Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (654)

ProteinN (149)

NSP5 (75)

ComplexRdRp (46)

ProteinE (43)


SARS-CoV-2 Proteins
    displaying 21 - 30 records in total 2729
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    Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination

    Authors: Lucie Loyal; Julian Braun; Larissa Henze; Beate Kruse; Manuela Dingeldey; Ulf Reimer; Florian Kern; Tatjana Schwarz; Maike Mangold; Clara Unger; Friederike Doerfler; Shirin Kadler; Jennifer Rosowski; Kuebrah Guercan; Zehra Uyar-Aydin; Marco Frentsch; Florian Kurth; Karsten Schnatbaum; Maren Eckey; Stefan Hippenstiel; Andreas Hocke; Marcel A. Mueller; Birgit Sawitzki; Stefan Miltenyi; Friedemann Paul; Marcus A. Mall; Holger Wenschuh; Sebastian Voigt; Christian Drosten; Roland Lauster; Nils Lachmann; Leif-Erik Sander; Victor Max Corman; Jobst Roehmel; Lil Antonia Meyer-Arndt; Andreas M Thiel; Claudia Giesecke-Thiel

    doi:10.1101/2021.04.01.21252379 Date: 2021-04-05 Source: medRxiv

    While evidence for pre-existing SARS-CoV-2-cross-reactive CD4+ T cells in unexposed individuals is increasing, their functional significance remains unclear. Here, we comprehensively determined SARS-CoV-2-cross-reactivity and human coronavirus-reactivity in unexposed individuals. SARS-CoV-2-cross-reactive CD4+ T cells were ubiquitous, but their presence decreased with age. Within the spike glycoprotein PROTEIN fusion domain, we identified a universal immunodominant coronavirus-specific peptide epitope (iCope). Pre-existing spike- and iCope-reactive memory T cells were efficiently recruited into mild SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD and their abundance correlated with higher IgG titers. Importantly, the cells were also reactivated after primary BNT162b2 COVID-19 MESHD mRNA vaccination in which their kinetics resembled that of secondary immune responses. Our results highlight the functional importance of pre-existing spike-cross-reactive T cells in SARS-CoV-2 infection MESHD and vaccination. Abundant spike-specific cross-immunity may be responsible for the unexpectedly high efficacy of current vaccines even with single doses and the high rate of asymptomatic/mild infection courses.

    Substitutions and codon usage in SARS-CoV-2 in mammals indicate natural selection and host adaptation

    Authors: Zhixiong Lei Sr.; Dan Zhang Sr.; Long Liu

    doi:10.1101/2021.04.04.438417 Date: 2021-04-05 Source: bioRxiv

    The outbreak of COVID-19 MESHD, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD, rapidly spread to create a global pandemic and has continued to spread across hosts from humans to animals, transmitting particularly effectively in mink. How SARS-CoV-2 evolves in animals and humans and the differences in the separate evolutionary processes remain unclear. We analyzed the composition and codon usage bias of SARS-CoV-2 MESHD in infected humans and animals. Compared with other animals, SARS-CoV-2 in mink had the most substitutions. The substitutions of cytidine in SARS-CoV-2 in mink account for nearly 50% of the substitutions, while those in other animals represent only 30% of the substitutions. The incidence of adenine transversion in SARS-CoV-2 in other animals is threefold higher than that in mink-CoV (the SARS-CoV-2 virus in mink). A synonymous codon usage analysis showed that SARS-CoV-2 is optimized to adapt in the animals in which it is currently reported, and all of the animals showed decreased adaptability relative to that of humans, except for mink. A binding affinity analysis indicated that the spike protein PROTEIN of the SARS-CoV-2 variant in mink showed a greater preference for binding with the mink receptor ACE2 than with the human receptor, especially as the mutation Y453F and F486L in mink-CoV lead to improvement of binding affinity for mink receptor. Our study focuses on the divergence of SARS-CoV-2 genome composition and codon usage in humans and animals, indicating possible natural selection and current host adaptation.

    Recovery from acute SARS-CoV-2 infection MESHD and development of anamnestic immune responses in T cell-depleted rhesus macaques

    Authors: Kim J Hasenkrug; Friederike Feldmann; Lara Myers; Mario L Santiago; Kejun Guo; Bradley S Barrett; Kaylee L Mickens; Aaron Carmody; Atsushi Okumura; Deepashri Rao; Madison M Collins; Ronald J Messer; Jamie Lovaglio; Carl Shaia; Rebecca Rosenke; Neeltje van Doremalen; Chad Clancy; Greg Saturday; Patrick Hanley; Brian Smith; Kimberly Meade-White; W. Lesley Shupert; David W. Hawman; Heinz Feldmann

    doi:10.1101/2021.04.02.438262 Date: 2021-04-04 Source: bioRxiv

    Severe COVID-19 MESHD has been associated with T cell lymphopenia MESHD 1,2, but no causal effect of T cell deficiency on disease MESHD severity has been established. To investigate the specific role of T cells in recovery from SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs we studied rhesus macaques that were depleted of either CD4+, CD8+ or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to controls. The T cell-depleted groups developed virus-neutralizing antibody responses and also class-switched to IgG. When re-infected six weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections MESHD, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19 MESHD. Neither primed CD4+ or CD8+ T cells appeared critical for immunoglobulin class switching, the development of immunological memory MESHD or protection from a second infection.

    Estimates and determinants of SARS-CoV-2 seroprevalence and infection fatality MESHD ratio using latent class analysis: the population-based Tirschenreuth study in the hardest-hit German county in spring 2020

    Authors: Ralf Wagner; David Peterhoff; Stephanie Beileke; Felix Guenther; Melanie Berr; Sebastian Einhauser; Anja Schuetz; Hans-Helmut Niller; Philipp Steininger; Antje Knoell; Matthias Tenbusch; Clara Maier; Klaus Korn; Klaus Stark; Andre Gessner; Ralph Burkhardt; Michael Kabesch; Holger Schedl; Helmut Kuechenhoff; Annette B. Pfahlberg; Iris Heid; Olaf Gefeller; Klaus Ueberla

    doi:10.1101/2021.03.29.21254343 Date: 2021-04-04 Source: medRxiv

    SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHD fatality ratios (IFR) remain controversially discussed with implications for political measures, but the number of registered infections depends on testing strategies and deduced case fatality ratios (CFR) are poor proxies for IFR. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020 with particularly high CFR. To estimate seroprevalence, dark figure, and IFR for the Tirschenreuth population aged [≥]14 years in June/July 2020 with misclassification error control, we conducted a population-based study, including home visits for elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests (64% of our random sample). Latent class analysis yielded 8.6% standardized county-wide seroprevalence, dark figure factor 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the dark figure was 12.2 in the young versus 1.7 for [≥]85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60-69, 13.2% for age 70+, confirming a previously reported age-model for IFR. Senior care homes accounted for 45% of COVID-19 MESHD-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient MESHD targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.

    Membrane lectins enhance SARS-CoV-2 infection MESHD and influence the neutralizing activity of different classes of antibodies

    Authors: Florian A. Lempp; Leah Soriaga; Martin Montiel-Ruiz; Fabio Benigni; Julia Noack; Young-Jun Park; Siro Bianchi; Alexandra C. Walls; John E. Bowen; Jiayi Zhou; Hanna Kaiser; Maria Agostini; Marcel Meury; Exequiel Dellota Jr.; Stefano Jaconi; Elisabetta Cameroni; Herbert W. Virgin; Antonio Lanzavecchia; David Veesler; Lisa Purcell; Amalio Telenti; Davide Corti

    doi:10.1101/2021.04.03.438258 Date: 2021-04-04 Source: bioRxiv

    Investigating the mechanisms of SARS-CoV-2 cellular infection MESHD is key to better understand COVID-19 MESHD immunity and pathogenesis. Infection, which involves both cell attachment and membrane fusion, relies on the ACE2 HGNC receptor that is paradoxically found at low levels in the respiratory tract, suggesting that additional mechanisms facilitating infection may exist. Here we show that C-type lectin receptors, DC-SIGN, L-SIGN HGNC and the sialic acid-binding Ig-like lectin 1 HGNC ( SIGLEC1 HGNC) function as auxiliary receptors by enhancing ACE2 HGNC-mediated infection and modulating the neutralizing activity of different classes of spike-specific antibodies. Antibodies to the N-terminal domain ( NTD HGNC) or to the conserved proteoglycan site at the base of the Receptor Binding Domain (RBD), while poorly neutralizing infection of ACE2 HGNC over-expressing cells, effectively block lectin-facilitated infection. Conversely, antibodies to the Receptor Binding Motif ( RBM HGNC), while potently neutralizing infection of ACE2 HGNC over-expressing cells, poorly neutralize infection of cells expressing DC-SIGN or L-SIGN HGNC and trigger fusogenic rearrangement of the spike promoting cell-to-cell fusion. Collectively, these findings identify a lectin-dependent pathway that enhances ACE2 HGNC-dependent infection by SARS-CoV-2 and reveal distinct mechanisms of neutralization by different classes of spike-specific antibodies.

    Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 MESHD golden Syrian hamster model

    Authors: Santosh Dhakal; Camilo A. Ruiz-Bedoya; Ruifeng Zhou; Patrick Creisher; Jason Villano; Kirsten Littlefield; Jennie Castillo; Paula Marinho; Anne Jedlicka; Alvaro Ordonez; Natalia Majewska; Michael Betenbaugh; Kelly Flavahan; Alice Mueller; Monika Looney; Darla Quijada; Filipa Mota; Sarah E. Beck; Jacqueline K Brockhurst; Alicia Braxton; Natalie Castell; Kelly A. Metcalf Pate; Petros C. Karakousis; Joseph L. Mankowski; Andrew Pekosz; Sanjay K Jain; Sabra L. Klein

    doi:10.1101/2021.04.02.438292 Date: 2021-04-04 Source: bioRxiv

    In the ongoing coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) MESHD, more severe outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8-10 weeks of age) were inoculated intranasally with 105 TCID50 of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developing more extensive pneumonia MESHD as noted on chest computed tomography, and recovering more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage MESHD. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including IFNb and TNFa, were comparable between the sexes. However, during the recovery phase of infection, females mounted two-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S PROTEIN-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole inactivated SARS-CoV-2 and mutant S-RBDs MESHD, as well as virus neutralizing antibodies in plasma. The development of an animal model to study COVID-19 MESHD sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2 associated sex differences seen in the human population.

    Genomic monitoring unveil the early detection of the SARS-CoV-2 B.1.351 lineage (20H/501Y.V2) in Brazil

    Authors: Svetoslav N Slavov PhD; Jose Patane PhD; Rafael S Bezerra BSc; Marta Giovanetti PhD; Vagner Fonseca MSc; Antonio J Martins PhD; Vincent L Viala PhD; Evandra S Rodrigues PhD; Elaine V Santos PhD; Claudia R.S Barros PhD; Elaine C Marqueze PhD; Bibiana Santos MSc; Flavia Aburjaile PhD; Raul M Neto PhD; Debora B Moretti PhD; Ricardo Haddad MSc; Rodrigo T Calado PhD; Joao Paulo Kitajima PhD; Erika Freitas PhD; David Schlesinger PhD; Luiz C.J Alcantara PhD; M. Carolina Elias PhD; Sandra C.S Vessoni PhD; Simone Kashima PhD; Dimas T Covas Md-PhD

    doi:10.1101/2021.03.30.21254591 Date: 2021-04-04 Source: medRxiv

    Sao Paulo State, the most populous area in Brazil, currently experiences a second wave of the COVID-19 pandemic MESHD which overwhelmed the healthcare system. Recently, due to the paucity of SARS-CoV-2 MESHD complete genome sequences, we established a Network for Pandemic Alert of Emerging SARS-CoV-2 Variants to rapidly understand the spread of SARS-CoV-2 and monitor in nearly real-time the circulating SARS-CoV-2 variants into the state. Through full genome analysis of 217 SARS-CoV-2 complete genome sequences obtained from the largest regional health departments we were able to identify the co-circulation of multiple SARS-CoV-2 lineages such as i) B.1.1 (0.92%), ii) B.1.1.1 (0.46%), iii) B.1.1.28 (25.34%), iv) B.1.1.7 (5.99%), v) B.1.566 (1.84%), vi) P.1 (64.05%), and P.2 (0.92%). Further our analysis allowed the detection, for the first time in Brazil of the South African variant of concern (VOC), the B.1.351 (501Y.V2) (0.46%). The identified lineage was characterized by the presence of the following mutations: ORF1ab PROTEIN: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; Spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F; ORF3a PROTEIN: Q57H, S171L, E: P71L; ORF7b PROTEIN: Y10F, N: T205I; ORF14: L52F. Origin of the most recent common ancestor of this genomic variant was inferred to be between middle October to late December 2020. Analysis of generated sequences demonstrated the predominance of the P.1 lineage and allowed the early detection of the South African strain for the first time in Brazil. Our findings highlight the importance to increase active monitoring to ensure the rapid detection of new SARS-CoV-2 variants with a potential impact in pandemic control and vaccination strategies.

    An immunoinformatics approach to study the epitopes contributed by Nsp13 of SARS-CoV-2

    Authors: Sushant Kumar; Gajendra Kumar Azad

    doi:10.1101/2021.04.02.438155 Date: 2021-04-02 Source: bioRxiv

    The on-going coronavirus disease-19 MESHD ( COVID-19 MESHD) pandemic caused by SARS-CoV-2 has infected hundreds of millions of people and killed more than two million people worldwide. Currently, there are no effective drugs available for treating SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs; however, vaccines are now being administered worldwide to control this virus. In this study, we have studied SARS-CoV-2 helicase, Nsp13, which is critical for viral replication. We compared the Nsp13 sequences reported from India with the first reported sequence from Wuhan province, China to identify and characterize the mutations occurring in this protein. To correlate the functional impact of these mutations, we characterised the most prominent B cell and T cell epitopes contributed by Nsp13. Our data revealed twenty-one epitopes, which exhibited high antigenicity, stability and interactions with MHC class-I and class-II molecules. Subsequently, the physiochemical properties of these epitopes were also analysed. Furthermore, several of these Nsp13 epitopes harbour mutations, which were further characterised by secondary structure and per-residue disorderness MESHD, stability and dynamicity predictions. Altogether, we report the candidate epitopes of Nsp13 that may help the scientific community to understand the evolution of SARS-CoV-2 variants and their probable implications.

    Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites

    Authors: David Hoffmann; Stefan Mereiter; Yoo Jin Oh; Vanessa Monteil; Rong Zhu; Daniel Canena; Lisa Hain; Elisabeth Laurent; Clemens Gruber; Maria Novatchkova; Melita Ticevic; Antoine Chabloz; Gerald Wirnsberger; Astrid Hagelkrueys; Friedrich Altmann; Lukas Mach; Johannes Stadlmann; Chris Oostenbrink; Ali Mirazimi; Peter Hinterdorfer; Josef M Penninger

    doi:10.1101/2021.04.01.438087 Date: 2021-04-01 Source: bioRxiv

    New SARS-CoV-2 variants are continuously emerging with critical implications for therapies or vaccinations. All 22 N-glycan sites of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN remain highly conserved among the variants B.1.1.7, 501Y.V2 and P.1, opening an avenue for robust therapeutic intervention. Here we used a comprehensive library of mammalian carbohydrate-binding proteins (lectins) to probe critical sugar residues on the full-length trimeric Spike and the receptor binding domain (RBD) of SARS-CoV-2. Two lectins, Clec4g HGNC and CD209c, were identified to strongly bind to Spike. Clec4g HGNC and CD209c binding to Spike was dissected and visualized in real time and at single molecule resolution using atomic force microscopy. 3D modelling showed that both lectins can bind to a glycan within the RBD- ACE2 HGNC interface and thus interferes with Spike binding to cell surfaces. Importantly, Clec4g HGNC and CD209c significantly reduced SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs. These data report the first extensive map and 3D structural modelling of lectin-Spike interactions and uncovers candidate receptors involved in Spike binding and SARS-CoV-2 infections MESHD. The capacity of CLEC4G HGNC and mCD209c lectins to block SARS-CoV-2 viral entry holds promise for pan-variant therapeutic interventions.

    Fine-tuning the Spike: Role of the nature and topology of the glycan shield structure and dynamics of SARS-CoV-2 S MESHD

    Authors: Aoife M Harbison; Carl A Fogarty; Toan K Phung; Akash Satheesan; Benjamin L. Schulz; Elisa Fadda

    doi:10.1101/2021.04.01.438036 Date: 2021-04-01 Source: bioRxiv

    The SARS-CoV-2 spike PROTEIN (S) is a type I fusion glycoprotein, responsible for initiating the infection leading to COVID19 MESHD. As a feature unique of SARS-CoV-2, the thick glycan shield covering the S protein PROTEIN is not only essential for hiding the virus from immune detection, but it also plays multiple functional roles, stabilising the S prefusion open conformation, which is competent for binding the ACE2 primary receptor, and gating the open-to-close transitions. This newly discovered functions of the glycan shield suggest the evolution of its sites of glycosylation is potentially intertwined with the evolution of the overall protein sequence to affect optimal activity. Furthermore, recent studies indicate that the occupancy and structures of SARS-CoV-2 S glycosylation depends MESHD not only on the host-cell, but also on the structural stability of the prefusion trimer; a point that raises important questions about the relative binding competence of different glycoforms. In this work we use multi-microsecond molecular dynamics simulations to characterize the structure and dynamics of different SARS-CoV-2 S MESHD models with different N-glycans at key functional sites, namely N234, N165 and N343. We also assessed the effect of a change in the SARS-CoV-2 S glycan shield topology at N370, due to the recently acquired T372A mutation. Our results indicate that the structures of the N-glycans at N234, N165 and N343 affect the stability of the active (or open) S conformation, and thus its exposure and accessibility. Furthermore, while glycosylation at N370 stabilizes the open S conformation, we find that the N370 glycan binds the closed receptor binding domain (RBD) surface, essentially tying the closed protomers together. These results suggest that the loss of the N370 glycosylation site in SARS-CoV-2 may have increased the availability of the open S form, perhaps contributing to its higher infectivity relative to CoV1 and other variants carrying the sequon. Finally, we discuss these specific changes to the topology of the SARS-CoV-2 S glycan shield through ancestral sequence reconstruction of select SARS strains and discuss how they may have evolved to affect S activity.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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