Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (534)

NSP5 (31)

ProteinN (27)

ProteinS1 (22)

ComplexRdRp (21)


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SARS-CoV-2 Proteins
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    Infants are more susceptible to COVID-19 MESHD than children

    Authors: Char Leung

    doi:10.1101/2021.05.02.21256474 Date: 2021-05-05 Source: medRxiv

    Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) has been found to mediate the host cell entry of SARS-CoV-2 that causes COVID-19 MESHD. However, the link between ACE2 HGNC and the observed susceptibility of SARS-CoV-2 infection MESHD remains elusive. In contrast, observational studies can help identify the susceptibility biomarker of SARS-CoV-2 infection MESHD, those associated with age for example. Data of all PCR tests performed in the state of Sao Paulo of Brazil were gathered from the government database and were analyzed using multivariate logistic regression. Adjusted odds ratios for positive test results were calculated with the adjustment of age, gender, and comorbidities. Over 1.7 million test results were included in the study of which 38% were positive. Elderly was most vulnerable to SARS-CoV-2 infection MESHD. While underages were less susceptible than adults aged below 60 years, susceptibility was not equal among different pediatric groups. It is found that age and susceptibility to SARS-CoV-2 infection MESHD are not inversely related, but U-shaped, with infants more susceptible than children. Biomarkers that are linearly associated with age cannot explain the reduced susceptibility in children. These include lymphocyte count and cross-reactive antibodies against other coronaviruses that offers cross-protection. The expression level of ACE2 HGNC may still be able to explain but further investigations are needed.

    Investigating the relationship between serum ACE 2 HGNC level and COVID-19 MESHD patients' prognosis: a cross-sectional study

    Authors: Parsa Mohammadi; Hesam Aldin Varpaei; Arash Seifi; Sepideh Zahak Miandoab; Saba Beiranvand; Sahar Mobaraki; Mostafa Mohammadi

    doi:10.1101/2021.05.02.21256329 Date: 2021-05-05 Source: medRxiv

    Background: The only known receptor for this virus in the human body is ACE2 HGNC, the same known receptor for the SARS virus. Material and Method: In this single-center cross-sectional study, 38 hospitalized adult ([≥]18 years) patients with laboratory-confirmed COVID-19 MESHD were identified in the infectious disease MESHD ward in Imam Khomeini hospital complex. The study also has been approved in ethics committee of Tehran University of medical sciences with ethic code: 99/11/101/16529. Data were analyzed using SPSS 25. p < 0.05 was considered statistically significant when a two-tailed test was performed. Result: Among the 38 patients, the mean age was 64.13 years, 52.6% were male, 42% were PCR test positive and 39.5% was expired. The most common presenting symptoms were cough MESHD (80%), fever MESHD (75.5%), dyspnea MESHD (60.5%), myalgias MESHD (35.8%), diarrhea MESHD (20%), and nausea MESHD and vomiting MESHD (15%). There were not any significant differences between expired and discharged group in terms of serum ACE2 HGNC level. Results were similar between discharged and expired patients in the subgroup analysis of 38 patients. Conclusion: It seems that serum ACE 2 HGNC level is not correlated with COVID-19 MESHD patients' prognosis. However, it seems that more researches are required to confirm supposed association between serum ACE2 HGNC level and inflammatory biomarkers, clinical outcome, and patient's survival.

    Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 MESHD patient: a source of immune escape variants

    Authors: Sebastian Weigang; Jonas Fuchs; Gert Zimmer; Daniel Schnepf; Lisa Kern; Julius Beer; Hendrik Luxenburger; Jakob Ankerhold; Valeria Falcone; Janine Kemming; Maike Hofmann; Robert Thimme; Christoph Neumann-Haefelin; Svenja Ulferts; Robert Grosse; Daniel Hornuss; Yakup Tanriver; Siegbert Rieg; Dirk Wagner; Daniela Huzly; Martin Schwemmle; Marcus Panning; Georg Kochs

    doi:10.1101/2021.04.30.21256244 Date: 2021-05-05 Source: medRxiv

    The recent emergence of SARS-CoV-2 variants showing increased transmissibility and immune escape is a matter of global concern. Their origin remains unclear, but intra-host virus evolution during persistent infections could be a contributing factor. Here, we studied the long-term SARS-CoV-2 infection MESHD in an immunosuppressed kidney transplant recipient. Frequent respiratory specimens were tested for variant viral genomes by RT-qPCR, next-generation sequencing (NGS), and virus isolation. Late in infection, several virus variants emerged which escaped neutralization by COVID-19 MESHD convalescent and vaccine-induced antisera and had acquired genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil. Importantly, infection of susceptible hACE2 HGNC-transgenic mice with one of the patient escape variants elicited protective immunity against re-infection with either the parental virus, the escape variant or the South African variant of concern, demonstrating broad immune control. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results indicate that immunocompromised patients are an alarming source of potentially harmful SARS-CoV-2 variants and open up new avenues for the updating of COVID-19 MESHD vaccines.

    SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination

    Authors: Markus Hoffmann; Heike Hofmann-Winkler; Nadine Krueger; Amy Kempf; Inga Nehlmeier; Luise Graichen; Anzhalika Sidarovich; Anna-Sophie Moldenhauer; Martin S. Winkler; Sebastian Schulz; Hans-Martin Jaeck; Metodi V. Stankov; Georg M. N. Behrens; Stefan Poehlmann

    doi:10.1101/2021.05.04.442663 Date: 2021-05-05 Source: bioRxiv

    The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic MESHD. The number of COVID-19 MESHD cases and deaths MESHD in India has risen steeply in recent weeks and a novel SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein PROTEIN of B.1.617 harbors two mutations in the receptor binding domain, which interacts with the ACE2 HGNC receptor and constitutes the main target of neutralizing antibodies. Therefore, we analyzed whether B.1.617 is more adept in entering cells and/or evades antibody responses. B.1.617 entered two out of eight cell lines tested with slightly increased efficiency and was blocked by entry inhibitors. In contrast, B.1.617 was resistant against Bamlanivimab, an antibody used for COVID-19 MESHD treatment. Finally, B.1.617 evaded antibodies induced by infection or vaccination, although with moderate efficiency. Collectively, our study reveals that antibody evasion of B.1.617 may contribute to the rapid spread of this variant.

    Combination Respiratory Vaccine Containing Recombinant SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD and QuadrivalentSeasonal Influenza Hemagglutinin Nanoparticles with Matrix-M Adjuvant

    Authors: Micheal J Massare; Nita Patel; Bin Zhou; Sonia Maciejewski; Rhonda Flores; Mimi Guebre-Xabier; Jing-Hui Tian; Alyse D Portnoff; Louis Fries; Vivek Shinde; Larry R Ellingsworth; Greg Glenn; Gale Smith

    doi:10.1101/2021.05.05.442782 Date: 2021-05-05 Source: bioRxiv

    The 2019 outbreak of a severe respiratory disease MESHD caused by an emerging coronavirus, SARS-CoV-2, has spread globally with high morbidity and mortality. Co-circulating seasonal influenza has greatly diminished recently, but expected to return with novel strains emerging, thus requiring annual strain adjustments. We have developed a recombinant hemagglutinin (HA) quadrivalent nanoparticle influenza vaccine (qNIV) produced using an established recombinant insect cell expression system to produce nanoparticles. Influenza qNIV adjuvanted with Matrix-M was well-tolerated and induced robust antibody and cellular responses, notably against both homologous and drifted A/H3N2 viruses in Phase 1, 2, and 3 trials. We also developed a full-length SARS-CoV-2 spike PROTEIN protein vaccine stable in the prefusion conformation (NVX-CoV2373) using the same platform technology. In phase 3 clinical trials, NVX-CoV2373 is highly immunogenic and protective against the prototype strain and B.1.1.7 variant. Here we describe the immunogenicity and efficacy of a combination quadrivalent seasonal flu and COVID-19 MESHD vaccine (qNIV/CoV2373). In ferret and hamster models, qNIV/CoV2373 vaccine produces high titer influenza hemagglutination inhibiting (HAI) and neutralizing antibodies against influenza A and B strains. The combination vaccine also elicited antibodies that block SARS-CoV-2 spike PROTEIN protein binding to the human angiotensin converting enzyme-2 HGNC ( hACE2 HGNC) receptor. Significantly, hamsters immunized with qNIV/CoV2373 vaccine and challenged with SARS-CoV-2 were protected against weight loss MESHD and were free of replicating SARS-CoV-2 in the upper and lower respiratory tract with no evidence of viral pneumonia MESHD. This study supports evaluation of qNIV/CoV2373 combination vaccine as a preventive measure for seasonal influenza and CoVID-19 MESHD.

    SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern induce lethal disease in K18- hACE2 HGNC transgenic mice despite convalescent plasma therapy

    Authors: Alexander M Horspool; Chengjin Ye; Ting Y. Wong; Brynnan P. Russ; Katherine S. Lee; Michael T. Winters; Justin R. Bevere; Theodore Kieffer; Ivan Martinez; Julien Sourimant; Alexander L. Greninger; Richard K. Plemper; James Denvir; Holly A. Cyphert; Jordi B Torrelles; Luis Martinez-Sobrido; Fredrick Heath Damron

    doi:10.1101/2021.05.05.442784 Date: 2021-05-05 Source: bioRxiv

    SARS-CoV-2 variants of concern (VoCs) are impacting responses to the COVID-19 pandemic MESHD. Here we present a comparison of the SARS-CoV-2 USA-WA1/2020 (WA-1) strain with B.1.1.7 and B.1.351 VoCs and identify significant differences in viral propagation in vitro and pathogenicity in vivo using K18- hACE2 HGNC transgenic mice. Passive immunization with plasma from an early pandemic SARS-CoV-2 patient resulted in significant differences in the outcome of VoC-infected MESHD mice. WA-1-infected mice were protected by plasma, B.1.1.7-infected mice were partially protected, and B.1.351-infected mice were not protected. Serological correlates of disease were different between VoC-infected MESHD mice, with B.1.351 triggering significantly altered cytokine profiles than other strains. In this study, we defined infectivity and immune responses triggered by VoCs and observed that early 2020 SARS-CoV-2 human immune plasma was insufficient to protect against challenge with B.1.1.7 and B.1.351 in the mouse model.

    Sex-biased response to and brain cell infection MESHD by SARS-CoV-2 in a highly susceptible human ACE2 HGNC transgenic model

    Authors: Ching-Yen Tsai; Yu-Chi Chou; Chiung-Ya Chen; Jia-Tsrong Jan; Mei-Ling Chang; Lu-A Lu; Pau-Yi Huang; Tsan-Ting Hsu; Yi-Ping Hsueh

    doi:10.1101/2021.05.04.441029 Date: 2021-05-04 Source: bioRxiv

    The COVID-19 pandemic MESHD is caused by SARS-CoV-2 infection MESHD. Human angiotensin-converting enzyme II ( hACE2 HGNC) has been identified as the receptor enabling SARS-CoV-2 host entry. To establish a mouse model for COVID-19 MESHD, we generated transgenic mouse lines using the (HS4)2-pCAG- hACE2 HGNC-HA-(HS4)2 transgene cassette, which expresses HA-tagged hACE2 HGNC under control of the CAG promoter and is flanked by HS4 insulators. Expression levels of the hACE2 HGNC transgene are respectively higher in lung, brain and kidney of our CAG- hACE2 HGNC transgenic mice and relatively lower in duodenum, heart and liver. The CAG- hACE2 HGNC mice are highly susceptibility to SARS-CoV-2 infection MESHD, with 100 PFU of SARS-CoV-2 being sufficient to induce 87.5% mortality at 9 days post-infection and resulting in a sole (female) survivor. Mortality was 100% at the higher titer of 1000 PFU. At lower viral titers, we also found that female mice exposed to SARS-CoV-2 infection MESHD suffered much less weight loss MESHD than male mice, implying sex-biased responses to SARS-CoV-2 infection MESHD. We subjected neuronal cultures to SARS-CoV-2 pseudovirus infection MESHD to ascertain the susceptibilities of neurons and astrocytes. Moreover, we observed that expression of SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein alters the synaptic responses of cultured neurons. Our transgenic mice may serve as a model for severe COVID-19 MESHD and sex-biased responses to SARS-CoV-2 infection MESHD, aiding in the development of vaccines and therapeutic treatments for this disease.

    A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice

    Authors: Tirosh Shapira; I. Abrrey Monreal; Sébastien P Dion; Mason Jager; Antoine Désilets; Andrea D Olmstead; Thierry Vandal; David W Buchholz; Brian Imbiakha; Guang Gao; Aaleigha Chin; William D Rees; Theodore Steiner; Ivan Robert Nabi; Eric Marsault; Julie Sahler; Avery August; Gerlinde Van de Walle; Gary R Whittaker; Pierre-Luc Boudreault; Hector C Aguilar; Richard Leduc; François Jean

    doi:10.1101/2021.05.03.442520 Date: 2021-05-04 Source: bioRxiv

    The COVID-19 pandemic MESHD caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced against emerging variants of concern (VOCs). Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs. Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs), such as TMPRSS2 HGNC, whose essential role in the virus lifecycle is responsible for the cleavage and priming of the viral spike protein PROTEIN. Here, we identify and characterize a small-molecule compound, N-0385, as the most potent inhibitor of TMPRSS2 HGNC reported to date. N-0385 exhibited low nanomolar potency and a selectivity index of > 1 million at inhibiting SARS-CoV-2 infection MESHD in human lung cells and in donor-derived colonoids. Importantly, N-0385 acted as a broad-spectrum coronavirus inhibitor of two SARS-CoV-2 VOCs, B.1.1.7 and B.1.351. Strikingly, single daily intranasal administration of N-0385 early in infection significantly improved weight loss MESHD and clinical outcomes, and yielded 100% survival in the severe K18-human ACE2 HGNC transgenic mouse model of SARS-CoV-2 disease MESHD. This demonstrates that TTSP-mediated proteolytic maturation of spike is critical for SARS-CoV-2 infection MESHD in vivo and suggests that N-0385 provides a novel effective early treatment option against COVID-19 MESHD and emerging SARS-CoV-2 VOCs MESHD.

    SARS-CoV-2 spike PROTEIN protein induces brain pericyte immunoreactivity in absence of productive viral infection

    Authors: Rayan Khaddaj-Mallat; Natija Aldib; Anne-Sophie Paquette; Aymeric Ferreira; Sarah Lecordier; Maxime Bernard; Armen Saghatelyan; Ayman ElAli

    doi:10.1101/2021.04.30.442194 Date: 2021-05-03 Source: bioRxiv

    COVID-19 MESHD is a respiratory disease MESHD caused by severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2). COVID-19 MESHD pathogenesis causes vascular-mediated neurological disorders MESHD via still elusive mechanisms. SARS-CoV-2 infects host MESHD cells by binding to angiotensin-converting enzyme 2 HGNC (ACE2), a transmembrane receptor that recognizes the viral spike (S) protein PROTEIN. Brain pericytes were recently shown to express ACE2 at the neurovascular interface, outlining their possible implication in microvasculature injury MESHD in COVID-19 MESHD. Yet, pericyte responses to SARS-CoV-2 is still to be fully elucidated. Using cell-based assays, we report that ACE2 HGNC expression in human brain vascular pericytes is highly dynamic and is increased upon S protein PROTEIN stimulation. Pericytes exposed to S protein PROTEIN underwent profound phenotypic changes translated by increased expression of contractile and myofibrogenic proteins, namely -smooth muscle actin (- SMA HGNC), fibronectin HGNC, collagen I, and neurogenic locus notch homolog protein-3 HGNC ( NOTCH3 HGNC). These changes were associated to an altered intracellular calcium (Ca2+) dynamic. Furthermore, S protein PROTEIN induced lipid peroxidation, oxidative and nitrosative stress in pericytes as well as triggered an immune reaction translated by activation of nuclear factor-kappa-B ( NF-{kappa}B HGNC) signalling pathway, which was potentiated by hypoxia MESHD, a condition associated to vascular comorbidities, which exacerbate COVID-19 MESHD pathogenesis. S protein PROTEIN exposure combined to hypoxia MESHD enhanced the production of pro-inflammatory cytokines involved in immune cell activation and trafficking, namely interleukin-8 HGNC ( IL-8 HGNC), IL-18 HGNC, macrophage migration inhibitory factor HGNC ( MIF HGNC), and stromal cell-derived factor-1 HGNC ( SDF-1 HGNC). Finally, we found that S protein PROTEIN could reach the mouse brain via the intranasal route and that reactive ACE2-expressing pericytes are recruited to the damaged tissue undergoing fibrotic scarring in a mouse model of cerebral multifocal micro-occlusions, a main reported vascular-mediated neurological condition associated to COVID-19 MESHD. Our data demonstrate that the released S protein PROTEIN is sufficient to mediate pericyte immunoreactivity, which may contribute to microvasculature injury MESHD in absence of a productive viral infection MESHD. Our study provides a better understanding for the possible mechanisms underlying cerebrovascular disorders MESHD in COVID-19 MESHD, paving the way to develop new therapeutic interventions.

    In silico and in vitro Demonstration of Homoharrintonine Antagonism of RBD- ACE2 HGNC Binding and its Anti-inflammatory and anti-thrombogenic Properties in a 3D human vascular lung model

    Authors: Shalini Saxena; Kranti Meher; Madhuri Rotella; Subhramanyam Vangala; Satish Chandran; Nikhil Malhotra; Ratnakar Palakodeti; Sreedhara Voleti; Uday Saxena

    doi:10.1101/2021.05.02.442384 Date: 2021-05-03 Source: bioRxiv

    Since 2019 the world has seen severe onslaught of SARS-CoV-2 viral pandemic. There is an urgent need for drugs that can be used to either prevent or treat the potentially fatal disease COVD-19. To this end, we screened FDA approved antiviral drugs which could be repurposed for COVID-19 MESHD through molecular docking approach in the various active sites of receptor binding domain (RBD). The RBD domain of SARS-CoV-2 spike PROTEIN protein is a promising drug target due to its pivotal role in viral-host attachment. Specifically, we focussed on identifying antiviral drugs which could a) block the entry of virus into host cells, b) demonstrate anti-inflammatory and/or anti-thrombogenic properties. Drugs which poses both properties could be useful for prevention and treatment of the disease. While we prioritized a few antiviral drugs based on molecular docking, corroboration with in vitro studies including a new 3D human vascular lung model strongly supported the potential of Homoharringtonine, a drug approved for chronic myeloid leukaemia MESHD to be repurposed for COVID-19 MESHD. This natural product drug not only antagonized the biding of SARS-CoV-2 spike PROTEIN protein RBD binding to human angiotensin receptor 2 ( ACE-2 HGNC) protein but also demonstrated for the first time anti-thrombogenic and anti-leukocyte adhesive properties in a human cell model system. Overall, this work provides an important lead for development of rapid treatment of COVID-19 MESHD and also establishes a screening paradigm using molecular modelling and 3D human vascular lung model of disease to identify drugs with multiple desirable properties for prevention and treatment of COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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