Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (696)

ProteinN (18)

ProteinS1 (15)

NSP5 (10)

ComplexRdRp (9)


SARS-CoV-2 Proteins
    displaying 1 - 10 records in total 696
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    Spike Protein PROTEIN Targeting "Nano-Glue" that Captures and Promotes SARS-CoV-2 Elimination

    Authors: Guofang Zhang; Yalin Cong; Guoli Cao; Liang Li; Peng Yu; Qingle Song; Ke Liu; Jing Qu; Jing Wang; Wei Xu; Shumin Liao; Yunping Fan; Yufeng Li; Guocheng Wang; Lijing Fang; Yanzhong Chang; Yuliang Zhao; Diana Boraschi; Hongchang Li; Chunying Chen; Liming Wang; Yang Li

    doi:10.1101/2021.04.13.439641 Date: 2021-04-14 Source: bioRxiv

    The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike PROTEIN protein with abundant {beta}-sheet structure serves as target for COVID-19 MESHD therapeutic drug design. Here, we discovered that ultrathin 2D CuInP2S6 (CIPS) nanosheets as a new agent against SARS-CoV-2 infection MESHD, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike PROTEIN protein, with consequent inhibition of virus entry and infection in ACE2 HGNC-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein PROTEIN (KD < 1 pM) with negligible toxicity MESHD in vitro and in vivo. Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.

    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.

    Epitope classification and RBD binding properties of neutralizing antibodies against SARS-CoV-2 variants of concern

    Authors: Ashlesha Deshpande; Bethany D. Harris; Luis Martinez-Sobrido; James J. Kobie; Mark R Walter

    doi:10.1101/2021.04.13.439681 Date: 2021-04-13 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 MESHD (SAR-CoV-2) causes coronavirus disease 2019 MESHD ( COVID19 MESHD) that is responsible for short and long-term disease, as well as death, in susceptible hosts. The receptor binding domain (RBD) of the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN ( S) protein PROTEIN binds to cell surface angiotensin converting enzyme type-II ( ACE2 HGNC) to initiate viral attachment and ultimately viral pathogenesis. The SARS-CoV-2 S RBD MESHD is a major target of neutralizing antibodies (NAbs) that block RBD - ACE2 HGNC interactions. In this report, NAb-RBD binding epitopes in the protein databank were classified as C1, C1D, C2, C3, or C4 HGNC, using a RBD binding profile (BP), based on NAb-specific RBD buried surface area and used to predict the binding epitopes of a series of uncharacterized NAbs. Naturally occurring SARS-CoV-2 RBD sequence variation was also quantified to predict NAb binding sensitivities to the RBD-variants. NAb and ACE2 HGNC binding studies confirmed the NAb classifications and determined whether the RBD variants enhanced ACE2 HGNC binding to promote viral infectivity, and/or disrupted NAb binding to evade the host immune response. Of 9 single RBD mutants evaluated, K417T, E484K, and N501Y disrupted binding of 65% of the NAbs evaluated, consistent with the assignment of the SARS-CoV-2 P.1 Japan/Brazil strain as a variant of concern (VoC). RBD variants E484K and N501Y exhibited ACE2 HGNC binding equivalent to a Wuhan-1 reference SARS-CoV-2 RBD. While slightly less disruptive to NAb binding, L452R enhanced ACE2 HGNC binding affinity. Thus, the L452R mutant, associated with the SARS-CoV-2 California VoC MESHD (B.1.427/B.1.429-California), has evolved to enhance ACE2 HGNC binding, while simultaneously disrupting C1 and C2 NAb classes. The analysis also identified a non-overlapping antibody pair (1213H7 and 1215D1) that bound to all SARS-CoV-2 RBD variants evaluated, representing an excellent therapeutic option for treatment of SARS-CoV-2 WT MESHD and VoC strains.

    Antibody and T-cell responses to a single dose of the AZD1222/Covishield vaccine in previously SARS-CoV-2 infected MESHD and naive health care workers in Sri HGNC Lanka

    Authors: Chandima Jeewandara; Achala Kamaladasa; Pradeep D Pushpakumara; Deshni Jayathilaka; Inoka Sepali; Saubhagyagya Danasekara; Dinuka Guruge; Thushali Ranasinghe; Shashika Dayaratne; Thilagaraj T Padmanadan; Gayasha Somathilaka; Deshan Madusanka; Shyrar Tanussiya; Tibutius Jayadas; Heshan Kuruppu; Ayesha Wijesinghe; Nimasha Thashmi; Dushantha Milroy; Achini Nandasena; Nilanka Sanjeewani; Ruwan Wijayamuni; Sudath Samaraweera; Lisa Schimanski; Tiong Tan; Tao Dong; Graham Ogg; Alain Townsend; Gathsaurie Neelika Malavige

    doi:10.1101/2021.04.09.21255194 Date: 2021-04-13 Source: medRxiv

    Background: In order to determine the immunogenicity of a single dose of the AZD1222/Covishield vaccine in a real-world situation, we assessed the immunogenicity, in a large cohort of health care workers in Sri HGNC Lanka. Methods: SARS-CoV-2 antibodies was carried out in 607 naive and 26 previously infected health care workers (HCWs) 28 to 32 days following a single dose of the vaccine. Haemagglutination test (HAT) for antibodies to the receptor binding domain (RBD) of the wild type virus, B.1.1.7, B.1.351 and the surrogate neutralization assay (sVNT) was carried out in 69 naive and 26 previously infected individuals. Spike protein PROTEIN (pools S1 and S2) specific T cell responses were measured by ex vivo ELISpot IFNg HGNC; assays in 76 individuals. Results: 92.9% of previously naive HCWs seroconverted to a single dose of the vaccine, irrespective of age and gender; and ACE2 HGNC blocking antibodies were detected in 67/69 (97.1%) previously naive vaccine recipients. Although high levels of antibodies were found to the RBD of the wild type virus, the titres for B.1.1.7 and B.1.351 were lower in previously naive HCWs. Ex vivo T cell responses were observed to S1 in 63.9% HCWs and S2 in 31.9%. The ACE2 HGNC blocking titres measured by the sVNT significantly increased (p<0.0001) from a median of 54.1 to 97.9 % of inhibition, in previously infected HCWs and antibodies to the RBD for the variants B.1.1.7 and B.1.351 also significantly increased. Discussion: a single dose of the AZD1222/Covishield vaccine was shown to be highly immunogenic in previously naive individuals inducing antibody levels greater than following natural infection. In infected individuals, a single dose induced very high levels of ACE2 HGNC blocking antibodies and antibodies to RBDs of SARS-CoV-2 variants of concern.

    A multiplexed high-throughput neutralization assay reveals a lack of activity against multiple variants after SARS-CoV-2 infection MESHD

    Authors: Craig Fenwick; Priscilla Turelli; Celine Pellaton; Alex Farina; Jeremy Campos; Charlene Raclot; Florence Pojer; Valeria Cagno; Giuseppe Pantaleo; Didier Trono

    doi:10.1101/2021.04.08.21255150 Date: 2021-04-13 Source: medRxiv

    The detection of SARS-CoV-2-specific antibodies in the serum of an individual indicates prior infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral Spike are far more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, poorly flexible and potentially biohazardous. Here we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein binding to the angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) viral receptor. This high-throughput method matches the performance of the gold standard live virus infectious assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific IgG titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 Spike PROTEIN variants of concern (VOC), which is otherwise unpredictable even in individuals displaying robust neutralizing antibody responses. Profiling serum samples from 59 hospitalized COVID-19 MESHD patients, we found that although most had high activity against the 2019-nCoV Spike and to a lesser extent the B.1.1.7 variant, only 58% could efficiently neutralize a Spike derivative containing mutations present in the B.1.351 variant. In conclusion, we have developed an assay that has proven its clinical relevance in the large-scale evaluation of effective neutralizing antibody responses to VOC after natural infection and that can be applied to the characterization of vaccine-induced antibody responses and of the potency of human monoclonal antibodies.

    Prediction and evolution of the molecular fitness of SARS-CoV-2 variants: Introducing SpikePro

    Authors: Fabrizio Pucci; Marianne Rooman

    doi:10.1101/2021.04.11.439322 Date: 2021-04-12 Source: bioRxiv

    The understanding of the molecular mechanisms driving the fitness of the SARS-CoV-2 MESHD virus and its mutational evolution is still a critical issue. We built a simplified computational model, called SpikePro, to predict the SARS-CoV-2 fitness MESHD from the amino acid sequence and structure of the spike protein PROTEIN. It contains three contributions: the viral transmissibility predicted from the stability of the spike protein PROTEIN, the infectivity computed in terms of the affinity of the spike protein PROTEIN for the ACE2 HGNC receptor, and the ability of the virus to escape from the human immune response based on the binding affinity of the spike protein PROTEIN for a set of neutralizing antibodies. Our model reproduces well the available experimental, epidemiological and clinical data on the impact of variants on the biophysical characteristics of the virus. For example, it is able to identify circulating viral strains that, by increasing their fitness, recently became dominant at the population level. SpikePro is a useful instrument for the genomic surveillance of the SARS-CoV-2 virus, since it predicts in a fast and accurate way the emergence of new viral strains and their dangerousness. It is freely available in the GitHub repository

    Ultrastructural insight into SARS-CoV-2 attachment, entry and budding in human airway epithelium

    Authors: Andreia L Pinto; Ranjit K Rai; Jonathan C Brown; Paul Griffin; James R Edgar; Anand Shah; Aran Singanayagam; Claire Hogg; Wendy S Barclay; Clare E Futter; Thomas Burgoyne

    doi:10.1101/2021.04.10.439279 Date: 2021-04-11 Source: bioRxiv

    Ultrastructural studies of SARS-CoV-2 infected MESHD cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Many studies are limited by the lack of access to appropriate cellular models. As the airway epithelium is the primary site of infection it is essential to study SARS-CoV-2 infection MESHD of these cells. Here, we examined human airway epithelium, grown as highly differentiated air-liquid interface cultures and infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant (Variant of Concern 202012/01) by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Two key SARS-CoV-2 entry molecules, ACE2 HGNC and TMPRSS2 HGNC, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistent with these observations, extracellular virions were frequently seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion at the apical plasma membrane demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein PROTEIN-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein PROTEIN. Profiles strongly suggesting viral budding from the membrane was observed in these compartments and this may explain how virions gain their S glycoprotein PROTEIN containing envelope.

    Atypical N-glycosylation of SARS-CoV-2 impairs MESHD the efficient binding of Spike- RBM HGNC to the human-host receptor hACE2

    Authors: Gustavo Gamez; Juan A Hermoso; Cesar Carrasco-Lopez; Alejandro Gomez Mejia; Carlos Muskus; Sven Hammerschmidt

    doi:10.1101/2021.04.09.439154 Date: 2021-04-10 Source: bioRxiv

    SARS-CoV-2 internalization by human host cells relies on the molecular binding of its spike glycoprotein PROTEIN (SGP) to the angiotensin-converting-enzyme-2 HGNC (hACE2) receptor. It remains unknown whether atypical N-glycosylation of SGP modulates SARS-CoV-2 tropism for infections MESHD. Here, we address this question through an extensive bioinformatics analysis of publicly available structural and genetic data. We identified two atypical sequons (sequences of N-glycosylation: NGV 481-483 and NGV 501-503), strategically located on the receptor-binding motif ( RBM HGNC) of SGP and facing the hACE2 HGNC receptor. Interestingly, the cryo-electron microscopy structure of trimeric SGP in complex with potent-neutralizing antibodies from convalescent patients revealed covalently-linked N-glycans in NGV 481-483 atypical sequons. Furthermore, NGV 501-503 atypical sequon involves the asparagine-501 residue, whose highly-transmissible mutation N501Y is present in circulating variants of major concerns and affects the SGP- hACE2 HGNC binding-interface through the well-known hotspot-353. These findings suggest that atypical SGP post-translational modifications modulate the SGP- hACE2 HGNC binding-affinity affecting consequently SARS-CoV-2 transmission and pathogenesis.

    Intranasal HD MESHD-Ad Vaccine Protects the Upper and Lower Respiratory Tracts of hACE2 HGNC Mice against SARS-CoV-2

    Authors: Huibi Cao; Juntao Mai; Zhichang Zhou; Zhijie Li; Rongqi Duan; Jacqueline Watt; Ziyan Chen; Ranmal Avinash Bandara; Ming Li; Sang Kyun Ahn; Betty Boon; Natasha Christie; Scott Gray-Owen; Rob Kozak; Samira Mubareka; James M Rini; Jim Hu; Jun Liu

    doi:10.1101/2021.04.08.439006 Date: 2021-04-09 Source: bioRxiv

    The COVID-19 pandemic MESHD has affected more than 120 million people and resulted in over 2.8 million deaths worldwide. Several COVID-19 MESHD vaccines have been approved for emergency use in humans and are being used in many countries. However, all of the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection MESHD or viral transmission. Here, we describe intranasal immunization of a COVID-19 MESHD vaccine delivered by a novel platform, the helper-dependent adenoviral ( HD MESHD-Ad) vector. Since HD MESHD-Ad vectors are devoid of adenoviral coding sequences, they have a superior safety profile and a large cloning capacity for transgenes. The vaccine ( HD MESHD-Ad_RBD) codes for the receptor binding domain (RBD) of the SARS-CoV-2 spike PROTEIN protein and intranasal immunization induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18- hACE2 HGNC mice with HD MESHD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection MESHD. As such, intranasal immunization based on the HD MESHD-Ad vector promises to provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.

    A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 MESHD spike protein PROTEIN to ACE2

    Authors: Kaleb B Tsegay; Christiana M Adeyemi; Edward P Gniffke; John K Walker; Stephen E.P. Smith

    doi:10.1101/2021.04.08.439071 Date: 2021-04-08 Source: bioRxiv

    Repurposed drugs that block the interaction between the SARS-CoV-2 spike PROTEIN protein and its receptor ACE2 HGNC could offer a rapid route to novel COVID-19 MESHD treatments or prophylactics. Here, we screened 2701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike PROTEIN protein to recombinant human ACE2 HGNC. We identified 56 compounds that inhibited binding by <90%, measured the EC50 of binding inhibition, and computationally modeled the docking of the best inhibitors to both Spike and ACE2 HGNC. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike- ACE2 HGNC interaction as well as identifying several potential inhibitors that could serve as templates for future drug discovery efforts.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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