:
+https://pubmed.ncbi.nlm.nih.gov/33328624/
+The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier:
+https://pubmed.ncbi.nlm.nih.gov/33053430/
+The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147-receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease:
+https://www.biorxiv.org/content/10.1101/2020.12.21.423721v2.full.pdf
+Clearing up misinformation about the spike protein and COVID vaccines:
+https://joomi.substack.com/p/coming-soon