Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF6 (26)

ORF8 (10)

ORF7a (10)

ORF3a (7)

ORF7b (6)


SARS-CoV-2 Proteins
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    Contribution of SARS-CoV-2 accessory proteins to viral pathogenicity in K18 hACE2 HGNC transgenic mice


    doi:10.1101/2021.03.09.434696 Date: 2021-03-12 Source: bioRxiv

    Severe Acute Respiratory Syndrome coronavirus 2 MESHD (SARS-CoV-2) is the viral pathogen responsible for the current coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. To date, it is estimated that over 113 million individuals have been infected with SARS-CoV-2 and over 2.5 million human deaths have been recorded worldwide. Currently, three vaccines have been approved by the Food and Drug Administration for emergency use only. However much of the pathogenesis observed during SARS-CoV-2 infection MESHD remains elusive. To gain insight into the contribution of individual accessory open reading frame (ORF) proteins in SARS-CoV-2 pathogenesis, we used our recently described reverse genetics system approach to successfully engineer recombinant (r)SARS-CoV-2, where we individually removed viral 3a, 6, 7a, 7b, and 8 ORF proteins, and characterized these recombinant viruses in vitro and in vivo. Our results indicate differences in plaque morphology, with ORF deficient MESHD (DORF) viruses producing smaller plaques than those of the wild-type (rSARS-CoV-2/WT). However, growth kinetics of DORF viruses were like those of rSARS-CoV-2/WT. Interestingly, infection of K18 HGNC human angiotensin converting enzyme 2 HGNC ( hACE2 HGNC) transgenic mice with the DORF rSARS-CoV-2 identified ORF3a PROTEIN and ORF6 PROTEIN as the major contributors of viral pathogenesis, while DORF7a, DORF7b and DORF8 rSARS-CoV-2 induced comparable pathology to rSARS-CoV-2/WT. This study demonstrates the robustness of our reverse genetics system to generate rSARS-CoV-2 and the major role for ORF3a PROTEIN and ORF6 PROTEIN in viral pathogenesis, providing important information for the generation of attenuated forms of SARS-CoV-2 for their implementation as live-attenuated vaccines for the treatment of SARS-CoV-2 infection MESHD and associated COVID-19 MESHD.

    SARS-CoV-2 ORF6 PROTEIN disturbs nucleocytoplasmic trafficking to advance the viral replication

    Authors: Yoichi Miyamoto; Yumi Itoh; Tatsuya Suzuki; Tomohisa Tanaka; Yusuke Sakai; Masaru Koido; Chiaki Hata; Cai-Xia Wan; Mayumi Otani; Kohji Moriishi; Taro Tachibana; Yoichiro Kamatani; Yoshihiro Yoneda; Toru Okamoto; Masahiro Oka

    doi:10.1101/2021.02.24.432656 Date: 2021-02-24 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the virus responsible for the coronavirus disease 2019 MESHD pandemic. ORF6 PROTEIN is known to antagonize the interferon signaling by inhibiting the nuclear translocation of STAT1 HGNC. Here we show that ORF6 PROTEIN acts as a virulence factor through two distinct strategies. First, ORF6 PROTEIN directly interacts with STAT1 HGNC in an IFN HGNC-independent manner to inhibit its nuclear translocation. Second, ORF6 PROTEIN directly binds to importin 1 HGNC, which is a nuclear transport factor encoded by KPNA2 HGNC, leading to a significant suppression of importin 1 HGNC-mediated nuclear transport. Furthermore, we found that KPNA2 HGNC knockout enhances the viral replication, suggesting that importin 1 HGNC suppresses the viral propagation. Additionally, the analyses of gene expression data revealed that importin 1 HGNC levels decreased significantly in the lungs of older individuals. Taken together, SARS-CoV-2 ORF6 PROTEIN disrupts the nucleocytoplasmic trafficking to accelerate the viral replication, resulting in the disease progression, especially in older individuals.

    The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation


    doi:10.1101/2021.02.23.432450 Date: 2021-02-23 Source: bioRxiv

    Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 MESHD severity, including the TRIM4 HGNC interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein PROTEIN. Viral NSP1 HGNC protein adjacency to the EIF3 HGNC complex was associated with inhibited host protein translation whereas ORF6 PROTEIN localization with MAVS HGNC was associated with inhibited RIG-I HGNC 2CARD-mediated IFNB1 HGNC promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 HGNC NSP5 PROTEIN protease, with specific functional cleavage sequences in host proteins CWC22 HGNC and FANCD2 HGNC. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2. Author SummarySARS-CoV-2 is the latest pathogenic coronavirus to emerge as a public health threat. We create a database of proximal host proteins to 17 SARS-CoV-2 viral proteins. We validate that NSP1 HGNC is proximal to the EIF3 HGNC translation initiation complex and is a potent inhibitor of translation. We also identify ORF6 PROTEIN antagonism of RNA-mediate innate immune signaling. We produce a database of potential host targets of the viral protease NSP5 HGNC NSP5 PROTEIN, and create a fluorescence-based assay to screen cleavage of peptide sequences. We believe that this data will be useful for identifying roles for many of the uncharacterized SARS-CoV-2 proteins and provide insights into the pathogenicity of new or emerging coronaviruses.

    SARS-CoV-2 Mutations in Brazil: From Genomics to Clinical Conditions

    Authors: Luis Timmers; Julia Peixoto; Rodrigo Ducati; Jose Fernando Bachega; Leandro Mattos Pereira; Rafael Andrade Caceres; Fernanda Majolo; Guilherme Liberato Da Silva; Debora Bublitz Anton; Marcia Inês Goettert; Odir Antônio Dellagostin; Joao Henriques; Leder Xavier; Stefan Laufer

    doi:10.26434/chemrxiv.14045783.v1 Date: 2021-02-19 Source: ChemRxiv

    Due to the high rate of transmissibility, Brazil became the new COVID-19 MESHD outbreak epicenter, being a reference region to monitor how SARS-CoV-2 is mutating and spreading. Here, we combined genomic and structural biology analysis evaluate genomes isolated from different regions of Brazil. We showed that the most prevalent mutations were located in the S, N, ORF3a PROTEIN and ORF6 PROTEIN genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, helping studies of structure-based drug discovery and vaccine development.

    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.

    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/ 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.

    Hacking the diversity of SARS-CoV-2 and SARS-like coronaviruses in human, bat and pangolin populations

    Authors: Nicholas John Dimonaco; Mazdak Salavati; Barbara Shih; Konrad Scheffler; Joel O. Wertheim; Clive M Brown; Martin S Cetron; Francisco Alvarado-Ramy; Stephen Hwang; Mohamed Sahl; Jinan Suliman; Elias Tayar; Hasan Ali Kasem; Meynard J. A. Agsalog; Bassam K. Akkarathodiyil; Ayat A. Alkhalaf; Mohamed Morhaf M. H. Alakshar; Abdulsalam Ali A. H. Al-Qahtani; Monther H. A. Al-Shedifat; Anas Ansari; Ahmad Ali Ataalla; Sandeep Chougule; Abhilash K. K. V. Gopinathan; Feroz J. Poolakundan; Sanjay U. Ranbhise; Saed M. A. Saefan; Mohamed M. Thaivalappil; Abubacker S. Thoyalil; Inayath M. Umar; Zaina Al Kanaani; Abdullatif Al Khal; Einas Al Kuwari; Adeel A. Butt; Peter Coyle; Andrew Jeremijenko; Anvar Hassan Kaleeckal; Ali Nizar Latif; Riyazuddin Mohammad Shaik; Hanan F. Abdul Rahim; Hadi M. Yassine; Gheyath K. Nasrallah; Mohamed G. Al Kuwari; Odette Chaghoury; Hiam Chemaitelly; Laith J Abu-Raddad

    doi:10.1101/2020.11.24.391763 Date: 2020-11-24 Source: bioRxiv

    In 2019, a novel coronavirus, SARS-CoV-2/nCoV-19, emerged in Wuhan, China, and has been responsible for the current COVID-19 pandemic MESHD. The evolutionary origins of the virus remain elusive and understanding its complex mutational signatures could guide vaccine design and development. As part of the international "CoronaHack" in April 2020 (, we employed a collection of contemporary methodologies to compare the genomic sequences of coronaviruses isolated from human (SARS-CoV-2;n=163), bat (bat-CoV;n=215) and pangolin (pangolin-CoV;n=7) available in public repositories. Following de novo gene annotation prediction, analysis on gene-gene similarity network, codon usage bias and variant discovery were carried out. Strong host-associated divergences were noted in ORF3a PROTEIN, ORF6 PROTEIN, ORF7a PROTEIN, ORF8 PROTEIN and S, and in codon usage bias profiles. Lastly, we have characterised several high impact variants (inframe insertion/deletion or stop gain) in bat-CoV and pangolin-CoV populations, some of which are found in the same amino acid position and maybe highlighting loci of potential functional relevance.

    Gene Expression Meta-Analysis Identifies Molecular Changes Associated with SARS-CoV Infection in Lungs

    Authors: Amber Park; Laura Harris; Tanushka Doctor; Neda Nasheri; Hua Wang; Xuemei Feng; Gennadiy Zelinskyy; Mirko Trilling; Kathrin Sutter; Mengji Lu; Baoju Wang; Dongliang Yang; Xin Zheng; Jia Liu; Davey Smith; Daniela Weiskopf; Alessandro Sette; Shane Crotty; Jian Jin; Xian Chen; Andrew Pekosz; Sabra Klein; Irina Burd

    doi:10.1101/2020.11.14.382697 Date: 2020-11-16 Source: bioRxiv

    Background: Severe Acute Respiratory Syndrome MESHD (SARS) corona virus ( SARS-CoV) infections MESHD are a serious public health threat because of their pandemic-causing potential. This work uses mRNA expression data to predict genes associated with SARS-CoV infection MESHD through an innovative meta-analysis examining gene signatures (i. e., gene PROTEIN lists ranked by differential gene expression between SARS and mock infection MESHD). Methods: This work defines 29 gene signatures representing SARS infection MESHD across seven strains with established mutations that vary virulence (infectious clone SARS (icSARS), Urbani, MA15, {Delta} ORF6 PROTEIN, BAT-SRBD, {Delta} NSP16 PROTEIN, and ExoNI) and host (human lung cultures and/or mouse lung samples) and examines them through Gene Set Enrichment Analysis (GSEA). To do this, first positive and negative icSARS gene panels were defined from GSEA-identified leading-edge genes between 500 genes from positive or negative tails of the GSE47960-derived icSARSvsmock signature and the GSE47961-derived icSARSvsmock signature, both from human cultures. GSEA then was used to assess enrichment and identify leading-edge icSARS panel genes in the other 27 signatures. Genes associated with SARS-CoV infection MESHD are predicted by examining membership in GSEA-identified leading-edges across signatures. Results: Significant enrichment (GSEA p<0.001) was observed between GSE47960-derived and GSE47961-derived signatures, and those leading-edges defined the positive (233 genes) and negative (114 genes) icSARS panels. Non-random (null distribution p<0.001) significant enrichment (p<0.001) was observed between icSARS panels and all verification icSARSvsmock signatures derived from human cultures, from which 51 over- and 22 under-expressed genes were shared across leading-edges with 10 over-expressed genes already being associated with icSARS infection MESHD. For the icSARSvsmock mouse signature, significant, non-random enrichment (both p<0.001) held for only the positive icSARS panel, from which nine genes were shared with icSARS infection MESHD in human cultures. Considering other SARS strains, significant (p<0.01), non-random (p<0.002) enrichment was observed across signatures derived from other SARS strains for the positive icSARS panel. Five positive icSARS panel genes, CXCL10, OAS3, OASL, IFIT3, and XAF1, were found in mice and human signatures. Conclusion: The GSEA-based meta-analysis approach used here identified genes with and without reported associations with SARS-CoV infections MESHD, highlighting this approachs predictability and usefulness in identifying genes that have potential as therapeutic targets to preclude or overcome SARS infections MESHD.

    Variability of Accessory Proteins Rules the SARS-CoV-2 Pathogenicity

    Authors: Sk. Sarif Hassan; Pabitra Pal Choudhury; Vladimir N Uversky; Guy W. Dayhoff II; Alaa A. A. Aljabali; Bruce Uhal; Kenneth Lundstrom; Murat Seyran; Damiano Pizzol; Parise Adadi; Amos Lal; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-da-Cruz; Kazuo Takayama; Angel Serrano Aroca; Gaurav Chauhan; Giorgio Palu; Adam Brufsky

    doi:10.1101/2020.11.06.372227 Date: 2020-11-08 Source: bioRxiv

    The coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) which is pandemic with an estimated fatality rate less than 1% is ongoing. SARS-CoV-2 accessory proteins ORF3a PROTEIN, ORF6 PROTEIN, ORF7a PROTEIN, ORF7b PROTEIN, ORF8 PROTEIN, and ORF10 PROTEIN with putative functions to manipulate host immune mechanisms such as interferons, immune signaling receptor NLRP3 HGNC ( NOD HGNC-, LRR-, and pyrin domain-containing 3) inflammasome, inflammatory cytokines such as interleukin {beta} ( IL-1{beta HGNC}) are critical in COVID-19 MESHD pathology. Outspread variations of each of the six accessory proteins of all complete proteomes (available as of October 26, 2020, in the National Center for Biotechnology Information depository) of SARS-CoV-2, were observed across six continents. Across all continents, the decreasing order of percentage of unique variations in the accessory proteins was found to be ORF3a PROTEIN> ORF8 PROTEIN> ORF7a PROTEIN> ORF6 PROTEIN> ORF10 PROTEIN> ORF7b PROTEIN. The highest and lowest unique variations of ORF3a PROTEIN were observed in South America and Oceania, respectively. This finding suggests that the wide variations of accessory proteins seem to govern the pathogenicity of SARS-CoV-2, and consequently, certain propositions and recommendations can be made in the public interest.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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