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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF7a (38)

ORF8 (15)

ProteinS (13)

ORF3a (10)

ORF6 (10)


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SARS-CoV-2 Proteins
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    Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses

    Authors: Hong Zhou; Jingkai Ji; Xing Chen; Yuhai Bi; Juan Li; Tao Hu; Hao Song; Yanhua Chen; Mingxue Cui; Yanyan Zhang; Alice C. Hughes; Edward C. Holmes; Weifeng Shi

    doi:10.1101/2021.03.08.434390 Date: 2021-03-08 Source: bioRxiv

    Although a variety of SARS-CoV-2 related coronaviruses have been identified, the evolutionary origins of this virus remain elusive. We describe a meta-transcriptomic study of 411 samples collected from 23 bat species in a small (~1100 hectare) region in Yunnan province, China, from May 2019 to November 2020. We identified coronavirus contigs in 40 of 100 sequencing libraries, including seven representing SARS-CoV-2-like contigs. From these data we obtained 24 full-length coronavirus genomes, including four novel SARS-CoV-2 related and three SARS-CoV MESHD related genomes. Of these viruses, RpYN06 exhibited 94.5% sequence identity to SARS-CoV-2 across the whole genome and was the closest relative of SARS-CoV-2 in the ORF1ab PROTEIN, ORF7a PROTEIN, ORF8 PROTEIN, N, and ORF10 PROTEIN genes. The other three SARS-CoV-2 related coronaviruses were nearly identical in sequence and clustered closely with a virus previously identified in pangolins from Guangxi, China, although with a genetically distinct spike gene sequence. We also identified 17 alphacoronavirus genomes, including those closely related to swine acute diarrhea syndrome MESHD virus and porcine epidemic diarrhea virus MESHD. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species in Southeast Asia and southern China, with the largest contiguous hotspots extending from South Lao HGNC and Vietnam to southern China. Our study highlights both the remarkable diversity of bat viruses at the local scale and that relatives of SARS-CoV-2 and SARS-CoV circulate in wildlife species in a broad geographic region of Southeast Asia and southern China. These data will help guide surveillance efforts to determine the origins of SARS-CoV-2 and other pathogenic coronaviruses.

    SARS-CoV-2 genomic surveillance identifies naturally occurring truncations of ORF7a PROTEIN that limit immune suppression

    Authors: Artem A Nemudryi; Anna A Nemudraia; Tanner Wiegand; Joseph Nichols; Deann T Snyder; Jodi F Hedges; Calvin Cicha; Helen H Lee; Karl K Vanderwood; Diane Bimczok; Mark A Jutila; Blake A Wiedenheft

    doi:10.1101/2021.02.22.21252253 Date: 2021-02-24 Source: medRxiv

    Over 200,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a PROTEIN. We have isolated one of these mutant viruses from a patient sample and used viral chal-lenge experiments to demonstrate that {Delta}115 mutation results in a growth defect MESHD. ORF7a PROTEIN has been implicated in immune modulation, and we show that the C-terminal truncation results in distinct changes in interferon stimulated gene expression. Collectively, this work indicates that ORF7a PROTEIN mutations occur frequently and that these changes affect viral mechanisms responsible for suppressing the immune response. HighlightsO_LIORF7a mutations are found in SARS-CoV-2 genomes isolated from around the globe. C_LIO_LIORF7a mutation results in a replication defect. C_LIO_LIAn ORF7a PROTEIN mutation limits viral suppression of the interferon response. C_LI

    Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells

    Authors: Adam Pickard; Ben C Calverley; Joan Chang; Richa Garva; Yinhui Lu; Karl E Kadler

    doi:10.1101/2021.01.31.428851 Date: 2021-02-01 Source: bioRxiv

    Background: The SARS-CoV-2 virus that was first identified in Wuhan, China has caused the death of over 2 million people worldwide during the COVID-19 pandemic MESHD. Whilst effective vaccines have been developed and vaccination schedules are being rolled out, the identification of safe and inexpensive drugs to slow the replication of SARS-CoV-2 could help thousands of people worldwide whilst awaiting vaccination. Methods: Using SARS-CoV-2 tagged with nano-luciferase (SARS-CoV-2-{Delta} Orf7a PROTEIN-NLuc) we screened a variety of cells under optimised cell culture conditions for their ability to be infected by, and support the replication of, SARS-CoV-2. Electron microscopy was used to demonstrate generation of infectious virus particles. We assessed a library of 1971 FDA-approved drugs for their ability to inhibit or enhance viral replication in Vero (simian kidney cells) but also in the human hepatocyte cell, HUH7 HGNC. Initial hits were further tested to identify compounds that could suppress viral replication, post-viral infection. Dose response curves were obtained for a shortlist of 9 compounds of interest ( COI HGNC). Findings: Our SARS-CoV-2-{Delta} Orf7a PROTEIN-NLuc virus was as effective as wild-type SARS-CoV-2 in inducing CPE and replicating in Vero cells. Conventional electron microscopy showed the NLuc-tagged virus to be structurally indistinguishable from the wild-type virus, and both could be identified within the endosomal system of infected cells. SARS-CoV-2-{Delta} Orf7a PROTEIN-NLuc was used in experiments to robustly quantitate virus infection MESHD and replication. A wide variety of human cells including lung fibroblasts and epithelial cells were susceptible to infection but were not effective in supporting SARS-CoV-2-{Delta} Orf7a PROTEIN-NLuc replication. In contrast, human kidney epithelial cells and human hepatic cells were particularly susceptible and supported SARS-CoV-2-replication, which is in-line with reported proteinuria MESHD and liver damage MESHD in patients with COVID-19 MESHD. Our screening of FDA approved compounds identified 35 COI HGNC that inhibited virus infection MESHD and replication in either Vero or human cell lines. Nine of these also inhibited SARS-CoV-2 replication when treatment commenced after virus infection MESHD. Therapeutics approved for treatment of cancer MESHD, malaria MESHD, hypertension MESHD and viral infection MESHD were identified with atovaquone, manidipine, vitamin D3 and ebastine being well tolerated with minimal side effects. Only two COI HGNC were consistently found to enhance SARS-CoV-2 replication, aliskiren and lithocholic acid. Interpretation: Re-purposing of safe, well-tolerated FDA-approved drugs that inhibit SARS-CoV-2 replication is an attractive strategy to reduce the risk of COVID-19 MESHD infection prior to receiving an effective vaccine. The COI HGNC identified here hold potential to contain COVID-19 MESHD whilst wide-scale vaccination proceeds. The identification of FDA-approved drugs that enhance SARS-CoV-2 replication in human cells suggests that entry routes into cells can be made more accessible to the virus by certain medications. The information provided in this research paper is for information only and is not meant to be a substitute for advice provided by a doctor or other qualified health care professional.

    Unravelling Vitamins as Wonder Molecules for Covid-19 MESHD Management via Structure-based Virtual Screening

    Authors: Medha Pandya; Sejal Shah; Dhanalakshmi Menamadathil; Ayushman Gadnayak; Tanzil Juneja; Amisha Patel; Kajari Das; Jayashankar Das

    doi:10.21203/rs.3.rs-144177/v1 Date: 2021-01-09 Source: ResearchSquare

    The emergence situation of coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic has realised the global scientific communities to develop strategies for immediate priorities and long-term approaches for utilization of existing knowledge and resources which can be diverted to pandemic preparedness planning. Lack of proper vaccine candidate and therapeutic management has accelerated the researchers to repurpose the existing drugs with known preclinical and toxicity MESHD profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. We focused to justify even exploration of supplements, nutrients and vitamins to dampen the disease burden of the current pandemic may play a crucial role for its management. We have explored structure based virtual screening of 15 vitamins against non-structural ( NSP3 HGNC NSP3 PROTEIN, NSP5 PROTEIN NSP5 HGNC, ORF7a PROTEIN, NSP12 PROTEIN, ORF3a PROTEIN), structural (Spike & Hemagglutinin esterase) and host protein furin HGNC. The in silico analysis exhibited that vitamin B12, Vitamin B9, Vitamin D3 determined suitable binding while vitamin B15 manifested remarkable H-bond interactions with all targets. Vitamin B12 bestowed the lowest energies with human furin HGNC and SARS-COV-2 RNA dependent RNA polymerase PROTEIN. Furin HGNC mediated cleavage of the viral spike glycoprotein PROTEIN is directly related to enhanced virulence of SARS-CoV-2. In contrast to these, vitamin B12 showed zero affinity with SARS-CoV-2 spike PROTEIN protein. These upshots intimate that Vitamin B12 could be the wonder molecule to shrink the virulence by hindering the furin HGNC mediated entry of spike to host cell. These identified molecules may effectively assist in SARS-CoV-2 therapeutic management to boost the immunity by inhibiting the virus imparting relief in lung inflammation MESHD.

    SARS-CoV-2 spike PROTEIN downregulates tetherin HGNC to enhance viral spread

    Authors: Hazel Stewart; Kristoffer H Johansen; Naomi McGovern; Roberta Palmulli; George W Carnell; Jonathan Luke Heeney; Klaus Okkenhaug; Andrew Firth; Andrew A Peden; James R Edgar; Min-Jong Kang; Hyeon Jun Shin; Emiko Mizoguchi; Chun Geun Lee; Jack A. Elias; Ann Moormann; Mireya Wessolossky; Vanni Bucci; Ana Maldonado-Contreras; Michael Chiorazzi; Edwin Ruiz Fuentes; - Yale IMPACT Team; Nathan D Grubaugh; Shelli Farhadian; Charles Dela Cruz; Albert Ko; Wade L Schulz; Aaron M Ring; Shuangge Ma; Saad Omer; Anne L Wyllie; Akiko Iwasaki; Andrew J. Page; Robert A. Kingsley; Gibson Mhlanga

    doi:10.1101/2021.01.06.425396 Date: 2021-01-06 Source: bioRxiv

    The antiviral restriction factor, tetherin HGNC, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin HGNC is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 downregulates tetherin HGNC to aid its release from cells, and investigate potential proteins involved in this process. Loss of tetherin HGNC from cells caused an increase in SARS-CoV-2 viral titre. We find SARS-CoV-2 spike PROTEIN protein to be responsible for tetherin HGNC downregulation, rather than ORF7a PROTEIN as previously described for the 2002-2003 SARS-CoV MESHD. We instead find ORF7a PROTEIN to be responsible for Golgi fragmentation, and expression of ORF7a PROTEIN in cells recapitulates Golgi fragmentation observed in SARS-CoV-2 infected MESHD cells.

    Functional Analysis of SARS-CoV-2 Proteins in Drosophila Identifies Orf6-induced Pathogenicity Attenuated by Selinexor

    Authors: Jun-yi Zhu; Jin-Gu Lee; Joyce van de Leemput; Hangnoh Lee; Zhe Han

    doi:10.21203/rs.3.rs-141269/v1 Date: 2021-01-05 Source: ResearchSquare

    Background: SARS-CoV-2 causes COVID-19 MESHD with a widely diverse disease profile that affect many different tissues. The mechanisms underlying its pathogenicity in host organisms remain unclear. Animal models for study the pathogenicity of SARS-CoV-2 proteins MESHD are lacking. Methods: Using bioinformatic analysis, we showed that the majority of the virus-host interacting proteins are conserved in Drosophila. Therefore, we generated a series of transgenic lines for individual SARS-CoV-2 genes and used the Gal4-UAS system to express them in various tissues to study their pathogenicity. Results: We found that the Nsp6, Orf6 and Orf7a PROTEIN transgenic flies displayed reduced trachea branching MESHD and muscle deficits MESHD resulting in “held-up” wing phenotype and poor climbing ability. Furthermore, muscle tissue in these flies showed dramatically reduced mitochondria. Since Orf6 was found to bind nucleopore proteins XPO1, we tested Selinexor, a drug that inhibits XPO1, and found that it could attenuated the Orf6-induced lethality and tissue-specific phenotypes in flies. Conclusions: Our studies here established new Drosophila models for studying the function of SARS-CoV2 genes, identified Orf6 as a highly pathogenic protein in various tissues, and demonstrated the effects of Selinexor for inhibiting Orf6 toxicity MESHD with an in vivo model system.

    The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children

    Authors: Asmaa Hachim; Haogao Gu; Otared Kavian; Mike YW Kwan; Wai-hung Chan; Yat Sun Yau; Susan S Chiu; Owen TY Tsang; David SC Hui; Fionn Ma; Eric HY Lau; Samuel MS Cheng; Leo LM Poon; Malik JS Peiris; Sophie A Valkenburg; Niloufar Kavian

    doi:10.1101/2021.01.03.21249180 Date: 2021-01-04 Source: medRxiv

    BackgroundChildren are less clinically affected by SARS-CoV-2 infection MESHD than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19 MESHD. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed. MethodsWe tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections MESHD in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 MESHD patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System ( LIPS MESHD). FindingsChildren have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins ( NSP1 HGNC and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b PROTEIN, ORF8 PROTEIN antibodies can discriminate COVID-19 MESHD in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b PROTEIN, NSP1 HGNC, ORF7a PROTEIN and ORF8 PROTEIN. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b PROTEIN antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b PROTEIN, ORF6 PROTEIN and ORF7a PROTEIN. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection MESHD.

    Identification of eight SARS-CoV-2 ORF7a PROTEIN deletion variants in 2,726 clinical specimens

    Authors: Sun Hee Rosenthal; Ron M Kagan; Anna Gerasimova; Ben Anderson; David grover; Michael Hua; Renius Owen; Felicitas Lacbawan; Alicja Piechocka-Trocha; Daniel P. Worrall; Kathryn E. Hall; Musie Ghebremichael; Bruce D. Walker; Xu G. Yu; - MGH COVID-19 Collection & Processing Team; Diane Mathis; Christophe Benoist; Arianne Plaschke; David Eisel; Sarah C. Dany; Stephanie Fesser; Stephanie Erbar; Ferdia Bates; Diana Schneider; Bernadette Jesionek; Bianca Saenger; Ann-Kathrin Wallisch; Yvonne Feuchter; Hanna Junginger; Stefanie A. Krumm; Andre P. Heinen; Petra Adams-Quack; Julia Schlereth; Stefan Schille; Christoph Kroener; Ramon de la Caridad Gueimil Garcia; Thomas Hiller; Leyla Fischer; Rani S. Sellers; Shambhunath Choudhary; Olga Gonzalez; Fulvia Vascotto; Matthew R. Gutman; Jane Fontenot; Shannan Hall-Ursone; Kathleen Brasky; Matthew C Griffor; Seungil Han; Andreas A.H. Su; Joshua Lees; Nicole L. Nedoma; Ellene H. Mashalidis; Parag V. Sahasrabudhe; Charles Y. Tan; Danka Pavliakova; Guy Singh; Camila Fontes-Garfias; Michael Pride; Ingrid L. Scully; Tara Ciolino; Jennifer Obregon; Michal Gazi; Ricardo Carrion Jr.; Kendra J. Alfson; Warren V. Kalina; Deepak Kaushal; Pei-Yong Shi; Thorsten Klamp; Corinna Rosenbaum; Andreas N. Kuhn; Oezlem Tuereci; Philip R. Dormitzer; Kathrin U. Jansen; Ugur Sahin

    doi:10.1101/2020.12.10.418855 Date: 2020-12-11 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) ORF7a PROTEIN, the ortholog of SARS-CoV MESHD ORF7a PROTEIN, is a type I transmembrane protein and plays an important role in virus-host interactions. Deletion variants in ORF7a PROTEIN may influence virulence, but only a few such isolates have been reported. Here, we report 8 unique ORF7a PROTEIN deletion variants of 6 to 96 nucleotides in length identified from 2,726 clinical specimens collected in March of 2020.

    Modest Evolutionary Changes of the SARS-CoV-2 Genome in Bangladesh

    Authors: Sezanur Rahman; Mehedi Hasan; Mohammad Enayet Hossain; Mohammed Ziaur Rahman; Mustafizur Rahman

    doi:10.21203/rs.3.rs-122444/v1 Date: 2020-12-05 Source: ResearchSquare

    Background: The human-to-human transmissive nature of SARS-CoV-2 makes Bangladesh, as well as the other South Asian regions, vulnerable to the ongoing pandemic of COVID-19 MESHD due to their high population densities. The present study was designed based on the genome wide analysis of Bangladeshi and other South Asian isolates. Complete sequences of SARS-CoV-2 were retrieved from the EpiCoV database in order to identify molecular features demonstrating the evolutionary trail and mutation rate.Result: The complete genome mutation rate of the Bangladeshi isolates was estimated to be 0.49E-3 nucleotide substitutions/site/year. A higher mutation rate was found in the non-structural protein-coding genes at: ORF6 PROTEIN (10.29E-3), ORF7a PROTEIN (31.81E-3), and ORF8 PROTEIN (18.35E-3). In contrast, the mutation rates of the structural protein-coding genes were relatively low at: M (1.14E-3), S (1.47E-3), E (3.35E-3), and N (4.59E-3).Conclusions: A comparison of Bangladeshi and other South Asian isolates demonstrated that there were limited mutational changes in the SARS CoV-2 genome. Knowledge of the Southeast Asian SARS CoV-2 evolutionary genome will help in selecting future vaccine candidates and designing therapeutic drug targets.

    Horizontal gene transfer and recombination analysis of SARS-CoV-2 genes helps discover its close relatives and shed light on its origin

    Authors: Vladimir Makarenkov; Bogdan Mazoure; Guillaume Rabusseau; Pierre Legendre; Gustavo Ferrer; Xiaoping Jiang; Ya-Nan Dai; Haiyan Zhao; Lucas Adams; Michael Holtzman; Adam Bailey; James Brett Case; Daved Fremont; Robyn S Klein; Michael Diamond; Adrianus Boon

    doi:10.1101/2020.12.03.410233 Date: 2020-12-03 Source: bioRxiv

    The SARS-CoV-2 pandemic is among the most dangerous infectious diseases that have emerged in recent history. Human CoV strains discovered during previous SARS outbreaks have been hypothesized to pass from bats to humans using intermediate hosts, e.g. civets for SARS-CoV MESHD and camels for MERS-CoV. The discovery of an intermediate host of SARS-CoV-2 and the identification of specific mechanism of its emergence in humans are topics of primary evolutionary importance. In this study we investigate the evolutionary patterns of 11 main genes of SARS-CoV-2. Previous studies suggested that the genome of SARS-CoV-2 is highly similar to the horseshoe bat coronavirus RaTG13 for most of the genes and to some Malayan pangolin coronavirus MESHD (CoV) strains for the receptor binding (RB) domain of the spike protein PROTEIN. We provide a detailed list of statistically significant horizontal gene transfer and recombination events (both intergenic and intragenic) inferred for each of 11 main genes of the SARS-Cov-2 genome. Our analysis reveals that two continuous regions of genes S and N of SARS-CoV-2 may result from intragenic recombination between RaTG13 and Guangdong (GD) Pangolin CoVs. Statistically significant gene transfer-recombination events between RaTG13 and GD Pangolin CoV MESHD have been identified in region [1215-1425] of gene S and region [534-727] of gene N PROTEIN. Moreover, some significant recombination events between the ancestors of SARS-CoV-2, RaTG13, GD Pangolin CoV MESHD and bat CoV ZC45-ZXC21 coronaviruses have been identified in genes ORF1ab PROTEIN, S, ORF3a PROTEIN, ORF7a PROTEIN, ORF8 PROTEIN and N. Furthermore, topology-based clustering of gene trees inferred for 25 CoV organisms revealed a three-way evolution of coronavirus genes, with gene phylogenies of ORF1ab PROTEIN, S and N forming the first cluster, gene phylogenies of ORF3a PROTEIN, E, M, ORF6 PROTEIN, ORF7a PROTEIN, ORF7b PROTEIN and ORF8 PROTEIN forming the second cluster, and phylogeny of gene ORF10 PROTEIN forming the third cluster. The results of our horizontal gene transfer and recombination analysis suggest that SARS-Cov-2 could not only be a chimera resulting from recombination of the bat RaTG13 and Guangdong pangolin coronaviruses but also a close relative of the bat CoV ZC45 and ZXC21 strains. They also indicate that a GD pangolin may be an intermediate host of SARS-CoV-2.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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