Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (3)

NSP1 (2)

ProteinS (2)

ORF8 (2)

ORF1a (1)


SARS-CoV-2 Proteins
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    New-Onset IgG Autoantibodies in Hospitalized Patients with COVID-19 MESHD

    Authors: Sarah Esther Chang; Allan Feng; Wenzhao Meng; Sokratis Apostolidis; Elisabeth Mack; Maja Artandi; Linda Barman; Kate Bennett; Saborni Chakraborty; Iris Chang; Peggie Cheung; Sharon Chinthrajah; Shaurya Dhingra; Evan Do; Amanda Finck; Andrew Gaano; Reinhard Gessner; Heather M. Giannini; Joyce Gonzalez; Sarah Greib; Margrit Guendisch; Alex Ren Hsu; Alex Kuo; Monali Manohar; Rong Mao; Indira Neeli; Andreas Neubauer; Oluwatosin Oniyide; Abigail Elizabeth Powell; Rajan Puri; Harald Renz; Jeffrey M. Schapiro; Payton Anders Weidenbacher; Rich Wittman; Neera Ahuja; Ho-Ryun Chung; Prasanna Jagannathan; Judith James; Peter S. Kim; Nuala J. Meyer; Kari Christine Nadeau; Marko Radic; William H. Robinson; Upinder Singh; Taia T. Wang; E. John Wherry; Chrysanthi Skevaki; Eline T. Luning Prak; Paul J Utz

    doi:10.1101/2021.01.27.21250559 Date: 2021-01-29 Source: medRxiv

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD), caused by Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2), is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. We developed three different protein arrays to measure hallmark IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 MESHD patients in three different centers. Autoantibodies were identified in approximately 50% of patients, but in <15% of healthy controls. When present, autoantibodies largely targeted autoantigens associated with rare disorders such as myositis MESHD, systemic sclerosis MESHD and CTD overlap syndromes. Anti-nuclear antibodies (ANA) were observed in ~25% of patients. Patients with autoantibodies tended to demonstrate one or a few specificities whereas ACA were even more prevalent, and patients often had antibodies to multiple cytokines. Rare patients were identified with IgG antibodies against angiotensin converting enzyme-2 ( ACE-2 HGNC). A subset of autoantibodies and ACA developed de novo following SARS-CoV-2 infection MESHD while others were transient. Autoantibodies tracked with longitudinal development of IgG antibodies that recognized SARS-CoV-2 structural proteins such as S1 PROTEIN, S2, M, N and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. COVID-19 MESHD patients with one or more autoantibodies tended to have higher levels of antibodies against SARS-CoV-2 Nonstructural Protein 1 ( NSP1 HGNC) and Methyltransferase (ME). We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 MESHD patients and are positively correlated with immune responses to SARS-CoV-2 proteins MESHD.

    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.

    Novel Mutations in NSP1 HGNC and PLPro of SARS-CoV-2 NIB-1 Genome Mount for Effective Therapeutics

    Authors: Mohammad Uzzal Hossain; Arittra Bhattacharjee; Md. Tabassum Hossain Emon; Zeshan Mahmud Chowdhury; Md. Golam Mosaib; Md. Moniruzzaman; Md. Hadisur Rahman; Md. Nazrul Islam; Irfan Ahmed; Md. Ruhul Amin; Asif Rashed; Keshob Chandra Das; Chaman Ara Keya; Md. Salimullah; Maria Elvira Balcells; Luis Rojas; Bruno Nervi; Jyh Kae Nien; Javier Garate; Carolina Prieto; Sofia Palma; Carolina Escobar; Josefina bascunan; Rodrigo Munoz; Monica Pinto; Daniela Cardemil; Marcelo Navarrete; Soledad Reyes; Victoria Espinoza; Nicolas Yanez; Christian Caglevic

    doi:10.1101/2020.12.02.408229 Date: 2020-12-02 Source: bioRxiv

    Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2), the etiologic agent of Coronavirus Disease MESHD- 2019 ( COVID-19 MESHD), is rapidly accumulating new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Recently, we have reported a Sanger method based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel mutations in V121D, V843F, A889V and G1691C positions. V121D substitution has the potential to destabilize the Non-Structural Protein ( NSP-1 HGNC) which inactivates the type-1 Interferon-induced antiviral system hence this mutant could be the basis of attenuated vaccines against SARS-CoV-2. V843F, A889V and G1691C are all located in NSP3 PROTEIN NSP3 HGNC. G1691C can decrease the flexibility of the protein while V843F and A889V changed the binding pattern of SARS-CoV-2 Papain MESHD Papain-Like protease PROTEIN (PLPro) inhibitor GRL0617. V843F PLPro showed reduced affinity for Interferon Stimulating Gene-15 ( ISG-15 HGNC) protein whereas V843F+A889V double mutants exhibited the same binding affinity as wild type PLPro. Here, V843F is a conserved position of PLPro that damaged the structure but A889V, a less conserved residue, most probably neutralized that damage. Mutants of NSP1 HGNC could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro could be targeted to develop anti-SARS therapeutics.

    In Silico studies of Natural compounds that inhibit SARS-CoV-2 Nucleocapsid Nsp1 HGNC/ Nsp3 HGNC proteins mediated Viral Replication and Pathogenesis

    Authors: Hemanth Kumar Manikyam

    doi:10.21203/ Date: 2020-11-05 Source: ResearchSquare

    Highly Transmissible and pathogenic coronavirus that emerged in late December of 2019 caused Severe acute respiratory syndrome MESHD (SARS-CoV-2), which challenged human health and public safety. Severity of the disease depends on the viral load and the type of mutation that occurred in the coronavirus. Nonstructural proteins like, Nsp1 HGNC, Nsp3 HGNC, Nsp12 and Nsp13 including other viral proteins plays important role during viral replication life cycle. Viral Replication initiated by hacking the host cellular mechanism either by synergy or by suppression using nucleocapsid proteins PROTEIN of the virus. Spike (S) protein PROTEIN of the SARS-CoV-2 uses angiotensin-converting enzyme II ( ACE2 HGNC) and TRMPSS as a cell entry. Once virus enters host cell, nucleocapsid proteins PROTEIN along with its genome is releases from endosomes into cytosol of the host cell. Ca2+/ CaM HGNC ( Calmodulin HGNC)/Calcineurin complex of the host cell plays important role during viral replication which is mediated by nucleocapsid proteins PROTEIN of the virus. Nsp1 HGNC/ Nsp3 HGNC nonstructural proteins triggers synergetic activity with CD147 HGNC/ CyPA HGNC/ HSPG HGNC pathway and TRMP2/ADPr/Ca+2 mediated Ca2+/CaM ( Calmodulin HGNC)/Calcineurin synthesis and free radicle generation in mitochondria leading to viral replication and severe chemokine activation pathways. Docking studies were carried out to inhibit Cyclophilin A and TRMP2 proteins as drug targets. Natural compounds like Withanolide A, Columbin, Cucurbitacin E, Boswellic acid along with Cyclosporines, Vitamin E and N-Acetyl cysteine ( NAC HGNC) were selected as ligands to study docking studies. Withanolide A and Cyclosporines had shown good inhibition activity against Cyclophilin A, whereas Columbin, Boswellic acid, Cucurbitacin E, Vitamin E and N-Acetyl cysteine ( NAC HGNC) had shown inhibitory activity against TRMP2. Thus, we suggest conducting further studies to conclude above pathways mechanism and inhibitory effect of natural compounds against the Nsp1 HGNC/ Nsp3 HGNC mediated pathways Invitro and In vivo.

    SARS-CoV-2 protein Nsp1 HGNC alters actomyosin cytoskeleton and phenocopies arrhythmogenic cardiomyopathy-related PKP2 HGNC mutant

    Authors: Cristina Marquez-Lopez; Marta Roche-Molina; Nieves García-Quintáns; Silvia Sacristan; David Siniscalco; Andrés Gonzalez-Guerra; Emilio Camafeita; Mariya Lytvyn; María Isabel Guillén; David Sanz-Rosa; Daniel Martín-Pérez; Cristina Sanchez-Ramos; Ricardo Garcia; Juan Antonio Bernal; 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:10.1101/2020.09.14.296178 Date: 2020-09-16 Source: bioRxiv

    Mutations in desmosomal Plakophilin-2 HGNC ( PKP2 HGNC) are the most prevalent drivers of arrhythmogenic-cardiomyopathy MESHD ( ACM MESHD) and a common cause of sudden death MESHD in young athletes. However, partner proteins that elucidate PKP2 HGNC cellular mechanism behind cardiac dysfunction MESHD in ACM MESHD are mostly unknown. Here we identify the actin-based motor proteins Myh9 HGNC and Myh10 HGNC as key PKP2 HGNC interactors and demonstrate that expression of the ACM MESHD-related PKP2 HGNC mutant R735X alters actin fiber organization and cell mechanical stiffness. We also show that SARS-CoV-2 Nsp1 HGNC protein acts similarly to this known pathogenic R735X mutant, altering the actomyosin component distribution on cardiac cells. Our data reveal that Nsp1 HGNC hijacks PKP2 HGNC into the cytoplasm and mimics the effect of delocalized R735X mutant. These results demonstrate that cytoplasmic PKP2 HGNC drives actomyosin deregulation and structural collapse, validating a critical role of PKP2 HGNC localization in the regulation of actomyosin architecture. The fact that Nsp1 HGNC and R735X share similar phenotypes also suggests that direct SARS-CoV-2 heart infection MESHD could induce a transient ACM MESHD-like disease in COVID-19 MESHD patients, which may contribute to right ventricle dysfunction, observed in patients with poor prognosis.

    Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1

    Authors: Francesca Benedetti; Greg Snyder; Marta Giovanetti; Silvia Angeletti; Robert C. Gallo; Massimo Ciccozzi; Davide Zella

    doi:10.21203/ Date: 2020-08-19 Source: ResearchSquare

    Background:The new Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2), which was first detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic.Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome MESHD, MERS-CoV MESHD. Its genome is ∼30 kb in length and contains two large overlapping polyproteins, ORF1a PROTEIN and ORF1ab PROTEIN that encode for several structural and non-structural proteins. The non-structural protein 1 PROTEIN ( nsp1 HGNC) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by i) the presence of specific amino acid residues of nsp1 HGNC and b) the interaction between the protein and the host’s small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects.Methods: A total of 17928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 HGNC genomic regions were identified using BioEdit and verified using BLAST. Nsp1 HGNC protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER.Results: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure.Conclusions: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 HGNC suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host’s gene expression. In addition, substitution of the two amino acids (KS) from nsp1 HGNC of SARS-CoV MESHD was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 HGNC protein, both in the population of asymptomatic and pauci-symptomatic subjects, and ii) correlate these changes in nsp1 HGNC with potential decreased viral pathogenicity.

    Integrative Vectors for Regulated Expression of SARS-CoV-2 Proteins Implicated in RNA Metabolism

    Authors: Stefan Bresson; Nic Robertson; Emanuela Sani; Tomasz W Turowski; Vadim Shchepachev; Michaela Kompauerova; Christos Spanos; Aleksandra Helwak; David Tollervey

    doi:10.1101/2020.07.20.211623 Date: 2020-07-21 Source: bioRxiv

    Infection with SARS-CoV-2 is expected to result in substantial reorganization of host cell RNA metabolism. We identified 14 proteins that were predicted to interact with host RNAs MESHD or RNA binding proteins, based on published data for SARS-CoV and SARS-CoV-2 MESHD. Here, we describe a series of affinity-tagged and codon-optimized expression constructs for each of these 14 proteins. Each viral gene was separately tagged at the N-terminus with Flag-His8, the C-terminus with His8-Flag, or left untagged. The resulting constructs were stably integrated into the HEK293 Flp-In TREx genome. Each viral gene was expressed under the control of an inducible Tet-On promoter, allowing expression levels to be tuned to match physiological conditions during infection. Expression time courses were successfully generated for most of the fusion proteins and quantified by western blot. A few fusion proteins were poorly expressed, whereas others, including Nsp1 HGNC, Nsp12, and N protein PROTEIN, were toxic unless care was taken to minimize background expression. All plasmids can be obtained from Addgene and cell lines are available. We anticipate that availability of these resources will facilitate a more detailed understanding of coronavirus molecular biology.

    SARS-CoV-2 Nsp1 HGNC binds ribosomal mRNA channel to inhibit translation

    Authors: Katharina Schubert; Evangelos D. Karousis; Ahmad Jomaa; Alain Scaiola; Blanca Echeverria; Lukas-Adrian Gurzeler; Marc Leibundgut; Volker Thiel; Oliver Muehlemann; Nenad Ban

    doi:10.1101/2020.07.07.191676 Date: 2020-07-07 Source: bioRxiv

    The non-structural protein 1 PROTEIN ( Nsp1 HGNC), also referred to as the host shutoff factor PROTEIN, is the first viral protein that is synthesized in SARS-CoV-2 infected MESHD human cells to suppress host innate immune functions1,2. By combining cryo-electron microscopy and biochemical experiments, we show that SARS-CoV-2 Nsp1 HGNC binds to the human 40S subunit in ribosomal complexes including the 43S pre-initiation complex. The protein inserts its C-terminal domain at the entrance to the mRNA channel where it interferes with mRNA binding. We observe potent translation inhibition in the presence of Nsp1 HGNC in lysates from human cells. Based on the high-resolution structure of the 40S- Nsp1 HGNC complex, we identify residues of Nsp1 HGNC crucial for mediating translation inhibition. We further show that the full-length 5’ untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines inhibition of translation by Nsp1 HGNC with efficient translation of the viral mRNA to achieve expression of viral genes3.Competing Interest StatementThe authors have declared no competing interest.View Full Text

    Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2

    Authors: Vipin Gupta; Shazia Haider; Mansi Verma; Kalaiarasan Ponnusamy; Md. Zubbair Malik; Nirjara Singhvi; Helianthous Verma; Roshan Kumar; Utkarsh Sood; Princy Hira; Shiva Satija; Rup Lal

    doi:10.1101/2020.06.20.162560 Date: 2020-06-20 Source: bioRxiv

    SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome MESHD resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 MESHD COVID-19 MESHD pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3 HGNC, ORF8 PROTEIN, Nsp13, S, Nsp12, Nsp2 HGNC and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 HGNC was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins PROTEIN with ACE2 HGNC, but it also showed better interaction with TMPRSS2 HGNC receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A HGNC, MYO5B HGNC & MYO5C HGNC had maximum interaction with viral hub proteins (Nucleocapsid PROTEIN, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 HGNC proteins which could be an effective target for COVID-19 MESHD treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia MESHD and thrombotic MESHD conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 HGNC and N proteins PROTEIN which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.

    Structural basis for translational shutdown and immune evasion by the Nsp1 HGNC protein of SARS-CoV-2

    Authors: Matthias Thoms; Robert Buschauer; Michael Ameismeier; Lennart Koepke; Timo Denk; Maximilian Hirschenberger; Hanna Kratzat; Manuel Hayn; Timur Mackens-Kiani; Jingdong Cheng; Christina Martina Stuerzel; Thomas Froehlich; Otto Berninghausen; Thomas Becker; Frank Kirchhoff; Konstantin Maria Johannes Sparrer; Roland Beckmann

    doi:10.1101/2020.05.18.102467 Date: 2020-05-18 Source: bioRxiv

    SARS-CoV-2 is the causative agent of the current COVID-19 pandemic MESHD COVID-19 pandemic MESHD. A major virulence factor of SARS-CoVs MESHD is the nonstructural protein 1 ( Nsp1 HGNC) which suppresses host gene expression by ribosome association via an unknown mechanism. Here, we show that Nsp1 HGNC from SARS-CoV-2 binds to 40S and 80S ribosomes, resulting in shutdown of capped mRNA translation both in vitro and in cells. Structural analysis by cryo-electron microscopy (cryo-EM) of in vitro reconstituted Nsp1 HGNC-40S and of native human Nsp1 HGNC-ribosome complexes revealed that the Nsp1 HGNC C-terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 HGNC effectively blocks RIG-I HGNC-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 HGNC may aid structure-based drug design against SARS-CoV-2.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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