Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (514)

NSP5 (30)

ProteinN (27)

ProteinS1 (21)

ComplexRdRp (21)


SARS-CoV-2 Proteins
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    Clinicopathologic features of a feline SARS-CoV-2 infection MESHD model parallel acute COVID-19 MESHD in humans

    Authors: Jennifer Rudd; Miruthula Tamil Selvan; Shannon Cowan; Cecily Midkiff; Jerry Ritchey; Craig A Miller

    doi:10.1101/2021.04.14.439863 Date: 2021-04-14 Source: bioRxiv

    The emergence and ensuing dominance of COVID-19 MESHD on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics and assessment of immune responses to SARS-CoV-2 infection MESHD. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease MESHD, divergence from clinical COVID-19 MESHD disease, and requirements for host genetic modifications to permit infection. This study validates a feline model for SARS-CoV-2 infection MESHD that results in clinical disease and histopathologic lesions consistent with severe COVID-19 MESHD in humans. Intra-tracheal inoculation of concentrated SARS-CoV-2 caused infected cats to develop clinical disease consistent with that observed in the early exudative phase of COVID-19 MESHD. A novel clinical scoring system for feline respiratory disease MESHD was developed and utilized, documenting a significant degree of lethargy MESHD, fever MESHD, dyspnea MESHD, and dry cough in infected MESHD cats. In addition, histopathologic pulmonary lesions MESHD such as diffuse alveolar damage MESHD, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were observed due to SARS-CoV-2 infection MESHD, imitating lesions identified in people hospitalized with ARDS from COVID-19 MESHD. A significant correlation exists between the degree of clinical disease identified in infected cats and pulmonary lesions MESHD. Viral loads and ACE2 expression were quantified in nasal turbinates, distal trachea, lung, and various other organs. Natural ACE2 HGNC expression, paired with clinicopathologic correlates between this feline model and human COVID-19 MESHD, encourage use of this model for future translational studies.

    Neuropilin-1 HGNC Mediates SARS-CoV-2 Infection MESHD in Bone Marrow-derived Macrophages

    Authors: Gao Junjie; Mei Hong; Sun Jing; Li Hao; Huang Yuege; Tang Yanhong; Duan Linwei; Liu Delin; Wang Qiyang; Gao Youshui; Song Ke; Zhao Jincun; Zhang Changqing; Liu Jia

    doi:10.1101/2021.04.14.439793 Date: 2021-04-14 Source: bioRxiv

    SARS-CoV-2 infection MESHD in human can cause medical complications across various tissues and organs. Despite of the advances to understanding the pathogenesis of SARS-CoV-2, its tissue tropism and interactions with host cells have not been fully understood. Existing clinical data have suggested possible SARS-CoV-2 infection MESHD in human skeleton system. In the present study, we found that authentic SARS-CoV-2 could efficiently infect human and mouse bone marrow-derived macrophages (BMMs) and alter the expression of macrophage chemotaxis and osteoclast-related genes. Importantly, in a mouse SARS-CoV-2 infection MESHD model that was enabled by the intranasal adenoviral (AdV) delivery of human angiotensin converting enzyme 2 HGNC ( hACE2 HGNC), SARS-CoV-2 was found to be present in femoral BMMs as determined by in situ immunofluorescence analysis. Using single-cell RNA sequencing (scRNA-Seq), we characterized SARS-CoV-2 infection MESHD in BMMs. Importantly, SARS-CoV-2 entry on BMMs appeared to be dependent on the expression of neuropilin-1 HGNC ( NRP1 HGNC) rather than the widely recognized receptor ACE2 HGNC. It was also noted that unlike brain macrophages which displayed aging-dependent NRP1 expression, BMMs from neonatal and aged mice had constant NRP1 expression, making BMMs constantly vulnerable target cells for SARS-CoV-2. Furthermore, it was found that the abolished SARS-CoV-2 entry in BMM-derived osteoclasts was associated with the loss of NRP1 expression during BMM-to-osteoclast differentiation. Collectively, our study has suggested that NRP1 HGNC can mediate SARS-CoV-2 infection MESHD in BMMs, which precautions the potential impact of SARS-CoV-2 infection MESHD on human skeleton system.

    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.

    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.

    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.

    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.

    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.

    The homology analysis of ACE2 HGNC gene and its distinct expression in laboratory and wild animals

    Authors: Gang Wang; Zhang A-Mei; Wang Binghui; Jianhua Yin; Feng Yue; Zulqarnain Baloch; Xue-shan Xia

    doi:10.1101/2021.04.08.439088 Date: 2021-04-10 Source: bioRxiv

    Angiotensin-converting enzyme-2 ( ACE2 HGNC) has been recognized as an entry receptor of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) into the host cells while bats has been suspected as natural host of SARS-CoV-2. However, the detail of intermediate host or the route of transmission of SARS-CoV-2 is still unclear. In this study, we analyze the conservation of ACE2 HGNC gene in 11 laboratory and wild animals that live in close proximity either with Bats or human and further investigated its RNA and protein expression pattern in wild bats, mice and tree shrew. We verified that the wild-bats and mice were belonged to Hipposideros pomona and Rattus norvegicus, respectively. ACE2 gene is highly conserved among all 11 animals species at the DNA level. Phylogenetic analysis based on the ACE2 HGNC nucleotide sequences revealed that wild bat and Tree shrew were forming a cluster close to human. We further report that ACE2 HGNC RNA expression pattern is highly species-specific in different tissues of different animals. Most notably, we found that the expression pattern of ACE2 HGNC RNA and protein are very different in each animal species. In summary, our results suggested that ACE2 HGNC gene is highly conserved among all 11 animals species. However, different relative expression pattern of ACE2 HGNC RNA and protein in each animal species is interesting. Further research is needed to clarify the possible connection between different relative expression pattern of ACE2 HGNC RNA and protein in different laboratory and wild animal species and the susceptibility to SARS-CoV-2 infection MESHD.

    Exploring zebrafish larvae as a COVID-19 MESHD model: probable SARS-COV-2 replication in the swim bladder

    Authors: Valerio Laghi; Veronica Rezelj; Laurent Boucontet; Pierre Boudinot; Irene Salinas; Georges Lutfalla; Marco Vignuzzi; Jean-Pierre Levraud

    doi:10.1101/2021.04.08.439059 Date: 2021-04-10 Source: bioRxiv

    Animal models are essential to understand COVID-19 MESHD pathophysiology and for pre-clinical assessment of drugs and other therapeutic or prophylactic interventions. We explored the small, cheap and transparent zebrafish larva as a potential host for the SARS-CoV-2 virus. Bath exposure, as well as microinjection in the coelom, pericardium, brain ventricle, bloodstream, or yolk, did not result in detectable SARS-CoV-2 replication in wild-type larvae. However, when the virus was inoculated in the swim bladder, a modest increase in viral RNA was observed after 24 hours, suggesting a successful infection in some animals. The low infectivity of SARS- CoV-2 in zebrafish was not due to the host type I interferon response, as similar results were observed in type I interferon-deficient animals. We could not detect the induction of transcriptional type I interferon or inflammatory cytokine responses following infection. Overexpression of human ACE2 HGNC in a mosaic fashion by plasmid injection in eggs was not sufficient to increase SARS-CoV-2 infectivity MESHD. In conclusion, wild-type zebrafish larvae appear mostly non-permissive to SARS-CoV-2, except in the swim bladder, an aerial organ sharing similarities with lungs.

    Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry MESHD

    Authors: Shiyou Zhu; Ying Liu; Zhuo Zhou; Zhiying Zhang; Xia Xiao; Zhiheng Liu; Ang Chen; Xiaojing Dong; Feng Tian; Shihua Chen; Yiyuan Xu; Chunhui Wang; Qiheng Li; Xuran Niu; Qian Pan; Shuo Du; Junyu Xiao; Jianwei Wang; Wensheng Wei

    doi:10.1101/2021.04.08.438924 Date: 2021-04-09 Source: bioRxiv

    The ongoing pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects MESHD a variety of tissues where the known receptor ACE2 HGNC is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection MESHD. In addition to known host proteins, i.e PROTEIN. ACE2 HGNC, TMPRSS2 HGNC, and NRP1 HGNC, we identified multiple host components, among which LDLRAD3 HGNC, TMEM30A HGNC, and CLEC4G HGNC were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain ( NTD HGNC). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 HGNC and CLEC4G HGNC mediate SARS-CoV-2 entry MESHD and infection in a fashion independent of ACE2 HGNC. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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