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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (1507)

ProteinN (152)

NSP5 (53)

ComplexRdRp (41)

ProteinS1 (38)


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SARS-CoV-2 Proteins
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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.

    GRAd-COV2, a gorilla adenovirus based candidate vaccine against COVID-19 MESHD, is safe and immunogenic in young and older adults

    Authors: Simone Lanini; Stefania Capone; Andrea Antinori; Stefano Milleri; Emanuele Nicastri; Roberto Camerini; Chiara Agrati; Concetta Castilletti; Federica Mori; Alessandra Sacchi; Giulia Matusali; Roberta Gagliardini; Virginia Ammendola; Eleonora Cimini; Fabiana Grazioli; Laura Scorzolini; Federico Napolitano; Maria Maddalena Plazzi; Marco Soriani; Aldo De Luca; Simone Battella; Andrea Sommella; Alessandra Maria Contino; Federica Barra; Michela Gentile; Angelo Raggioli; Youfang Shi; Enrico Girardi; Markus Maeurer; Maria Rosaria Capobianchi; Francesco Vaia; Mauro Piacentini; Guido Kroemer; Alessandra Vitelli; Stefano Colloca; Antonella Folgori; Giuseppe Ippolito

    doi:10.1101/2021.04.10.21255202 Date: 2021-04-13 Source: medRxiv

    Safe and effective vaccines against coronavirus disease 2019 MESHD ( COVID-19 MESHD) are urgently needed to control the ongoing pandemic. Although impressive progress has been made with several COVID-19 MESHD vaccines already approved, it is clear that those developed so far cannot meet the global vaccine demand. We have developed a COVID-19 MESHD vaccine based on a replication-defective gorilla adenovirus expressing the stabilized pre-fusion SARS-CoV-2 Spike PROTEIN protein, named GRAd-COV2. We aimed to assess the safety and immunogenicity of a single-dose regimen of this vaccine in healthy younger and older adults to select the appropriate dose for each age group. To this purpose, a phase 1, dose-escalation, open-label trial was conducted including 90 healthy subjects, (45 aged 18-55 years and 45 aged 65-85 years), who received a single intramuscular administration of GRAd-CoV2 at three escalating doses. Local and systemic adverse reactions were mostly mild or moderate and of short duration, and no serious AE was reported. Four weeks after vaccination, seroconversion to Spike/RBD was achieved in 43/44 young volunteers and in 45/45 older subjects. Consistently, neutralizing antibodies were detected in 42/44 younger age and 45/45 older age volunteers. In addition, GRAd-COV2 induced a robust and Th1-skewed T cell response against the S antigen in 89/90 subjects from both age groups. Overall, the safety and immunogenicity data from the phase 1 trial support further development of this vaccine.

    Immunogenicity of SARS-CoV-2 Vaccine in Dialysis

    Authors: Eduardo Lacson Jr.; Christos P Argyropoulos; Harold J Manley; Gideon Aweh; Andrew I Chin; Loay H Salman; Caroline M Hsu; Doug S Johnson; Daniel E Weiner

    doi:10.1101/2021.04.08.21254779 Date: 2021-04-13 Source: medRxiv

    Abstract Importance: Patients receiving maintenance dialysis patients are at high risk for morbidity and mortality from COVID-19 MESHD. The immunogenicity of SARS-CoV-2 mRNA vaccines is unknown in this vulnerable population where immune compromise is common. Objective: To determine seroresponse to vaccination against SARS-CoV-2 utilizing mRNA vaccines among patients receiving maintenance dialysis. Design: Retrospective observational study. Setting: Dialysis Clinic, Inc. (DCI) outpatient dialysis clinics in the United States. Participants: All patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with SARS-CoV-2 spike PROTEIN-antibody test results drawn at least 14 days after the second dose, as documented in the electronic health record through March 18, 2021. Exposure: Two doses of BNT162b2/Pfizer or of mRNA-1273/Moderna vaccines administered per manufacturer recommendations. Main Outcomes and Measures: Levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike PROTEIN antigen (seropositive: 2 or greater) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G). The DCI clinical protocol for in-clinic administration included baseline and follow-up levels although initial administration of the vaccine occurred primarily elsewhere (e.g. long-term care facilities, hospitals, etc.) during the evaluation period. Hence, only post-vaccination antibody levels were reported. Results: Among 186 patients receiving maintenance dialysis from 32 clinics in 8 states tested an average of 23 days after receiving 2 vaccine doses, mean age was 68 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 MESHD history, seropositive rate was 38/38 (100%) with 97% at maximum titer. Conclusions and Relevance: Most patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 MESHD develop robust antibody response. These results support an equitable and aggressive vaccination strategy for all eligible patients receiving maintenance dialysis, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 MESHD in this high risk population.

    Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

    Authors: Kai Wu; Angela Choi; Matthew Koch; Sayda Elbashir; LingZhi Ma; Diana Lee; Angela Woods; Carole Henry; Charis Palandjian; Anna Hill; Julian Quinones; Naveen Nunna; Adrian B McDermott; Samantha Falcone; Elisabeth Narayanan; Tonya Colpitts; Hamilton Bennett; Kizzmekia Corbett; Robert Seder; Barney S Graham; Guillaume BE Stewart-Jones; Andrea Carfi; Darin K Edwards

    doi:10.1101/2021.04.13.439482 Date: 2021-04-13 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the causative agent of a global pandemic that has led to more than 2.8 million deaths worldwide. Safe and effective vaccines are now available, including Moderna's COVID-19 MESHD vaccine (mRNA-1273) that showed 94% efficacy in prevention of symptomatic COVID-19 MESHD disease in a phase 3 clinical study. mRNA-1273 encodes for a prefusion stabilized full length spike (S) protein PROTEIN of the Wuhan-Hu-1 isolate. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several emerging variants have shown decreased susceptibility to neutralization by vaccine induced immunity, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of two updated COVID-19 MESHD mRNA vaccines designed to target emerging SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the S protein PROTEIN found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with 2-doses of mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization in mice. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are currently being evaluated in additional pre-clinical challenge models and in phase 1/2 clinical studies.

    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.

    Impairment of SARS-CoV-2 spike PROTEIN glycoprotein maturation and fusion activity by the broad-spectrum anti-infective drug nitazoxanide

    Authors: Anna Riccio; Silvia Santopolo; Antonio Rossi; Sara Piacentini; Jean-Francois Rossignol; Maria Gabriella Santoro

    doi:10.1101/2021.04.12.439201 Date: 2021-04-12 Source: bioRxiv

    The emergence of the highly-pathogenic severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2), the causative agent of COVID-19 MESHD (coronavirus disease-2019), has caused an unprecedented global health crisis, as well as societal and economic disruption. The SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S), a surface-anchored trimeric class-I fusion glycoprotein essential for entry into host cells, represents a key target for developing vaccines and therapeutics capable of blocking virus invasion. The emergence of several SARS-CoV-2 spike PROTEIN variants that facilitate virus spread and may affect the efficacy of recently developed vaccines, creates great concern and highlights the importance of identifying antiviral drugs to reduce SARS-CoV-2-related morbidity and mortality. Nitazoxanide, a thiazolide originally developed as an antiprotozoal agent with recognized broad-spectrum antiviral activity in-vitro and in clinical studies, was recently shown to be effective against several coronaviruses, including SARS-CoV-2. Using biochemical and pseudovirus entry assays, we now demonstrate that nitazoxanide interferes with the SARS-CoV-2 spike PROTEIN biogenesis, hampering its maturation at an endoglycosidase H-sensitive stage, and hindering its fusion activity in human cells. Besides membrane fusion during virus entry, SARS-CoV-2 S-proteins MESHD S-proteins PROTEIN in infected cells can also trigger receptor-dependent formation of syncytia, observed in-vitro and in COVID-19 MESHD patients tissues, facilitating viral dissemination between cells and possibly promoting immune evasion. Utilizing two different quantitative cell-cell fusion assays, we show that nitazoxanide is effective in inhibiting syncytia formation mediated by different SARS-CoV-2 spike PROTEIN variants in human lung, liver and intestinal cells. The results suggest that nitazoxanide may represent a useful tool in the fight against COVID-19 MESHD infections, inhibiting SARS-CoV-2 replication and preventing spike-mediated syncytia formation.

    Combinatorial approach with mass spectrometry and lectin microarray dissected glycoproteomic features of virion-derived spike protein PROTEIN of SARS-CoV-2

    Authors: Takahiro Hiono; Azusa Tomioka; Hiroyuki Kaji; Michihito Sasaki; Yasuko Orba; Hirofumi Sawa; Atsushi Kuno

    doi:10.1101/2021.04.10.439300 Date: 2021-04-12 Source: bioRxiv

    The COVID-19 pandemic MESHD caused by the novel coronavirus, SARS-CoV-2, has a global impact on public health. Since glycosylation of the viral envelope glycoproteins is known to be deeply associated with their immunogenicity, intensive studies on the glycans of its major glycoprotein, S PROTEIN protein, have been conducted. Nevertheless, the detailed site-specific glycan compositions of virion-associated S protein PROTEIN have not yet been clarified. Here, we conducted intensive glycoproteomic analyses of SARS-CoV-2 S protein PROTEIN using a combinatorial approach with two different technologies: mass spectrometry (MS) and lectin microarray. Using our unique MS1-based glycoproteomic technique, Glyco-RIDGE, in addition to MS2-based Byonic search, we identified 1,759 site-specific glycan compositions. The most frequent was HexNAc:Hex:Fuc:NeuAc:NeuGc = 6:6:1:0:0, suggesting a tri-antennary N-glycan terminating with LacNAc and having bisecting GlcNAc and a core fucose, which was found in 20 of 22 glycosylated sites. The subsequent lectin microarray analysis emphasized intensive outer arm fucosylation of glycans, which efficiently complemented the glycoproteomic features. The present results illustrate the high-resolution glycoproteomic features of SARS-CoV-2 S protein MESHD S protein PROTEIN and significantly contribute to vaccine design, as well as the understanding of viral protein synthesis.

    Revealing the threat of emerging SARS-CoV-2 mutations to antibody therapies

    Authors: Jiahui Chen; Kaifu Gao; Rui Wang; Guo-Wei Wei

    doi:10.1101/2021.04.12.439473 Date: 2021-04-12 Source: bioRxiv

    The ongoing massive vaccination and the development of effective intervention offer the long-awaited hope to end the global rage of the COVID-19 pandemic MESHD. However, the rapidly growing SARS-CoV-2 variants might compromise existing vaccines and monoclonal antibody (mAb) therapies. Although there are valuable experimental studies about the potential threats from emerging variants, the results are limited to a handful of mutations and Eli Lilly and Regeneron mAbs. The potential threats from frequently occurring mutations on the SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN receptor-binding domain (RBD) to many mAbs in clinical trials are largely unknown. We fill the gap by developing a topology-based deep learning strategy that is validated with tens of thousands of experimental data points. We analyze 261,348 genome isolates from patients to identify 514 non-degenerate RBD mutations and investigate their impacts on 16 mAbs in clinical trials. Our findings, which are highly consistent with existing experimental results about variants from the UK, South Africa, Brazil, US-California, and Mexico shed light on potential threats of 95 high-frequency mutations to mAbs not only from Eli Lilly and Regeneron but also from Celltrion and Rockefeller University that are in clinical trials. We unveil, for the first time, that high-frequency mutations R346K/S, N439K, G446V, L455F, V483F/A, E484Q/V/A/G/D, F486L, F490L/V/S, Q493L, and S494P/L might compromise some of mAbs in clinical trials. Our study gives rise to a general perspective about how mutations will affect current vaccines.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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