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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2)

ORF8 (2)

NSP5 (1)

NSP6 (1)

ORF3a (1)


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SARS-CoV-2 Proteins
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    Different mutations in SARS-CoV-2 associate with severe and mild outcome

    Authors: Adam Nagy; Sandor Pongor; Balazs Gyorffy

    doi:10.1101/2020.10.16.20213710 Date: 2020-10-20 Source: medRxiv

    Introduction. Genomic alterations in a viral genome can lead to either better or worse outcome and identifying these mutations is of utmost importance. Here, we correlated protein-level mutations in the SARS-CoV-2 virus to clinical outcome. Methods. Mutations in viral sequences from the GISAID virus repository were evaluated by using hCoV-19/Wuhan/WIV04/2019 as the reference. Patient outcomes were classified as mild disease, hospitalization and severe disease ( death MESHD or documented treatment in an intensive-care unit). Chi-square test was applied to examine the association between each mutation and patient outcome. False discovery rate was computed to correct for multiple hypothesis testing and results passing a FDR cutoff of 5% were accepted as significant. Results. Mutations were mapped to amino acid changes for 2,120 non-silent mutations. Mutations correlated to mild outcome were located in the ORF8 PROTEIN, NSP6 PROTEIN, ORF3a PROTEIN, NSP4 PROTEIN NSP4 HGNC, and in the nucleocapsid phosphoprotein N. Mutations associated with inferior outcome were located in the surface ( S) glycoprotein PROTEIN, in the RNA dependent RNA polymerase PROTEIN, in the 3'-to5' exonuclease, in ORF3a PROTEIN, NSP2 HGNC NSP2 PROTEIN and N. Mutations leading to severe outcome with low prevalence were found in the surface ( S) glycoprotein PROTEIN and in NSP7 PROTEIN. Five out of 17 of the most significant mutations mapped onto a 10 amino acid long phosphorylated stretch of N indicating that in spite of obvious sampling restrictions the approach can find functionally relevant sites in the viral genome. Conclusions. We demonstrate that mutations in the viral genes may have a direct correlation to clinical outcome. Our results help to quickly identify SARS-CoV-2 infections MESHD harboring mutations related to severe outcome.

    Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function

    Authors: Alejandro Berrio; Valerie Gartner; Gregory A. Wray; Yeo-Eun Cha; Sim Namkoong; Jin I Lee; Junsoo Park; Chittibabu Guda; Mara J Broadhurst; St Patrick Reid; Kenneth W Bayles; Gloria E.O Borgstahl; Prakash Radhakrishnan; Keivan Zandi; Sijia Tao; Tristan R Horton; Elizabeth N Beagle; Ernestine A Mahar; Michelle YH Lee; Joyce Cohen; Sherrie Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Olivia M Delmas; Shelly Wang; Kimberly A Cooney; Michael N Sayegh; Lanfang Wang; Daniela Weiskopf; Peter D Filev; Jesse Waggoner; Anne Piantadosi; Sudhir P Kasturi; Hilmi Al-Shakhshir; Susan P Ribeiro; Rafick P Sekaly; Rebecca D Levit; Jacob D Estes; Thomas H Vanderford; Raymond F Schinazi; Steven E Bosinger; Mirko Paiardini

    doi:10.1101/2020.09.16.300038 Date: 2020-09-16 Source: bioRxiv

    Background: The emergence of a novel coronavirus (SARS-CoV-2) associated with severe acute respiratory disease MESHD ( COVID-19 MESHD) has prompted efforts to understand the genetic basis for its unique characteristics and its jump from non-primate hosts to humans. Tests for positive selection can identify apparently nonrandom patterns of mutation accumulation within genomes, highlighting regions where molecular function may have changed during the origin of a species. Several recent studies of the SARS-CoV-2 genome have identified signals of conservation and positive selection within the gene encoding Spike protein PROTEIN based on the ratio of synonymous to nonsynonymous substitution. Such tests cannot, however, detect changes in the function of RNA molecules. Methods: Here we apply a test for branch-specific oversubstitution of mutations within narrow windows of the genome without reference to the genetic code. Results: We recapitulate the finding that the gene encoding Spike protein PROTEIN has been a target of both purifying and positive selection. In addition, we find other likely targets of positive selection within the genome of SARS-CoV-2, specifically within the genes encoding Nsp4 HGNC and Nsp16. Homology-directed modeling indicates no change in either Nsp4 HGNC or Nsp16 protein structure relative to the most recent common ancestor. Thermodynamic modeling of RNA stability and structure, however, indicates that RNA secondary structure within both genes in the SARS-CoV-2 genome differs from those of RaTG13, the reconstructed common ancestor, and Pan-CoV-GD (Guangdong). These SARS-CoV-2-specific mutations may affect molecular processes mediated by the positive or negative RNA molecules, including transcription, translation, RNA stability, and evasion of the host innate immune system. Our results highlight the importance of considering mutations in viral genomes not only from the perspective of their impact on protein structure, but also how they may impact other molecular processes critical to the viral life cycle.

    The global population of SARS-CoV-2 is composed of six major subtypes

    Authors: Ivair Jose Morais Junior; Richard Costa Polveiro; Gabriel Medeiros Souza; Daniel Inserra Bortolin; Flavio Tetsuo Sassaki; Alison Talis Martins Lima

    doi:10.1101/2020.04.14.040782 Date: 2020-04-15 Source: bioRxiv

    The World Health Organization characterized the COVID-19 MESHD as a pandemic in March 2020, the second pandemic of the 21st century. Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is a positive-stranded RNA betacoronavirus of the family Coronaviridae. Expanding virus populations, as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for a robust clustering. Here, we proposed the subdivision of the global SARS-CoV-2 population into sixteen well-defined subtypes by focusing on the widely shared polymorphisms in nonstructural ( nsp3 HGNC, nsp4 HGNC, nsp6, nsp12, nsp13 and nsp14) cistrons, structural (spike and nucleocapsid) and accessory ( ORF8 PROTEIN) genes. Six virus subtypes were predominant in the population, but all sixteen showed amino acid replacements which might have phenotypic implications. We hypothesize that the virus subtypes detected in this study are records of the early stages of the SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world, a typical founder effect. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing the candidate vaccines or drugs.

    In Silico Guided Drug Repurposing to Combat SARS-CoV-2 by Targeting Mpro PROTEIN, the Key Virus Specific Protease

    Authors: Ruchi Rani; Ankur Singh; Akshay Pareek; Shailly Tomar

    doi:10.26434/chemrxiv.12030345.v1 Date: 2020-03-26 Source: ChemRxiv

    The reemergence of SARS-CoV MESHD named, as SARS-CoV-2 has been highly infectious and able to infect a large population around the globe. The World Health Organization (WHO) has declared this SARS-CoV-2 associated Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) as pandemic. SARS-CoV-2 genome is translated into polyproteins and has been processed by its protease enzymes. 3CLprotease is named as main protease PROTEIN ( Mpro PROTEIN) enzyme which cleaves nsp4 HGNC-nsp16. This crucial role of Mpro PROTEIN makes this enzyme a prime and promising antiviral target. The drug repurposing is a fast alternative method than the discovery of novel antiviral molecules. We have used high-throughput virtual screening approach to examine FDA approved LOPAC1280 library against Mpro PROTEIN. Primary screening have identified few potential drug molecule for the target among which 10 molecules were studied further. Molecular docking of selected molecules was done to detailed study about their binding energy and binding modes. Positively, Etoposide, BMS_195614, KT185, Idarubicin and WIN_62577 were found interacting with substrate binding pocket of Mpro PROTEIN with higher binding energy. These molecules are being advanced by our group for in vitro and in vivo testing to study the efficacy of identified drugs. As per our understanding, these molecules have the potential to efficiently interrupt the viral life cycle and may reduce or eliminate the expeditious outspreading of SARS-CoV-2.

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