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Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF7b (13)

ORF8 (8)

ORF7a (7)

ORF6 (6)

ORF10 (6)


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SARS-CoV-2 Proteins
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    Genomic monitoring unveil the early detection of the SARS-CoV-2 B.1.351 lineage (20H/501Y.V2) in Brazil

    Authors: Svetoslav N Slavov PhD; Jose Patane PhD; Rafael S Bezerra BSc; Marta Giovanetti PhD; Vagner Fonseca MSc; Antonio J Martins PhD; Vincent L Viala PhD; Evandra S Rodrigues PhD; Elaine V Santos PhD; Claudia R.S Barros PhD; Elaine C Marqueze PhD; Bibiana Santos MSc; Flavia Aburjaile PhD; Raul M Neto PhD; Debora B Moretti PhD; Ricardo Haddad MSc; Rodrigo T Calado PhD; Joao Paulo Kitajima PhD; Erika Freitas PhD; David Schlesinger PhD; Luiz C.J Alcantara PhD; M. Carolina Elias PhD; Sandra C.S Vessoni PhD; Simone Kashima PhD; Dimas T Covas Md-PhD

    doi:10.1101/2021.03.30.21254591 Date: 2021-04-04 Source: medRxiv

    Sao Paulo State, the most populous area in Brazil, currently experiences a second wave of the COVID-19 pandemic MESHD which overwhelmed the healthcare system. Recently, due to the paucity of SARS-CoV-2 MESHD complete genome sequences, we established a Network for Pandemic Alert of Emerging SARS-CoV-2 Variants to rapidly understand the spread of SARS-CoV-2 and monitor in nearly real-time the circulating SARS-CoV-2 variants into the state. Through full genome analysis of 217 SARS-CoV-2 complete genome sequences obtained from the largest regional health departments we were able to identify the co-circulation of multiple SARS-CoV-2 lineages such as i) B.1.1 (0.92%), ii) B.1.1.1 (0.46%), iii) B.1.1.28 (25.34%), iv) B.1.1.7 (5.99%), v) B.1.566 (1.84%), vi) P.1 (64.05%), and P.2 (0.92%). Further our analysis allowed the detection, for the first time in Brazil of the South African variant of concern (VOC), the B.1.351 (501Y.V2) (0.46%). The identified lineage was characterized by the presence of the following mutations: ORF1ab PROTEIN: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; Spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F; ORF3a PROTEIN: Q57H, S171L, E: P71L; ORF7b PROTEIN: Y10F, N: T205I; ORF14: L52F. Origin of the most recent common ancestor of this genomic variant was inferred to be between middle October to late December 2020. Analysis of generated sequences demonstrated the predominance of the P.1 lineage and allowed the early detection of the South African strain for the first time in Brazil. Our findings highlight the importance to increase active monitoring to ensure the rapid detection of new SARS-CoV-2 variants with a potential impact in pandemic control and vaccination strategies.

    Targeting CTP Synthetase 1 HGNC to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection MESHD

    Authors: Youliang Rao; Ting-Yu Wang; Chao Qin; Bianca Espinosa; Qizhi Liu; Arunika Ekanayake; Jun Zhao; Ali Can Savas; Shu Zhang; Mehrnaz Zarinfar; Yongzhen Liu; Wenjie Zhu; Nicholas Alexander Graham; Taijiao Jiang; Chao Zhang; Pinghui Feng

    doi:10.1101/2021.02.05.429959 Date: 2021-02-07 Source: bioRxiv

    The newly emerged SARS-CoV-2 caused a global pandemic with astonishing mortality and morbidity. The mechanisms underpinning its highly infectious nature remain poorly understood. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 HGNC ( CTPS1 HGNC) to promote CTP synthesis and suppress interferon ( IFN HGNC) induction. Screening a SARS-CoV-2 expression library identified ORF7b PROTEIN and ORF8 PROTEIN that suppressed IFN HGNC induction via inducing the deamidation of interferon regulatory factor 3 HGNC ( IRF3 HGNC). Deamidated IRF3 HGNC fails to bind the promoters of classic IRF3 HGNC-responsible genes, thus muting IFN HGNC induction. Conversely, a shRNA-mediated screen focused on cellular glutamine amidotransferases corroborated that CTPS1 HGNC deamidates IRF3 HGNC to inhibit IFN HGNC induction. Functionally, ORF7b PROTEIN and ORF8 PROTEIN activate CTPS1 HGNC to promote de novo CTP synthesis while shutting down IFN HGNC induction. De novo synthesis of small-molecule inhibitors of CTPS1 HGNC enabled CTP depletion and IFN HGNC induction in SARS-CoV-2 infection MESHD, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabolic activation to fuel viral replication. Inhibition of the cellular CTPS1 HGNC offers an attractive means for developing antiviral therapy that would be resistant to SARS-CoV-2 mutation.

    SARS-CoV-2 ORF7b PROTEIN: is a bat virus protein homologue a major cause of COVID-19 MESHD symptoms?

    Authors: Marie-Laure Fogeron; Roland Montserret; Johannes Zehnder; Minh-Ha Nguyen; Marie Dujardin; Louis Brigandat; Laura Cole; Marti Ninot-Pedrosa; Lauriane Lecoq; Beat H Meier; Anja Bockmann

    doi:10.1101/2021.02.05.428650 Date: 2021-02-05 Source: bioRxiv

    ORF7b PROTEIN is an accessory protein of SARS-CoV-2, the virus behind the COVID-19 pandemic MESHD. Using cell-free synthesized ORF7b PROTEIN, we experimentally show that ORF7b PROTEIN assembles into stable multimers. The ORF7b PROTEIN sequence shows a transmembrane segment, which multimerizes through a leucine zipper. We hypothesize that ORF7b PROTEIN has the potential to interfere with important cellular processes that involve leucine-zipper formation, and present two particularly striking examples. First, leucine zippers are central in heart rhythm regulation through multimerization of phospholamban in cardiomyocytes. Second, epithelial cell-cell adhesion relies on E-cadherins, which dimerize using a transmembrane leucine zipper. Most common symptoms of SARS-CoV-2 infection MESHD, including heart arrythmias MESHD, odor loss MESHD, impaired oxygen uptake and intestinal problems, up to multiorgan failure MESHD, can be rationalized by a possible interference of ORF7b PROTEIN with the functions of these proteins. We ask whether this is pure coincidence, or whether our observations point to disruption by ORF7b PROTEIN of vital processes in COVID-19 MESHD.

    Designing a new multi epitope-based vaccine against COVID-19 MESHD disease: an immunoinformatic study based on reverse vaccinology approach

    Authors: Afshin Samimi Nemati; Majid Tafrihi; Fatemeh Sheikhi; Abolfazl Rostamian Tabari; Amirhossein Haditabar

    doi:10.21203/rs.3.rs-206270/v1 Date: 2021-02-04 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has currently caused a significant pandemic among worldwide populations. The transmission speed and the high rate of mortality caused by the disease necessitate studies for the rapid designing and effective vaccine production. The purpose of this study is to predict and design a novel multi-epitope vaccine against the SARS-CoV-2 virus using bioinformatics approaches. Coronavirus envelope proteins PROTEIN, ORF7b PROTEIN, ORF8 PROTEIN, ORF10 PROTEIN, and NSP9 PROTEIN were selected as targets for epitope mapping using IEDB and BepiPred 2.0 Servers. Also, molecular docking studies were performed to determine the candidate vaccine's affinity to TLR3 HGNC, TLR4 HGNC, MHC I, and MHC II molecules. Thirteen epitopes were selected to construct the multi-epitope vaccine. We found that the constructed peptide has valuable antigenicity, stability, and appropriate half-life. The Ramachandran plot approved the quality of the predicted model after the refinement process. Molecular docking investigations revealed that antibody-mode in the Cluspro 2.0 server showed the lowest binding energy for MHCI, MHCII, TLR3 HGNC, and TLR4 HGNC. This study confirmed that the designed vaccine has a good antigenicity and stability and could be a proper vaccine candidate against the COVID-19 MESHD infectious disease MESHD though, in vitro and in vivo experiments are necessary to complete and confirm our results.

    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.

    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.

    SARS-CoV-2 antibody signatures for predicting the outcome of COVID-19 MESHD

    Authors: Qing Lei; Caizheng Yu; Yang Li; Hongyan Hou; Zhaowei Xu; Meian He; Ziyong Sun; Feng Wang; Sheng-ce Tao; Xionglin Fan

    doi:10.1101/2020.11.10.20228890 Date: 2020-11-13 Source: medRxiv

    The COIVD-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for predicting the outcome of COVID-19 MESHD. Growing evidences have revealed that SARS-CoV-2 specific antibodies remain elevated with disease progression and severity in COIVD-19 patients. We assumed that antibodies may serve as biomarkers for predicting disease outcome. By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgM/ IgG responses against 20 SARS-CoV-2 proteins in 1,034 hospitalized COVID-19 MESHD patients on admission, who were followed till 66 days. The microarray results were correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 MESHD mortality. We found that high level of IgM against ORF7b PROTEIN at the time of hospitalization is an independent predictor of patient survival (p trend = 0.002), while levels of IgG responses to 6 non-structural proteins PROTEIN and 1 accessory protein, i. e PROTEIN., NSP4 HGNC NSP4 PROTEIN, NSP7 PROTEIN, NSP9 PROTEIN, NSP10 PROTEIN, RdRp PROTEIN ( NSP12 PROTEIN), NSP14 PROTEIN, and ORF3b PROTEIN, possess significant predictive power for patient death MESHD, even after further adjustments for demographics, comorbidities, and common laboratory markers for disease severity (all with p trend < 0.05). Spline regression analysis indicated that the correlation between ORF7b PROTEIN IgM, NSP9 PROTEIN IgG, and NSP10 PROTEIN IgG and risk of COVID-19 MESHD mortality is linear (p = 0.0013, 0.0073 and 0.0003, respectively). Their AUCs for predictions, determined by computational cross-validations (validation1), were 0.74 (cut-off = 7.59), 0.66 (cut-off = 9.13), and 0.68 (cut-off = 6.29), respectively. Further validations were conducted in the second and third serial samples of these cases (validation2A, n = 633, validation2B, n = 382), with high accuracy of prediction for outcome. These findings have important implications for improving clinical management, and especially for developing medical interventions and vaccines.

    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.

    SARS-CoV-2 genomes from Oklahoma, USA

    Authors: Sai Narayanan; John Corban Ritchey; Girish Patil; Narasaraju Teluguakula; Sunil More; Jerry Malayer; Jeremiah Saliki; Anil Kaul; Akhilesh Ramachandran

    doi:10.1101/2020.09.15.20195420 Date: 2020-09-18 Source: medRxiv

    Genomic sequencing has played a major role in understanding the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the current pandemic, it is essential that SARS-CoV-2 viruses are sequenced regularly to determine mutations and genomic modifications in different geographical locations. In this study we sequenced SARS-CoV-2 from 5 clinical samples obtained in Oklahoma, USA during different time points of pandemic presence in the state. One sample from the initial days of the pandemic in the state and 4 during the peak in Oklahoma were sequenced. Previously reported mutations including D614G in S gene, P4715L in ORF1ab PROTEIN, S194L, R203K and G204R in N gene PROTEIN were identified in the genomes sequenced in this study. Possible novel mutations were also detected such as G1167V in S gene, A6269S and P3371S in ORF1ab PROTEIN, T28I in ORF7b PROTEIN, G96R in ORF8 PROTEIN. Phylogenetic analysis of the genomes showed similarity to viruses from across the globe. These novel mutations and phylogenetic analysis emphasize the contagious nature of the virus.

    Mutational Analysis of SARS-CoV-2 Genome in African Population

    Authors: Olabode E. Omotoso; Ayoade Desmond Babalola; Amira Matareek; Lele Zhao; Virginia Ledda; Lucie Abeler- Dorner; Michelle Kendall; Anel Nurtay; Hao-Yuan Cheng; Ta-Chou Ng; Hsien-Ho Lin; Rob Hinch; Joanna Masel; A. Marm Kilpatrick; Christophe Fraser; Raquel Gonzalez Seoane; Clara Martinez Diago; Esther Canedo Carballeira; Macarena Alferez Alvarez Mallo; Cristina Casanova Pedraz; Onofre Alomar Mateu; Cristina Lesmes Heredia; Juan Carlos Wizner de Alva; Ruth Bernardo Vega; Montserrat Macia Badia; Cristina Alvarez Colomo; Antonio Sanchez Munoz; Laia Pratcorona Alicart; Ruben Alonso Saiz; Monica Lopez Rodriguez; Maria Carmen Barbancho Lopez; Marta Meca Casbas; Oscar Vaquerizo Ruiz; Eva Moran Antolin; Maria Jose Nunez Valera; Camino Fernandez Fernandez; Albert Tubau Navarra; Alejandra M Cano Garcia; Carmen Baena Luque; Susana Soldevilla Perez; Irene Gastaca Abasolo; Jose Adanez Garcia; Maria Teulon Gonzalez; Alberto Puertas Prieto; Rosa Ostos; Maria del Pilar Guadix Martin; Monica Catalina Coello; Maria Luisa De la Cruz Conti; Africa Cano Aguilar; Jose A Sainz Bueno

    doi:10.1101/2020.09.07.286088 Date: 2020-09-07 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly infectious and pathogenic virus has claimed lot of lives globally since its outbreak in December 2019 posing dire threat on public health, global economy, social and human interaction. At moderate rate, mutations in the SARS-CoV-2 genome are evolving which might have contributed to viral genome variability, transmission, replication efficiency and virulence in different regions of the world. The present study elucidated the mutational landscape in SARS-CoV-2 genome among the African population, which may have contributed to the virulence, pathogenicity and transmission observed in the region. Multiple sequence alignment of the SARS-CoV-2 genome (356 viral protein sequences) was performed using ClustalX version 2.1 and phylogenetic tree was built using Molecular Evolutionary Genetics Analysis (MEGA) X software. ORF1ab PROTEIN polyprotein, spike glycoprotein PROTEIN, ORF3 HGNC, ORF8 PROTEIN and nucleocapsid phosphoprotein were observed as mutational hotspots in the African population and may be of keen interest in the adaptability of SARS-CoV-2 to the human host. While, there is conservation in the envelope protein PROTEIN, membrane glycoprotein PROTEIN, ORF6 PROTEIN, ORF7a PROTEIN, ORF7b PROTEIN and ORF10 PROTEIN. The accumulation of moderate mutations (though slowly) in the SARS-CoV-2 genome as revealed in our study, could be a promising strategy to develop drugs or vaccines with respect to the viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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