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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2072)

ProteinN (185)

NSP5 (63)

ProteinS1 (55)

ComplexRdRp (52)


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    First-in-Human Trial of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN Protein Vaccine with Adjuvant of Aluminum Hydroxide and CpG 1018

    Authors: Szu-Min Hsieh; Wang-Da Liu; Yu-Shan Huang; Yi-Jiun Lin; Erh-Fang Hsieh; Wei-Cheng Lian; Charles Chen; I-Chen Tai; Shan-Chwen Chang

    doi:10.1101/2021.03.31.21254668 Date: 2021-04-06 Source: medRxiv

    Design This is a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a recombinant stabilized prefusion SARS-CoV-2 spike PROTEIN ( S-2P HGNC) protein vaccine with adjuvant of aluminum hydroxide and CpG 1018. Methods We enrolled 45 healthy adults from 20 to 49 years of age to be administered with two vaccinations of MVC-COV1901 in a low dose (LD), middle dose (MD), and high dose ( HD MESHD) of spike protein PROTEIN at 28 days apart. There were 15 participants in each dose group, and all of them were followed up for 28 days after the second vaccination at the time of interim analysis. Adverse events (AEs) and laboratory data were recorded for safety evaluation. Blood samples were collected for wild-type SARS-CoV-2 and pseudovirus neutralization assays as well as SARS-CoV-2 spike PROTEIN-specific immunoglobulin G (IgG) at various times. Overall, the study duration will be 7 months. Results Solicited events were mostly mild and similar in the participants of all three dose groups. No subject experienced fever MESHD. There were no serious nor adverse events of special interest at the time point of this interim report. After the second vaccination, the SARS-CoV-2 spike PROTEIN specific IgG titers increased with peak geometric mean titers at 7178.245 (LD), 7746.086 (MD), and 11220.58 ( HD MESHD), respectively. Serum neutralizing activity was detected by two methods in all participants of MD MESHD and HD MESHD groups, with geometric mean values generally comparable to those of a panel of control convalescent serum specimens. All of the participants in the MD MESHD and HD MESHD groups were seroconverted after the second vaccination. Conclusions The MVC-COV1901 vaccine is safe and elicits remarkable immune responses especially in the MD MESHD and HD MESHD groups.

    SARS-CoV-2 Vaccines Elicit Durable Immune Responses in Infant Rhesus Macaques

    Authors: Carolina Garrido Garrado; Alan D Curtis; Maria Dennis; Sachi H Pathak; Hongmei Gao; David Montefiori; Mark Tomai; Christopher B Fox; Pamela A Kozlowski; Trevor Scobey; Jennifer E Munt; Michael L Mallory; Pooja T Saha; Michael G Hudgens; Lisa C Lindesmith; Ralph S. Baric; Olubukola M Abiona; Kizzmekia S Corbett; Darin Edwards; Andrea Carfi; Genevieve Fouda; Koen K. A. Van Rompay; Kristina De Paris; Sallie R Permar

    doi:10.1101/2021.04.05.438479 Date: 2021-04-06 Source: bioRxiv

    Early life SARS-CoV-2 vaccination has the potential to provide lifelong protection and achieve herd immunity. To evaluate SARS-CoV-2 infant vaccination, we immunized two groups of 8 infant rhesus macaques (RMs) at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein PROTEIN, either encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or mixed with 3M-052-SE, a TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. High magnitude S-binding IgG and neutralizing infectious dose 50 (ID50) >103 were elicited by both vaccines. S-specific T cell responses were dominated by IL-17 HGNC, IFN-g HGNC, or TNF-a HGNC. Antibody and cellular responses were stable through week 22. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines are promising pediatric SARS-CoV-2 vaccine candidates to achieve durable protective immunity.

    Therapeutic application of alpha-1-antitrypsin HGNC in COVID-19 MESHD

    Authors: Felix Ritzmann; Praneeth Chitirala; Yiwen Yao; Nadine Krueger; Markus Hoffmann; Wei Zuo; Frank Lammert; Sigrun Smola; Nastasja Seiwert; Naveh Tov; Noga Alagem; Bahareh Mozafari; Katharina Guenther; Martina Seibert; Sabrina Hoersch; Thomas Volk; Philipp M. Lepper; Guy Danziger; Stefan Poehlmann; Christoph Beisswenger; Christian Herr; Robert Bals

    doi:10.1101/2021.04.02.21252580 Date: 2021-04-06 Source: medRxiv

    Rationale: The treatment options for COVID-19 MESHD patients are sparse and do not show sufficient efficacy. Alpha-1-antitrypsin HGNC ( AAT HGNC) is a multi-functional host-defense protein with anti-proteolytic and anti-inflammatory activities. Objectives: The aim of the present study was to evaluate whether AAT HGNC is a suitable candidate for treatment of COVID-19 MESHD. Methods: AAT HGNC and inflammatory markers were measured in the serum of COVID-19 MESHD patients. Human cell cultures were employed to determine the cell-based anti-protease activity of AAT HGNC and to test whether AAT HGNC inhibits the host cell entry of vesicular stomatitis virus MESHD ( VSV MESHD) particles bearing the spike (S) protein PROTEIN of SARS-CoV-2 and the replication of authentic SARS-CoV-2. Inhaled and / or intravenous AAT HGNC was applied to nine patients with mild-to-moderate COVID-19 MESHD. Measurements and Main Results: The serum AAT HGNC concentration in COVID-19 MESHD patients was increased as compared to control patients. The relative AAT HGNC concentrations were decreased in severe COVID-19 MESHD or in non-survivors in ratio to inflammatory blood biomarkers. AAT HGNC inhibited serine protease HGNC activity in human cell cultures, the uptake of VSV MESHD-S into airway cell lines and the replication of SARS-CoV-2 in human lung organoids. All patients, who received AAT HGNC, survived and showed decreasing respiratory distress, inflammatory markers, and viral load. Conclusion: AAT HGNC has anti-SARS-CoV-2 activity in human cell models, is well tolerated in patients with COVID-19 MESHD and together with its anti-inflammatory properties might be a good candidate for treatment of COVID-19 MESHD.

    Murine monoclonal antibodies against RBD of SARS-CoV-2 neutralize authentic wild type SARS-CoV-2 as well as B.1.1.7 and B.1.351 viruses and protect in vivo in a mouse model in a neutralization dependent manner

    Authors: Fatima Amanat; Shirin Strohmeier; Wen-Hsin Lee; Sandhya Bangaru; Andrew B Ward; Lynda Coughlan; Florian Krammer

    doi:10.1101/2021.04.05.438547 Date: 2021-04-06 Source: bioRxiv

    After first emerging in December 2019 in China, severe acute respiratory syndrome MESHD 2 (SARS-CoV-2) has since caused a pandemic leading to millions of infections and deaths worldwide. Vaccines have been developed and authorized but supply of these vaccines is currently limited. With new variants of the virus now emerging and spreading globally, it is essential to develop therapeutics that are broadly protective and bind conserved epitopes in the receptor binding domain (RBD) or the whole spike of SARS-CoV-2 PROTEIN. In this study, we have generated mouse monoclonal antibodies (mAbs) against different epitopes on the RBD and assessed binding and neutralization against authentic SARS-CoV-2. We have demonstrated that antibodies with neutralizing activity, but not non-neutralizing antibodies, lower viral titers in the lungs when administered in a prophylactic setting in vivo in a mouse challenge model. In addition, most of the mAbs cross-neutralize the B.1.351 as well as the B.1.1.7 variants in vitro.

    XAV-19, a novel swine glyco-humanized polyclonal antibody against SARS-CoV-2 spike PROTEIN, efficiently neutralizes B.1.1.7 British and B.1.351 South-African variants.

    Authors: Bernard Vanhove; Benjamin Gaborit; Gwenaelle Evanno; Carine Ciron; Pierre-Joseph Royer; Elsa Lheriteau; Soline Denie; Francois Raffi; Odile Duvaux

    doi:10.1101/2021.04.02.437747 Date: 2021-04-05 Source: bioRxiv

    Amino acid substitutions and deletions in spike (S) protein PROTEIN of the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein PROTEIN, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. We report on XAV-19, a swine glyco-humanized polyclonal antibody (GH-pAb) raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 spike protein PROTEIN of SARS-CoV-2. XAV-19 target epitopes are distributed all over the RBD and particularly cover the receptor binding motives (RBM), on direct contact sites with the Angiotensin Converting Enzyme-2 (ACE-2). Using spike/ACE2 interaction assays, we analyzed in vitro the impact of punctual and grouped mutations in the S protein PROTEIN corresponding to the B.1.1.7 (British form; UK) and B.1.351 (South-African form, SA) variants and recorded that neutralization by XAV-19 exhibited little if any sensitivity to these mutations. These results were confirmed by two independent tissue culture infective doses assays (TCID) showing 100% neutralization of the variants at close concentrations. XAV-19, which is currently evaluated in patients hospitalized for coronavirus disease 2019 MESHD ( Covid-19 MESHD) in the phase 2a-2b of the POLYCOR study (ClinicalTrial.gov, NCT04453384), may provide a novel effective therapeutic tool to combat coronavirus disease 2019 MESHD ( Covid-19 MESHD), caused by the original Wuhan form and by the UK/SA variants of concern.

    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.

    T-cell responses as a correlate of COVID-19 MESHD vaccination. A pilot study in Health Care Workers.

    Authors: Monica Martinez-Gallo; Juliana Esperalba-Ezquerra; Ricardo Pujol-Borrell; Victor Sanda; Iria Arrese-Munoz; Candela Fernandez-Naval; Andres Anton-Pagarolas; Victoria Cardona; Moises Labrador-Horrillo; Tomas Pumarola-Sune; Manuel Hernandez-Gonzalez

    doi:10.1101/2021.03.31.21254472 Date: 2021-04-05 Source: medRxiv

    Background: Clinical trials on the different vaccines to SARS-CoV-2 have demonstrated protection efficacy, but it is urgent to assess the levels of protection generated with real-world data, especially in individuals professionally exposed. Measuring T-cell responses may complement antibody tests currently in use as correlates of protection but there are not validated T-cell responses applicable to large number of samples. Objective: To assess the feasibility of using T-cell responses to SARS-CoV-2 S MESHD peptides by commercially available whole blood interferon-gamma HGNC release assays (IGRA) as a correlate of protection. Patients: Twenty health care workers before and after vaccination. Methods: Antibody test to SARS-CoV-2 N MESHD and S proteins PROTEIN in parallel with one IGRA assay and two detection techniques than can be automated. Results: IGRA test detected T-cell responses in naturally exposed and vaccinated HCW already after first vaccination dose. the correlation by the two detection methods, CLIA and ELISA, very high (R>0.9) and sensitivity and specificity ranged between 100 and 86% and 100-73% respectively. Even though there was a very high concordance between antibody and the IGRA assay in the ability to detect immune response to SARS-CoV-2 there was a relatively low quantitative correlation. In the small group primed by natural infection, one vaccine dose was sufficient to reach immune response plateau. IGRA was positive in one Ig (S) antibody negative vaccinated immunosuppressed HCW illustrating another advantage of the IGRA test. Conclusion: Whole blood IGRA tests amenable to automation, as the one here reported, constitute a promising additional tool for measuring the state of the immune response to SARS-CoV-2; they are applicable to large number of samples and may become valuable correlates of protection to COVID-19 MESHD, particularly for vulnerable groups at risk of being re-exposed to infection, as are health care workers.

    A Rapid SARS-CoV-2 Variant Detection by Molecular-Clamping Based RT-qPCR

    Authors: Shuo Shen; Andrew Y Fu; Maidar Jamba; Jonathan Li; Mike J Powell; Aiguo Zhang; Chuanyi M Lu; Michael Y Sha

    doi:10.1101/2021.04.01.21254484 Date: 2021-04-05 Source: medRxiv

    We applied XNA-based Molecular Clamping Technology to develop a multiplex qPCR assay for rapid and accurate detection of SARS-CoV-2 mutations. A total of 278 previously tested SARS-COV-2 positive samples originating primarily from San Francisco Bay Area were tested, including 139 Samples collected in middle January and 139 samples collected at the end of February 2021, respectively. The SARS-CoV-2 Spike PROTEIN-gene D614G mutation was detected from 58 samples (41.7%) collected in January 2021 and, 78 samples (56.1%) collected in February. Notably, while there were no N501Y mutation detected in samples from January, seven of the February samples were tested positive for the N501Y and D614G mutations. The results suggest a relatively recent and speedy spreading of the UK variant (B.1.1.7) in Northern California. This new Molecular Clamping technology-based multiplex RT-qPCR assay is highly sensitive and specific and can help speed up large scale testing for SARS-CoV-2 variants.

    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.

    Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 MESHD convalescent plasma donors in Wuhan

    Authors: Cesheng Li; Ding Yu; Xiao Wu; Hong Liang; Zhijun Zhou; Yong Xie; Taojing Li; Junzheng Wu; Fengping Lu; Lu Feng; Min Mao; Lianzhen Lin; Huanhuan Guo; Shenglan Yue; Feifei Wang; Yan Peng; Yong Hu; Zejun Wang; Jianhong Yu; Yong Zhang; Jia Lu; Haoran Ning; Huichuan Yang; Daoxing Fu; Yanlin He; Dongbo Zhou; Tao Du; Kai Duan; Demei Dong; Kun Deng; Xia Zou; Ya Zhang; Rong Zhou; Yang Gao; Xinxin Zhang; Xiaoming Yang

    doi:10.1101/2021.04.05.437224 Date: 2021-04-05 Source: bioRxiv

    To investigate the duration of humoral immune response in convalescent coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) patients, we conducted a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and tested specific antibody response. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein PROTEIN (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in the COVID-19 MESHD convalescent plasma donors exceeded 70% for 12 months post diagnosis. RBD-IgG kinetics displayed a gradually downward trend, the titer started to stabilize after 9 months and decreased by 68.1% compared with the 1st month. Moreover, male plasma donors produced more RBD-IgG than female plasma donors and patient age positively correlated with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers was also identified. This study is essential for understanding SARS-CoV-2-induced immune memory to develop vaccine and therapeutics.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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