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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (66)

ProteinN (9)

NSP5 (5)

ORF8 (1)

NSP3 (1)


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SARS-CoV-2 Proteins
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    Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants

    Authors: Christy L. Lavine; Shaun Rawson; Haisun Zhu; Krishna Anand; Pei Tong; Avneesh Gautam; Shen Lu; Sarah Sterling; Richard M Walsh Jr.; Jianming Lu; Wei Yang; Michael S Seaman

    doi:10.1101/2021.04.13.439709 Date: 2021-04-14 Source: bioRxiv

    Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) have become the dominant circulating strains that continue to fuel the COVID-19 pandemic MESHD despite intensive vaccination efforts throughout the world. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Mutations in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). The enhanced receptor engagement can account for the increased transmissibility and risk of mortality as the variant may begin to infect efficiently infect MESHD additional cell types expressing low levels of ACE2 HGNC. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein PROTEIN, rendering complete resistance to some potent neutralizing antibodies. These findings provide structural details on how the wide spread of SARS-CoV-2 enables rapid evolution to enhance viral fitness MESHD and immune evasion. They may guide intervention strategies to control the pandemic.

    Bead-assisted SARS-CoV-2 multi-antigen serological test allows effective identification of patients

    Authors: Yaiza Caceres-Martell; Daniel Fernandez-Soto; Carmen Campos-Silva; Eva Maria Garcia-Cuesta; Jose M. Casasnovas; David Navas-Herrera; Alexandra Beneitez-Martinez; Pedro Martinez-Fleta; Arantzazu Alfranca; Francisco Sanchez-Madrid; Gabriela Escudero-Lopez; Carlos Vilches; Ricardo Jara-Acevedo; Hugh T. Reyburn; Jose M. Rodriguez-Frade; Mar Vales-Gomez

    doi:10.1101/2021.04.08.21254348 Date: 2021-04-10 Source: medRxiv

    Many new aspects of COVID-19 MESHD disease, including different clinical manifestations, have been identified during the pandemic. The wide array of symptoms and variation in disease severity after SARS-CoV-2 infection MESHD might be related to heterogeneity in the immune responses of different patients. Here we describe a new method for a simple multi-antigen serological test that generates a full picture of seroconversion in a single reaction. The assay is based on the detection by flow cytometry of multiple immunoglobulin classes (isotypes) specific for four SARS-CoV-2 antigens: the Spike glycoprotein PROTEIN (one of the highly immunogenic proteins), its RBD fragment (the major target for neutralising antibodies), the nucleocapsid protein PROTEIN and the main cysteine-like protease PROTEIN. Until now, most diagnostic serological tests measured antibodies to only one antigen and some patients seemed to not make any antibody response. Our data reveal that while most patients respond against all the viral antigens tested, others show a marked bias to make antibodies against either proteins exposed on the viral particle or those released after cellular infection. Combining all the four antigens and using machine learning techniques, it was possible to clearly discriminate between patients and healthy controls with 100% confidence. Further, combination of antigens and different immunoglobulin isotypes in this multi-antigen assay improved the classification of patients with mild and severe disease. Introduction of this method will facilitate massive screenings of patients to evaluate their immune response. It could also support vaccination campaigns both to select non-immune individuals and to distinguish infected MESHD patients from vaccine responders.

    mRNA vaccination compared to infection elicits an IgG-predominant response with greater SARS-CoV-2 specificity and similar decrease in variant spike recognition

    Authors: Katharina Roeltgen; Sandra C.A. Nielsen; Prabhu S Arunachalam; Fan Yang; Ramona A. Hoh; Oliver F. Wirz; Alexandra S Lee; Fei Gao; Vamsee Mallajosyula; Chunfeng Li; Emily Haraguchi; Massa J Shoura; James L Wilbur; Jacob N. Wohlstadter; Mark M. Davis; Benjamin A. Pinsky; George B. Sigal; Bali Pulendran; Kari C. Nadeau; Scott D. Boyd

    doi:10.1101/2021.04.05.21254952 Date: 2021-04-07 Source: medRxiv

    During the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike PROTEIN protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected MESHD patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 MESHD patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected MESHD patients exposed to Wuhan-Hu-1 antigens.

    Single Prime hAd5 Spike (S) + Nucleocapsid (N PROTEIN) Dual Antigen Vaccination of Healthy Volunteers Induces a Ten-Fold Increase in Mean S- and N- T-Cell Responses Equivalent to T-Cell Responses from Patients Previously Infected with SARS-CoV-2

    Authors: Pete Sieling; Thomas King; Raymond Wong; Andy Nguyen; Kamil Wnuk; Elizabeth R Gabitzsch; Adrian Rice; Helty Adisetiyo; Melanie Hermreck; Mohit Verma; Lise Zakin; Annie Shin; Brett Morimoto; Wendy Higashide; Kyle Dinkins; Joseph Balint; Victor Peykov; Justin Taft; Roosheel Patel; Sofija Buta; Marta Martin-Fernandez; Dusan Bogunovic; Patricia Spilman; Lennie Sender; Sandeep Reddy; Philip Robinson; Shahrooz Rabizadeh; Kayvan Niazi; Patrick Soon-Shiong

    doi:10.1101/2021.04.05.21254940 Date: 2021-04-07 Source: medRxiv

    In response to the need for a safe, efficacious vaccine that provides broad immune protection against SARS-CoV-2 infection MESHD, we have developed a dual-antigen COVID-19 MESHD vaccine. The vaccine delivers both the viral spike (S) protein PROTEIN modified to increase cell-surface expression (S-Fusion) and the viral nucleocapsid (N) protein PROTEIN with an Enhanced T-cell Stimulation Domain (N-ETSD) to enhance MHC class I and II presentation and T-cell responses. The vaccine antigens are delivered using a human adenovirus serotype 5 (hAd5) platform with E1, E2b, and E3 regions deleted that has been shown in previous cancer MESHD vaccine studies to be effective in the presence of pre-existing hAd5 immunity. Here, we demonstrate the hAd5 S-Fusion + N-ETSD (hAd5 S + N) vaccine antigens when expressed by dendritic cells (DCs) of previously SARS-CoV-2-infected MESHD patients elicit Th1 HGNC dominant activation of autologous patient T cells, indicating the vaccine antigens have the potential for generating immune responses in patients previously infected MESHD or vaccinated. We further demonstrate that participants in our open-label Phase 1b study of the dual-antigen hAd5 S + N vaccine generate Th1 HGNC dominant S- and N- specific T cells after a single prime subcutaneous injection and that the magnitude of these responses were comparable to those seen for T cells from previously infected patients. We further present our in silico prediction of T-cell epitope HLA binding for both the first-wave SARS-CoV-2 A strain and the K417N, E484K, and N501Y S as well as the T201I N variants that suggests T-cell responses to the hAd5 S + N vaccine will retain efficacy against these variants. These findings that the dual-antigen hAd5 S + N vaccine elicits SARS-CoV-2-relevant T-cell responses and that such cell-mediated protection is likely to be sustained against emerging variants supports the testing of this vaccine as a universal booster that would enhance and broaden existing immune protection conferred by currently approved S-based vaccines.

    Detection of cross-reactive IgA in saliva against SARS-CoV-2 Spike1 subunit

    Authors: Keiichi Tsukinoki; Tatsuo Yamamoto; Keisuke Handa; Mariko Iwamiya; Satoshi Ino; Takashi Sakurai

    doi:10.1101/2021.03.29.21253174 Date: 2021-04-01 Source: medRxiv

    Abundant secretory IgA (sIgA) in mucus, breast milk MESHD, and saliva provides immunity that prevents infection of mucosal surfaces. sIgA in pre-pandemic breast milk samples have been reported to cross-react with SARS-CoV-2, but whether it also occurs in saliva and, if so, whether it cross-reacts with SARS-CoV-2, has remained unknown. We aimed to clarify whether sIgA in saliva cross-reacts with SARS-CoV-2 spike PROTEIN 1 subunit in individuals who have not been infected MESHD with this virus. The study included 137 (male, n = 101; female, n = 36; mean age, 38.7 [from 24 to 65] years) of dentists and doctors in the Kanagawa Dental University Hospital. Saliva and blood samples were analyzed by PCR and immunochromatography for IgG and IgM, respectively. We then identified patients with saliva samples that were confirmed as PCR- and IgM-negative for COVID-19 MESHD. Proportions of SARS-CoV-2 cross-reactive IgA-positive individuals were determined by enzyme-linked immunosorbent assay using a biotin-labeled spike S1-mFc recombinant protein covering the receptor-binding domain of SARS-CoV-2. The proportion of SARS-CoV-2 cross-reactive IgA-positive individuals was 46.7%, and this correlated negatively with age (r = -0.218, p = 0.01). The proportion of IgA-positive individuals [≥] 50 y was significantly lower than that of patients aged [≤] 49 y (p = 0.005). sIgA was purified from the saliva of all patients, and the salivary sIgA was found to suppress the binding of SARS-CoV-2 spike PROTEIN protein to the ACE-2 receptor. We found SARS-CoV-2 cross-reactive sIgA in the saliva of some participants who had never been infected with the virus, suggesting that sIgA helps prevent SARS-CoV-2 infection MESHD

    Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines

    Authors: Nick A Kennedy; Simeng Lin; James R Goodhand; Neil Chanchlani; - CLARITY IBD Contributors; Nick Powell; Tariq Ahmad

    doi:10.1101/2021.03.25.21254335 Date: 2021-03-28 Source: medRxiv

    Background Delayed second-dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease MESHD treated with infliximab have attenuated serological responses to a single-dose of a SARS-CoV-2 vaccine. Methods Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared to a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin a4B7 monoclonal antibody. Our primary outcome was anti- SARS-CoV-2 spike PROTEIN (S) antibody concentrations 3-10 weeks after vaccination in patients without evidence of prior infection MESHD. Secondary outcomes were seroconversion rates, and antibody responses following past infection or a second dose of the BNT162b2 vaccine. Findings Geometric mean [SD] anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL [5.9] vs 28.8 U/mL [5.4] P<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL [4.9]) vs 13.8 U/mL [5.9] P<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab- compared to vedolizumab-treated patients who received the BNT162b2 (fold change [FC] 0.29 [95% CI 0.21, 0.40], p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 [95% CI 0.30, 0.51], p<0.0001) vaccines. In both models, age > 59 years, immunomodulator use, Crohn's disease MESHD, and smoking were associated with lower, whilst non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single-dose of either vaccine were higher in patients with prior SARS-CoV-2 infection MESHD and after two doses of BNT162b2 vaccine. Interpretation Infliximab is associated with attenuated immunogenicity to a single-dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection MESHD, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. Funding Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts. Unrestricted educational grants: F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea) and Galapagos NV (Belgium).

    Multiplex Antibody Analysis of IgM, IgA HGNC and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts

    Authors: Carlota Dobano; Selena Alonso; Marta Vidal; Alfons Jimenez; Rocio Rubio; Rebeca Santano; Diana Barrios; Gemma Pons Tomas; Maria Mele Casas; Maria Hernandez Garcia; Monica Girona-Alarcon; Laura Puyol; Natalia Rodrigo Melero; Carlo Carolis; Aleix Garcia-Miquel; Elisenda Bonet-Carne; Joana Claverol; Marta Cubells; Claudia Fortuny; Victoria Fumado; Anna Codina; Quique Bassat; Carmen Munoz-Almagro; Mariona Fernandez de Sevilla; Eduard Gratacos; Luis Izquierdo; Juan Jose Garcia-Garcia; Ruth Aguilar; Iolanda Jordan; Gemma Moncunill

    doi:10.1101/2021.03.22.21254120 Date: 2021-03-26 Source: medRxiv

    COVID-19 MESHD affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions. We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA HGNC and IgG antibodies against five SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S) and nucleocapsid (N PROTEIN) antigens in the context of a contacts and infectivity longitudinal MESHD study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain. Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection MESHD were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected MESHD individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary. In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection MESHD. Saliva antibody detection could allow determining COVID-19 MESHD prevalence in pediatric populations, alternative to bleeding MESHD or nasal swab, and serological diagnosis following vaccination.

    First Description of Natural SARS-CoV-2 Infection MESHD in Two Wild American Minks ( Neovison vison) MESHD

    Authors: Jordi Aguiló-Gisbert; Miguel Padilla-Blanco; Victor Lizana; Elisa Maiques; Marta Muñoz Baquero; Eva Chillida-Martínez; Jesús Cardells; Consuelo Rubio-Guerri

    id:10.20944/preprints202103.0647.v1 Date: 2021-03-25 Source: Preprints.org

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19 MESHD , is considered a pathogen with animal origin, mainly transmitted human to human. It has been experimentally and naturally demonstrated that several animals can be infected by SARS-CoV-2. There are strong evidences that minks are highly susceptible to SARS-CoV-2 infection MESHD, since several cases of human to mink infection have been reported, and it has been suggested mink to human infection exists, which so far it is the most reliable example of a zoonotic event of COVID-19 MESHD . However, all these cases reported are form mink farms, with the exception of one case in the USA in which the virus was detected in a mink located in the wild, but it was demonstrated that the animal was infected on a fur farm. In the present work, we have detected SARS-CoV-2 RNA in two wild American minks (Neovison vison) in Valencian Community (Eastern Spain) during invasive species trapping campaigns. The animals were trapped from areas known for harbouring self-sustained populations, far away from the nearest fur farm. SARS-CoV-2 RNA was detected in mesenteric lymph nodes samples by RT-PCR. A partial region of the Spike protein PROTEIN gene was amplified and sequence obtaining a 397 nt size sequence. Phylogenetic analysis shown that both sequences were identical to the consensus variant SARS CoV-2 sequence (from Wuhan). This research describes the first infection report of a true wild American mink not related to infected fur farms MESHD or direct contact with humans, which is believed to be the first example of wild animals in which SARS-CoV-2 has been detected.

    3D visualization of SARS-CoV-2 infection MESHD and receptor distribution in Syrian hamster lung lobes display distinct spatial arrangements

    Authors: Ilhan Tomris; Kim M Bouwman; Youri Adolfs; Danny Noack; Roosmarijn van der Woude; Sander Herfst; Geert-Jan Boons; Bart Haagmans; R. Jeroen Pasterkamp; Barry Rockx; Robert Paul de Vries

    doi:10.1101/2021.03.24.435771 Date: 2021-03-24 Source: bioRxiv

    SARS-CoV-2 attaches to angiotensin-converting enzyme 2 (ACE2) to gain entry into cells after which the spike protein PROTEIN is cleaved by the transmembrane serine protease 2 (TMPRRS2) to facilitate viral-host membrane fusion. ACE2 and TMPRRS2 expression profiles have been analyzed at the genomic, transcriptomic, and single-cell RNAseq level, however, biologically relevant protein receptor organization in whole tissues is still poorly understood. To describe the organ-level architecture of receptor expression, related to the ability of ACE2 and TMPRRS2 to mediate infectivity, we performed a volumetric analysis of whole Syrian hamster lung lobes. Lung tissue of infected MESHD and control animals were stained using antibodies against ACE2 and TMPRRS2, combined with fluorescent spike protein PROTEIN and SARS-CoV-2 nucleoprotein PROTEIN staining. This was followed by light-sheet microscopy imaging to visualize expression patterns. The data demonstrates that infection is restricted to sites with both ACE2 and TMPRRS2, the latter is expressed in the primary and secondary bronchi whereas ACE2 is predominantly observed in the terminal bronchioles and alveoli. Conversely, infection completely overlaps at these sites where ACE2 and TMPRSS2 co-localize.

    Design and proof-of-concept for targeted phage-based COVID-19 MESHD vaccination strategies with a streamlined cold-free supply chain

    Authors: Daniela I. Staquicini; Fenny H. F. Tang; Christopher Markosian; Virginia J. Yao; Fernanda I. Staquicini; Esteban Dodero Rojas; Vinicius G. Contessoto; Deodate Davis; Nazia Habib; Tracey L. Smith; Natalie Bruiners; Richard L. Sidman; Maria L. Gennaro; Steven K. Libutti; Paul C. Whitford; Stephen K. Burley; José Nelson Onuchic; Wadih Arap; Renata Pasqualini

    doi:10.1101/2021.03.15.435496 Date: 2021-03-16 Source: bioRxiv

    Development of effective vaccines against Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) is a global imperative. Rapid immunization of the world human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and many different vaccine approaches are being pursued to meet this task. Engineered filamentous bacteriophage MESHD (phage) have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the design, development, and initial evaluation of targeted phage-based vaccination approaches against Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) by using dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. Towards a unique phage- and AAVP-based dual-display candidate approach, we first performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN for display on the recombinant major capsid coat protein pVIII. Targeted phage particles carrying one of these epitopes induced a strong and specific humoral response. In an initial experimental approach, when these targeted phage particles were further genetically engineered to simultaneously display a ligand peptide (CAKSMGDIVC) on the minor capsid protein pIII, which enables receptor-mediated transport of phage particles from the lung epithelium into the systemic circulation (termed "dual-display"), they enhanced a systemic and specific spike (S) protein PROTEIN-specific antibody response upon aerosolization into the lungs of mice. In a second line of investigation, we engineered targeted AAVP particles to deliver the entire S protein PROTEIN gene under the control of a constitutive cytomegalovirus (CMV) promoter, which induced tissue-specific transgene expression stimulating a systemic S protein PROTEIN-specific antibody response. As proof-of-concept preclinical experiments, we show that targeted phage- and AAVP-based particles serve as robust yet versatile enabling platforms for ligand-directed immunization and promptly yield COVID-19 MESHD vaccine prototypes for further translational development. SignificanceThe ongoing COVID-19 MESHD global pandemic has accounted for over 2.5 million deaths and an unprecedented impact on the health of mankind worldwide. Over the past several months, while a few COVID-19 MESHD vaccines have received Emergency Use Authorization and are currently being administered to the entire human population, the demand for prompt global immunization has created enormous logistical challenges--including but not limited to supply, access, and distribution--that justify and reinforce the research for additional strategic alternatives. Phage are viruses that only infect bacteria MESHD and have been safely administered to humans as antibiotics for decades. As experimental proof-of-concept, we demonstrated that aerosol pulmonary vaccination with lung-targeted phage particles that display short epitopes of the S protein PROTEIN on the capsid as well as preclinical vaccination with targeted AAVP particles carrying the S protein PROTEIN gene elicit a systemic and specific immune response against SARS-CoV-2 in immunocompetent mice. Given that targeted phage- and AAVP-based viral particles are sturdy yet simple to genetically engineer, cost-effective for rapid large-scale production in clinical grade, and relatively stable at room temperature, such unique attributes might perhaps become additional tools towards COVID-19 MESHD vaccine design and development for immediate and future unmet needs.

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