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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (547)

ProteinS (185)

ComplexRdRp (33)

ProteinE (33)

ORF1ab (27)


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SARS-CoV-2 Proteins
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    Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Dynamics Tracking

    Authors: Hui Chen; Zhao Li; Sheng Feng; Anni Wang; Melissa Richard-Greenblatt; Emily Hutson; Stefen Andrianus; Laurel Glaser; Kyle G Rodino; Jianing Qian; Dinesh Jayaraman; Ronald Collman; Abigail L Glascock; Frederic Bushman; Jae Seung Lee; Sara Cherry; Alejandra Fausto; Susan R Weiss; Hyun Koo; Patricia M Corby; Una ODoherty; Alfred L Garfall; Dan T Vogl; Edward A Stadtmauer; Ping Wang

    doi:10.1101/2021.03.17.21253847 Date: 2021-03-26 Source: medRxiv

    Background: Little is known about the dynamics of SARS-CoV-2 antigen burden in respiratory samples in different patient populations at different stages of infection. Current rapid antigen tests cannot quantitate and track antigen dynamics with high sensitivity and specificity in respiratory samples. Methods: We developed and validated an ultra-sensitive SARS-CoV-2 antigen assay with smartphone readout using the Microbubbling Digital Assay previously developed by our group, which is a platform that enables highly sensitive detection and quantitation of protein biomarkers. A computer vision-based algorithm was developed for microbubble smartphone image recognition and quantitation. A machine learning-based classifier was developed to classify the smartphone images based on detected microbubbles. Using this assay, we tracked antigen dynamics in serial swab samples from COVID patients hospitalized in ICU and immunocompromised COVID patients. Results: The limit of detection (LOD) of the Microbubbling SARS-CoV-2 Antigen Assay was 0.5 pg/mL (10.6 fM) recombinant nucleocapsid (N PROTEIN) antigen or 4000 copies/mL inactivated SARS-CoV-2 virus in nasopharyngeal (NP) swabs, comparable to many rRT-PCR methods. The assay had high analytical specificity towards SARS-CoV-2. Compared to EUA-approved rRT-PCR methods, the Microbubbling Antigen Assay demonstrated a positive percent agreement (PPA) of 97% (95% confidence interval (CI), 92-99%) in symptomatic individuals within 7 days of symptom onset and positive SARS-CoV-2 nucleic acid results, and a negative percent agreement (NPA) of 97% (95% CI, 94-100%) in symptomatic and asymptomatic individuals with negative nucleic acid results. Antigen positivity rate in NP swabs gradually decreased as days-after-symptom-onset increased, despite persistent nucleic acid positivity of the same samples. The computer vision and machine learning-based automatic microbubble image classifier could accurately identify positives and negatives, based on microbubble counts and sizes. Total microbubble volume, a potential marker of antigen burden, correlated inversely with Ct values and days-after-symptom-onset. Antigen was detected for longer periods of time in immunocompromised patients with hematologic malignancies MESHD, compared to immunocompetent individuals. Simultaneous detectable antigens and nucleic acids may indicate the presence of replicating viruses in patients with persistent infections. Conclusions: The Microbubbling SARS-CoV-2 Antigen Assay enables sensitive and specific detection of acute infections MESHD, and quantitation and tracking of antigen dynamics in different patient populations at various stages of infection. With smartphone compatibility and automated image processing, the assay is well-positioned to be adapted for point-of-care diagnosis and to explore the clinical implications of antigen dynamics in future studies.

    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.

    Detection of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in a fourplex real-time quantitative reverse transcription-PCR assays.

    Authors: Mathieu Durand; Philippe Thibault; Simon Levesque; Ariane Brault; Alex Carignan; Louis Valiquette; Philippe Martin; Simon Labbe

    doi:10.1101/2021.03.23.21254196 Date: 2021-03-26 Source: medRxiv

    The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections MESHD is required to identify and isolate contagious patients to prevent further transmission of the coronavirus disease 2019 MESHD ( COVID-19 MESHD). In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give SARS-CoV-2 a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N PROTEIN) genes. Furthermore, a newly developed primer-probe set targeted human beta-2 microglobulin HGNC ( B2M HGNC) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected less than or equal to 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of 9 logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to detect multiple viral target sequences containing typical mutations of SARS-CoV-2 variants in a single reaction, allowing quicker detection of circulating relevant variants.

    Emergence of N antigen SARS-CoV-2 genetic variants escaping detection of antigenic tests

    Authors: Claudia Del Vecchio; Giuseppina Brancaccio; Alessandra Rosalba Brazzale; Enrico Lavezzo; Francesco Onelia; Elisa Franchin; Laura Manuto; Federico Bianca; Vito Cianci; Annamaria Cattelan; Stefano Toppo; Andrea Crisanti

    doi:10.1101/2021.03.25.21253802 Date: 2021-03-26 Source: medRxiv

    SARS-CoV-2 genetic variants are emerging as a major threat to vaccination efforts worldwide as they may increase virus transmission rate and/or confer the ability to escape vaccine induced immunity with knock on effects on the level of herd immunity and vaccine efficacy respectively. These variants concern the Spike protein PROTEIN, which is encoded by the S gene, involved in virus entry into host cells and the major target of vaccine development. We report here that genetic variants of the N gene PROTEIN can impair our ability to utilize antigenic tests for both diagnosis and mass testing efforts aimed at controlling virus transmission. While conducting a large validation study on the Abbott Panbio COVID-19 MESHD Ag test, we noticed that some swab samples failed to generate a positive result in spite of a high viral load in Rt-PCR assays. Sequencing analysis of viruses showing discordant results in the Rt-PCR and antigen assays revealed the presence of multiple disruptive amino-acid substitutions in the N antigen (the viral protein detected in the antigen test) clustered from position 229 to 374 a region known to contain an immunodominant epitope. A relevant fraction of the variants, undetected by the antigen test, contained the mutations A376T coupled to M241I. Intriguingly we found that virus sequences with this mutation were over-represented in the antigen-test-negative and PCR-positive samples and progressively increased in frequency over time in Veneto, a region of Italy that has aggressively scaled up the utilization of antigen tests, which reached nearly 68% of all the SARS-CoV-2 swab assays performed there. We speculate that mass utilization of antigen assays could create a selection pressure on the target that may favor the spread of undetectable virus variants.

    Arginine Methylation Regulates SARS-CoV-2 Nucleocapsid Protein PROTEIN Function and Viral Replication

    Authors: Ting Cai; Zhenbao Yu; Zhen Wang; Chen Liang; Stephane Richard

    doi:10.1101/2021.03.24.436822 Date: 2021-03-24 Source: bioRxiv

    Viral proteins are known to be methylated by host protein arginine methyltransferases (PRMTs) playing critical roles during viral infections. Herein, we show that PRMT1 HGNC methylates SARS-CoV-2 nucleocapsid (N) protein PROTEIN at residues R95 and R177 within RGG/RG sequences. Arginine methylation of N protein PROTEIN was confirmed by immunoblotting viral proteins extracted from SARS-CoV-2 virions isolated by cell culture. We demonstrate that arginine methylation of N protein PROTEIN is required for its RNA binding capacity, since treatment with a type I PRMT inhibitor (MS023) or substitution of R95K or R177K inhibited interaction with the 5'-UTR of the SARS-CoV-2 genomic RNA. We defined the N interactome in HEK293 cells with or without MS023 treatment and identified PRMT1 HGNC and many of its RGG/RG substrates including the known interactor, G3BP1 HGNC, and other components of stress granules (SG). Methylation of N protein PROTEIN at R95 regulates another function namely its property to suppress the formation of SGs. MS023 treatment or R95K substitution blocked N-mediated suppression of SGs. Also, the co-expression of methylarginine reader TDRD3 HGNC quenched N-mediated suppression of SGs in a dose-dependent manner. Finally, pre-treatment of VeroE6 cells with MS023 significantly reduced SARS-CoV-2 replication. With type I PRMT inhibitors being in clinical trials for cancer MESHD treatment, inhibiting arginine methylation to target the later stages of the viral life cycle such as viral genome packaging and assembly of virions may be an additional therapeutic application of these drugs.

    Weak humoral immune reactivity among residents of long-term care facilities following one dose of the BNT162b2 mRNA COVID-19 MESHD vaccine

    Authors: Mark A Brockman; Francis Mwimanzi; Yurous Sang; Kurtis Ng; Olga Agafitei; Siobhan Ennis; Hope Lapointe; Landon Young; Gisele Umviligihozo; Laura Burns; Chanson J Brumme; Victor Leung; Julio S G Montaner; Daniel Holmes; Mari DeMarco; Janet Simons; Masahiro Niikura; Ralph Pantophlet; Marc G Romney; Zabrina L Brumme

    doi:10.1101/2021.03.17.21253773 Date: 2021-03-24 Source: medRxiv

    Background. Several Canadian provinces are extending the interval between COVID-19 MESHD vaccine doses to increase population vaccine coverage more rapidly. However, immunogenicity of these vaccines after one dose is incompletely characterized, particularly among the elderly, who are at greatest risk of severe COVID-19 MESHD. Methods. We assessed SARS-CoV-2 humoral responses pre-vaccine and one month following the first dose of BNT162b2 mRNA vaccine, in 12 COVID-19 MESHD seronegative residents of long-term care facilities (median age, 82 years), 18 seronegative healthcare workers (HCW; median age, 36 years) and 4 convalescent HCW. Total antibody responses to SARS-CoV-2 nucleocapsid (N PROTEIN) and spike protein PROTEIN receptor binding domain (S/RBD) were assessed using commercial immunoassays. We quantified IgG and IgM responses to S/RBD and determined the ability of antibodies to block S/RBD binding to ACE2 HGNC receptor using ELISA. Neutralizing antibody activity was also assessed using pseudovirus and live SARS-CoV-2. Results. After one vaccine dose, binding antibodies against S/RBD were ~4-fold lower in residents compared to HCW (p<0.001). Inhibition of ACE2 HGNC binding was 3-fold lower in residents compared to HCW (p=0.01) and pseudovirus neutralizing activity was 2-fold lower (p=0.003). While six (33%) seronegative HCW neutralized live SARS-CoV-2, only one (8%) resident did (p=0.19). In contrast, convalescent HCW displayed 7- to 20-fold higher levels of binding antibodies and substantial ability to neutralize live virus after one dose. Interpretation. Extending the interval between COVID-19 MESHD vaccine doses may pose a risk to the elderly due to lower vaccine immunogenicity in this group. We recommend that second doses not be delayed in elderly individuals.

    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.

    New detection of SARS-CoV-2 in two cats height months after COVID-19 MESHD outbreak appearance in France

    Authors: Matthieu Fritz; Nicolas Nesi; Solene Denolly; Bertrand Boson; Vincent Legros; Serge G. Rosolen; Alexandra Briend-Marchal; Meriadeg Ar Gouil; Eric M. Leroy

    doi:10.1101/2021.03.24.436830 Date: 2021-03-24 Source: bioRxiv

    Although there are several reports in the literature of SARS-CoV-2 infection MESHD in cats, few SARS-CoV-2 sequences from infected cats have been published. In this report, SARS-CoV-2 infection MESHD was evaluated in two cats by clinical observation, molecular biology (qPCR and NGS), and serology (Microsphere immunoassay and seroneutralization). Following the observation of symptomatic SARS-CoV-2-infection MESHD in two cats, infection status was confirmed by RT-qPCR and, in one cat, serological analysis for antibodies against N-protein PROTEIN and S-protein PROTEIN, as well as neutralizing antibodies. Comparative analysis of five SARS-CoV-2 sequence-fragments obtained from one of the cats showed that this infection was not with one of the three recently emerged variants of SARS-CoV-2. This study provides additional information on the clinical, molecular, and serological aspects of SARS-CoV-2 infection MESHD in cats.

    The Dual-Antigen Ad5 COVID-19 MESHD Vaccine Delivered as an Intranasal Plus Subcutaneous Prime Elicits Th1 Dominant T-Cell and Humoral Responses in CD-1 Mice

    Authors: Adrian Rice; Mohit Verma; Annie Shin; Lise Zakin; Peter Sieling; Shiho Tanaka; Joseph Balint; Kyle Dinkins; Helty Adisetiyo; Brett Morimoto; Justin Taft; Roosheel Sandeep Patel; Sofija Buta; Marta Martin-Fernandez; Dusan Bogunovic; Patricia R Spilman; Elizabeth R Gabitzsch; Jeffrey T Safrit; Shahrooz Rabizadeh; Kayvan Niazi; Patrick Soon-Shiong

    doi:10.1101/2021.03.22.436476 Date: 2021-03-23 Source: bioRxiv

    In response to the need for an efficacious, thermally-stable COVID-19 MESHD vaccine that can elicit both humoral and cell-mediated T-cell responses, we have developed a dual-antigen human adenovirus serotype 5 (hAd5) COVID-19 MESHD vaccine in formulations suitable for subcutaneous (SC), intranasal (IN), or oral delivery. The vaccine expresses both the SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S) and nucleocapsid (N) proteins PROTEIN using an hAd5 platform with E1, E2b, and E3 sequences deleted; hAd5(E1-, E2b-, E3-); that is effective even in the presence of hAd5 immunity. In the vaccine, S is modified (S-Fusion) for enhanced cell surface display to elicit humoral responses and N is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal pathway to increase MHC I and II presentation. Initial studies using subcutaneous (SC) prime and SC boost vaccination of CD-1 mice demonstrated that the hAd5 S-Fusion + N-ETSD vaccine elicits T-helper cell 1 (Th1) dominant T-cell and humoral responses to both S and N. We then compared SC to IN prime vaccination with either an SC or IN boost post-SC prime and an IN boost after IN prime. These studies reveal that IN prime/IN boost is as effective at generating Th1 dominant humoral responses to both S and N as the other combinations, but that the SC prime with either an IN or SC boost elicits greater T cell responses. In a third study to assess the power of the two routes of delivery when used together, we used a combined SC plus IN prime with or without a boost and found the combined prime alone to be as effective as the combined prime with either an SC or IN boost in generating both humoral and T-cell responses. The findings here in CD-1 mice demonstrate that combined SC and IN prime-only delivery has the potential to provide broad immunity, including mucosal immunity, against SARS-CoV-2 and supports further testing of this delivery approach in additional animal models and clinical trials.

    Clonal dissection of immunodominance and cross-reactivity of the CD4 HGNC+ T cell response to SARS-CoV-2

    Authors: Jun Siong Low; Daniela Vaqueirinho; Federico Mele; Mathilde Foglierini; Michela Perotti; David Jarrossay; Sandra Jovic; Tatiana Terrot; Alessandra Franzetti Pellanda; Maira Biggiogero; Christian Garzoni; Paolo Ferrari; Alessandro Ceschi; Antonio Lanzavecchia; Antonino Cassotta; Federica Sallusto

    doi:10.1101/2021.03.23.436642 Date: 2021-03-23 Source: bioRxiv

    The identification of CD4 HGNC+ T cell epitopes is essential for the design of effective vaccines capable of inducing neutralizing antibodies and long-term immunity. Here we demonstrate in COVID-19 MESHD patients a robust CD4 HGNC+ T cell response to naturally processed SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD and Nucleoprotein PROTEIN, including effector, helper and memory T cells. By characterizing 2,943 Spike-reactive T cell clones, we found that 34% of the clones and 93% of the patients recognized a conserved immunodominant region encompassing residues S346-365 in the RBD and comprising three nested HLA-DR and HLA-DP HGNC restricted epitopes. By using pre- and post- COVID-19 MESHD samples and Spike proteins PROTEIN from alpha and beta coronaviruses, we provide in vivo evidence of cross-reactive T cell responses targeting multiple sites in the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein. The possibility of leveraging immunodominant and cross-reactive T helper epitopes is instrumental for vaccination strategies that can be rapidly adapted to counteract emerging SARS-CoV-2 variants.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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