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SARS-CoV-2 proteins

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    Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein

    Authors: Sarah Lapidus; Feimei Liu; Arnau Casanovas-Massana; Yile Dai; John D. Huck; Carolina Lucas; Jon Klein; Renata B. Filler; Madison S. Strine; Mouhamad Sy; Awa B. Deme; Aida S. Badiane; Baba Dieye; Ibrahima Mbaye Ndiaye; Younous Diedhiou; Amadou Moctar Mbaye; Cheikh Tidiane Diagne; Inés Vigan-Womas; Alassane Mbengue; Bacary D. Sadio; Moussa M. Diagne; Adam J. Moore; Khadidiatou Mangou; Fatoumata Diallo; Seynabou D. Sene; Mariama N. Pouye; Rokhaya Faye; Babacar Diouf; Nivison Nery Jr; Federico Costa; Mitermayer Reis; M. Catherine Muenker; Daniel Z. Hodson; Yannick Mbarga; Ben Z. Katz; Jason R. Andrews; Melissa Campbell; Ariktha Srivathsan; Kathy Kamath; Elisabeth Baum-Jones; Ousmane Faye; Amadou Alpha Sall; Juan Carlos Quintero Vélez; Michael Cappello; Michael Wilson; Choukri Ben-Mamoun; Fabrice A. Somé; Roch K. Dabiré; Carole Else Eboumbou Moukoko; Jean Bosco Ouédraogo; Yap Boum II; John Shon; Daouda Ndiaye; Adam Wisnewski; Sunil Parikh; Akiko Iwasaki; Craig B. Wilen; Albert I. Ko; Aaron M. Ring; Amy K. Bei

    doi:10.1101/2021.05.10.21256855 Date: 2021-05-12 Source: medRxiv

    Individuals with acute malaria infection MESHD generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein PROTEIN and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein PROTEIN-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria MESHD-endemic countries.

    Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms

    Authors: Ana C Puhl; Ethan J Fritch; Thomas R Lane; Longping V Tse; Boyd Yount; Carol Q Sacramento; Tatyana A Tavella; Fabio T. M. Costa; Stuart Weston; James Logue; Matthew Frieman; Lakshmanane Premkumar; Kenneth H Pearce; Brett L Hurst; Carolina H Andrade; James A Levi; Nicole J Johnson; Samantha C Kisthardt; Frank Scholle; Thiago ML Souza; Nathanial J Moorman; Ralph S. Baric; Peter Madrid; Sean Ekins; Monica Pinto; Daniela Cardemil; Marcelo Navarrete; Soledad Reyes; Victoria Espinoza; Nicolas Yanez; Christian Caglevic

    doi:10.1101/2020.12.01.407361 Date: 2020-12-02 Source: bioRxiv

    SARS-CoV-2 is a newly identified virus that has resulted in over 1.3 M deaths globally and over 59 M cases globally to date. Small molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shown in vitro activity against Ebola virus and demonstrated activity against SARS-CoV-2 in vivo. Most notably the RNA polymerase targeting remdesivir demonstrated activity in vitro and efficacy in the early stage of the disease in humans. Testing other small molecule drugs that are active against Ebola virus would seem a reasonable strategy to evaluate their potential for SARS-CoV-2. We have previously repurposed pyronaridine, tilorone and quinacrine (from malaria MESHD, influenza, and antiprotozoal uses, respectively) as inhibitors of Ebola and Marburg virus in vitro in HeLa cells and of mouse adapted Ebola virus in mouse in vivo. We have now tested these three drugs in various cell lines (VeroE6, Vero76, Caco-2, Calu-3, A549-ACE2, HUH-7 and monocytes) infected with SARS-CoV-2 as well as other viruses (including MHV and HCoV 229E). The compilation of these results indicated considerable variability in antiviral activity observed across cell lines. We found that tilorone and pyronaridine inhibited the virus replication in A549-ACE2 cells with IC50 values of 180 nM and IC50 198 nM, respectively. We have also tested them in a pseudovirus assay and used microscale thermophoresis to test the binding of these molecules to the spike protein PROTEIN. They bind to spike RBD protein with Kd values of 339 nM and 647 nM, respectively. Human Cmax for pyronaridine and quinacrine is greater than the IC50 hence justifying in vivo evaluation. We also provide novel insights into their mechanism which is likely lysosomotropic.

    Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2

    Authors: Tianling Ou; Huihui Mou; Lizhou Zhang; Amrita Ojha; Hyeryun Choe; Michael Farzan

    doi:10.1101/2020.07.22.216150 Date: 2020-07-22 Source: bioRxiv

    Hydroxychloroquine, used to treat malaria MESHD and some autoimmune disorders MESHD, potently inhibits viral infection of SARS coronavirus (SARS-CoV-1) and SARS-CoV-2 MESHD in cell-culture studies. However, human clinical trials of hydroxychloroquine failed to establish its usefulness as treatment for COVID-19 MESHD. This compound is known to interfere with endosomal acidification necessary to the proteolytic activity of cathepsins. Following receptor binding and endocytosis, cathepsin L HGNC can cleave the SARS-CoV-1 and SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN ( S) proteins PROTEIN, thereby activating membrane fusion for cell entry. The plasma membrane-associated protease TMPRSS2 HGNC can similarly cleave these S proteins PROTEIN and activate viral entry at the cell surface. Here we show that the SARS-CoV-2 entry process is more dependent than that of SARS-CoV-1 on TMPRSS2 HGNC expression. This difference can be reversed when the furin-cleavage site of the SARS-CoV-2 S protein PROTEIN is ablated. We also show that hydroxychloroquine efficiently blocks viral entry mediated by cathepsin L HGNC, but not by TMPRSS2 HGNC, and that a combination of hydroxychloroquine and a clinically-tested TMPRSS2 HGNC inhibitor prevents SARS-CoV-2 infection MESHD more potently than either drug alone. These studies identify functional differences between SARS-CoV-1 and -2 entry processes, and provide a mechanistic explanation for the limited in vivo utility of hydroxychloroquine as a treatment for COVID-19 MESHD. Author SummaryThe novel pathogenic coronavirus SARS-CoV-2 causes COVID-19 MESHD and remains a threat to global public health. Chloroquine and hydroxychloroquine have been shown to prevent viral infection in cell-culture systems, but human clinical trials did not observe a significant improvement in COVID-19 MESHD patients treated with these compounds. Here we show that hydroxychloroquine interferes with only one of two somewhat redundant pathways by which the SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN is activated to mediate infection. The first pathway is dependent on the endosomal protease cathepsin L HGNC and sensitive to hydroxychloroquine, whereas the second pathway is dependent on TMPRSS2 HGNC, which is unaffected by this compound. We further show that SARS-CoV-2 is more reliant than SARS coronavirus (SARS-CoV-1) on the TMPRSS2 HGNC pathway, and that this difference is due to a furin cleavage site present in the SARS-CoV-2 S protein PROTEIN. Finally, we show that combinations of hydroxychloroquine and a clinically tested TMPRSS2 HGNC inhibitor work together to effectively inhibit SARS-CoV-2 entry. Thus TMPRSS2 HGNC expression on physiologically relevant SARS-CoV-2 target cells may bypass the antiviral activities of hydroxychloroquine, and explain its lack of in vivo efficacy.

    The emergence of SARS-CoV-2 by an unusual genome reconstitution

    Authors: Seong-Tshool Hong; Md. Mehedi Hassan; Shirina Sharmin; Jinny Hong; Hoi-Seon Lee; Hyeon Jin Kim

    doi:10.21203/rs.3.rs-33201/v1 Date: 2020-06-03 Source: ResearchSquare

    SARS-CoV-2 has been spreading remarkedly fast around the world since its emergence while the origin of the virus remains ambiguous. Here, we constructed all of the original prototype genome sequences of SARS-CoV-2 by selecting the common nucleotide among the different virus strains with species. Phylogenetic analysis on the prototype sequences showed that SARS-CoV-2 was a direct descendant of Bat-CoV and was closely related to Pan-CoV, Bat-SL-CoV, and SARS-CoV MESHD. The pairwise comparison of SARS-CoV-2 with Bat-CoV showed an unusual replacement of the motif consisting of 7 amino acids within the spike protein PROTEIN of SARS-CoV-2. Database searches showed that the motif originated from a surface protein of Plasmodium malariae MESHD, suggesting that the SARS-CoV-2 was emerged after acquiring the motif of the malaria MESHD surface protein.

    ACE 2 HGNC Coding Variants: A Potential X-linked Risk Factor for COVID-19 MESHD Disease

    Authors: William T Gibson; Daniel M Evans

    doi:10.1101/2020.04.05.026633 Date: 2020-04-14 Source: bioRxiv

    Viral genetic variants are widely known to influence disease progression among infected humans. Given the recent and rapid emergence of pandemic SARS-CoV-2 infection MESHD, the cause of COVID-19 MESHD disease, viral protein variants have attracted research interest. However, little has yet been written about genetic risk factors among human hosts. Human genetic variation has proven to affect disease progression and outcome for important diseases such as HIV infection MESHD and malaria infestation MESHD. The fact that the human ACE2 HGNC protein is encoded on the X chromosome means that males who carry rare ACE2 HGNC coding variants will express those variants in all ACE2 HGNC-expressing cells, whereas females will typically express those variants in a mosaic distribution determined by early X-inactivation events. This sex-based difference in ACE2 HGNC expression has unique implications for epidemiological studies designed to assess host genetic factors influencing progression from asymptomatic SARS-coV-2 infection MESHD to COVID-19 MESHD. Here we present theoretical modelling of rare ACE2 HGNC coding variants documented to occur naturally in several human superpopulations and subpopulations, and show that rare variants predicted to affect the binding of ACE2 HGNC to the SARS-CoV-2 spike PROTEIN protein exist in people. Though the rs4646116 (p.Lys26Arg) allele is found in 1 in 70 Ashkenazi Jewish males, and in 1 in 172 non-Finnish European males, this allele is found at higher frequencies in females. Furthermore, the class of missense ACE2 HGNC alleles predicted to affect SARS-CoV-2 binding are found in aggregate among 1.43% and 2.16% of Ashkenazi males and females, respectively, as well as in 0.58% and 1.24% of European males and females outside of Finland. These alleles are rarer in other population groups, and almost absent from East Asians genotyped to date. Though we are aware that full genome-wide and exome-wide sequencing studies may ultimately be required to assess human genetic susceptibility to SARS-CoV-2 fully, we argue on the basis of strong prior probabilities that genotyping of this class of alleles is justified in cases of atypical SARS-CoV-2 diseases, such as asymptomatic super-spreaders (if any are identified), and in neonatal/paediatric-onset COVID-19 MESHD disease. Even relatively rare susceptibility factors (1% or fewer carriers) may become quantitatively important in the context of hundreds of thousands of infections. A small number of asymptomatic carriers, or a small number of super-spreaders, or a small segment of the population that is disproportionately likely to require intensive care, can magnify the medical, social and economic impacts of a pandemic of this size. The speed of the pandemic and the large number of affected cases worldwide justify efforts to identify all possible risk factors for adverse outcomes, including efforts to identify genetic susceptibility factors in human hosts.

    Bioinformatics approaches to understand the interactions between the SARS corona Virus (SARS-CoV19) with stranded drugs of anti-retro viral treatment, Influenza and Malaria.

    Authors: Santhoshi Rani Nanchari; Shyam perugu

    doi:10.21203/rs.3.rs-20010/v1 Date: 2020-03-28 Source: ResearchSquare

    Background: Severe acute respiratory syndrome MESHD (SARS) is highly contagious disease caused by virus COVID19 MESHD. The first case is reported in Wuhan, China, with rapid spreading all over the world and the rate of mortality is also high. SARS-CoV MESHD and another human coronavirus, HCoV-NL63 has large spike protein (S PROTEIN) on the virion surface mediates both cell attachment and membrane fusion with receptor sites present on host cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2). Methodology: In the present study, molecular docking studies have been carried out to assess the interaction between the novel corona virus protein COVID19 MESHD with stranded drugs used for influenza, anti-retro viral therapy and malaria MESHD drugs by using Accelerys discovery studio 2.5, followed by analysis of data. The present study will help to design the drugs against the corona virus and understand the mode of treatment for SARS. Results: All the four-protein receptor of COVID 19 proteins at particular amino acid position binds to the NH and H atom of anti-retro viral therapy drugs (Atazanavir, Doravirine, Emitricitabine, Entravirine, Raltegravir, Tenofavir Disproxil, and Zidovudin) and anti- malaria MESHD drug (Hydroxy chloroquine) with less hydrogen bond distance with maximum docking scores which indicates that these compounds can acts against the COVID19 MESHD virus. Gene mania MESHD network help to design the novel drugs and diagnosis. Conclusions: This is first report to show the molecular docking interaction between the COVID19 MESHD protein with stranded drugs of anti -viral treatment. anti-viral drugs Atazanavir, Doravirine, Emitricitabine, Entravirine, Raltegravir, Tenofavir Disproxil, and Zidovudin and malaria drug Hydroxy MESHD chloroquine has more strong binding with COVID19 MESHD protein receptors.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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