Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (547)

ProteinS (185)

ComplexRdRp (33)

ProteinE (33)

ORF1ab (27)


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SARS-CoV-2 Proteins
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    A Study on Non-Synonymous Mutational Patterns in Structural Proteins of SARS-COV-2

    Authors: Jayanta Das; Swarup Roy

    id:10.20944/preprints202008.0621.v2 Date: 2021-03-04 Source: Preprints.org

    SARS-CoV-2 is mutating and creating divergent variants across the world. An in-depth investigation of the amino acid substitution in the genomic signature of SARS-CoV-2 proteins is highly essential for understanding its host adaptation and infection biology. A total of 9587 SARS-CoV-2 structural protein sequences collected from 49 different countries are used to characterize protein-wise variants, substitution pattern (type and location), and major substitution changes. The majority of the substitutions are distinct, occurred mostly in a particular location, and leads to a change in amino acid's biochemical properties. In terms of mutational changes, Envelope (E) and Membrane ( M) proteins PROTEIN are relatively stable than Nucleocapsid (N PROTEIN) and Spike (S) proteins PROTEIN. Several co-occurrence substitutions are observed, particularly in S and N proteins PROTEIN. Substitution specific to active sub-domains reveals that Heptapeptide Repeat, Fusion peptides, Transmembrane in S protein PROTEIN, and N-terminal and C-terminal domains in N protein PROTEIN are remarkably mutated, and also found few deleterious mutations in these domains.

    Inhibiting SARS-CoV-2 infection MESHD in vitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl-hydrocarbon receptor HGNC signal

    Authors: Keiji Tanimoto; Kiichi Hirota; Takahiro Fukazawa; Yoshiyuki Matsuo; Toshihito Nomura; Nazmul Tanuza; Nobuyuki Hirohashi; Hidemasa Bono; Takemasa Sakakuchi

    doi:10.1101/2021.03.04.433658 Date: 2021-03-04 Source: bioRxiv

    Since understanding molecular mechanisms of SARS-CoV-2 infection MESHD is extremely important for developing effective therapies against COVID-19 MESHD, we focused on the internalization mechanism of SARS-CoV-2 via ACE2 HGNC. Although cigarette smoke is generally believed to be harmful to the pathogenesis of COVID-19 MESHD, cigarette smoke extract (CSE) treatments were surprisingly found to suppress the expression of ACE2 HGNC in HepG2 cells. We thus tried to clarify the mechanism of CSE effects on expression of ACE2 HGNC in mammalian cells. Because RNA-seq analysis suggested that suppressive effects on ACE2 HGNC might be inversely correlated with induction of the genes regulated by aryl hydrocarbon receptor HGNC ( AHR MESHD AHR HGNC), the AHR MESHD AHR HGNC agonists 6-formylindolo(3,2-b)carbazole (FICZ) and omeprazole ( OMP HGNC) were tested to assess whether those treatments affected ACE2 HGNC expression. Both FICZ and OMP HGNC clearly suppressed ACE2 HGNC expression in a dose-dependent manner along with inducing CYP1A1 HGNC. Knock-down experiments indicated a reduction of ACE2 HGNC by FICZ treatment in an AHR HGNC-dependent manner. Finally, treatments of AHR MESHD agonists inhibited SARS-CoV-2 infection MESHD into Vero E6 cells as determined with immunoblotting analyses detecting SARS-CoV-2 specific nucleocapsid protein PROTEIN. We here demonstrate that treatment with AHR HGNC AHR MESHD agonists, including CSE, FICZ, and OMP HGNC, decreases expression of ACE2 HGNC via AHR MESHD AHR HGNC activation, resulting in suppression of SARS-CoV-2 infection MESHD in mammalian cells.

    SARS-CoV-2 Sequence Characteristics of COVID-19 MESHD Persistence and Reinfection

    Authors: Manish Chandra Choudhary; Charles R Crain; Xueting Qiu; William Hanage; Jonathan Z. Li

    doi:10.1101/2021.03.02.21252750 Date: 2021-03-03 Source: medRxiv

    BackgroundBoth SARS-CoV-2 reinfection and persistent infection have been described, but a systematic assessment of mutations is needed. We assessed sequences from published cases of COVID-19 MESHD reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. MethodsA systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistent infection with available sequences. Amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent COVID-19 MESHD to community-driven evolution. ResultsFourteen reinfection and five persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 9 amino acid changes with enrichment of changes in the S, ORF8 PROTEIN and N genes PROTEIN. The number of amino acid changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 MESHD demonstrated more rapid accumulation of mutations than seen with community-driven evolution with continued viral changes during convalescent plasma or monoclonal antibody treatment. ConclusionsSARS-CoV-2 reinfection does not require an unusual set of circumstances in the host or virus, while persistent COVID-19 MESHD is largely described in immunosuppressed individuals and is associated with accelerated viral evolution as measured by clock rates.

    Introductions and evolutions of SARS-CoV-2 strains in Japan

    Authors: Reitaro Tokumasu; Dilhan Weeraratne; Jane Snowdon; Laxmi Parida; Michiharu Kudo; Takahiko Koyama

    doi:10.1101/2021.02.26.21252555 Date: 2021-03-02 Source: medRxiv

    COVID-19 MESHD caused by SARS-CoV-2 was first identified in Japan on January 15th, 2020, soon after the pandemic originated in Wuhan, China. Subsequently, Japan experienced three distinct waves of the outbreak in the span of a year and has been attributed to new exogenous strains and evolving existing strains. Japan engaged very early on in tracking different COVID-19 MESHD sub-strains and have sequenced approximately 5% of all confirmed cases. While Japan has enforced stringent airport surveillance on cross-border travelers and returnees, some carriers appear to have advanced through the quarantine stations undetected. In this study, 17112 genomes sampled in Japan were analyzed to understand the strains, heterogeneity and temporal evolution of different SARS-CoV-2 strains. We identified 11 discrete strains with a substantial number of cases with most strains possessing the spike (S) D614G and nucleocapsid (N PROTEIN) 203_204delinsKR mutations. Besides these variants, ORF1ab PROTEIN P3371S, A4815V, S1361P, and N P151L were also detected in nearly half the samples constituting the most common strain in Japan. 115 distinct strains have been introduced into Japan and 12 of them were introduced after strict quarantine policy was implemented. In particular, the B.1.1.7 strain, that emerged in the United Kingdom (UK) in September 2020, has been circulating in Japan since late 2020 after eluding cross-border quarantine stations. Similarly, the B.1.351 strain dubbed the South African variant, P.1 Brazilian strain and R.1 strain with the spike E484K mutation have been detected in Japan. At least four exogenous B.1.1.7 sub-strains have been independently introduced in Japan as of late January 2021, and these strains carry mutations that give selective advantage including N501Y, H69_V70del, and E484K that confer increased transmissibility, reduced efficacy to vaccines and possible increased virulence. It is imperative that the quarantine policy be revised, cross-border surveillance reinforced, and new public health measures implemented to mitigate further transmission of this deadly disease and to identify strains that may engender resistance to vaccines.

    High Initial Titres of Anti-Spike Antibodies following SARS-CoV-2 Infection MESHD is Associated with Faster Decay Rates at Four Months Follow-Up

    Authors: VIDYA MENON; Masood A Shariff; Victor Perez Gutierrez; Juan M Carreno; Bo Yu; Muzamil Jawed; Marcia Gossai; Elisenda Valdez; Anjana A Pillai; Usha Venugopal; Moiz Kasubhai; Vihren Dimitrov; Florian Krammer

    doi:10.1101/2021.03.02.21252362 Date: 2021-03-02 Source: medRxiv

    Background Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggests an initial decay of antibody followed by subsequent stabilization. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein PROTEIN and spike (S) protein PROTEIN and to evaluate their correlation to clinical symptoms among healthcare workers (HCW). Methods In this cross-sectional longitudinal cohort study done in two phases over four months, HCW underwent serial qualitative serology testing for anti-N antibody, quantitative MSH-ELISA to detect Receptor Binding Domain and full-length S reactive antibodies and completed online surveys about COVID-19 MESHD related symptoms and healthcare/community exposure. Results Anti-N antibody positivity was 27% and anti-S positivity was 28% in Phase 1. In Phase 2 anti-S titres were higher in symptomatic than in asymptomatic positive subjects in Phase 1. Marginally higher titers were seen in asymptomatic compared to the symptomatic positive subgroup in Phase 2. A positive correlation was noted between age, number and duration of symptoms, and Phase 1 anti-S antibody titre. A strong correlation was observed between Phase 1 titers and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever MESHD, GI symptoms MESHD, and total number and duration of COVID-19 MESHD symptoms. Conclusions Higher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as faster decay during the two time points.

    Seroprevalence of Human Coronaviruses Among Patients Visiting Hospital-Based Sentinel Sites in Uganda

    Authors: MULABBI NICHOLAS ELIJAH; Robert Tweyongyere; Fred Wabwire-Mangen; Edison Mworozi; Jeff Koehlerb; Hannah Kibuuka; Monica Millard; Bernard Erima; Titus Tugume; Ukuli Qouilazoni Aquino; Denis K. Byarugaba

    doi:10.21203/rs.3.rs-291307/v1 Date: 2021-03-02 Source: ResearchSquare

    Background: Human coronaviruses are causative agents of respiratory infections MESHD with several subtypes being prevalent worldwide. They cause respiratory illnesses of varying severity and have been described to be continuously emerging but their prevalence is not well documented in Uganda. This study assessed the seroprevalence of antibodies against the previously known human coronaviruses prior 2019 in Uganda.Methods: A total 377 serum samples collected from volunteers that showed influenza like illness in five hospital-based sentinel sites and archived were analyzed using a commercial Qualitative Human Coronavirus Antibody IgG ELISA kit. Although there is no single kit available that can detect the presence of all the circulating coronaviruses, this kit uses a nucleoprotein PROTEIN, aa 340-390 to coat the wells and since there is significant homology among the various human coronavirus strains with regards to the coded for proteins, there is significant cross reactivity beyond HCoV HKU-39849 2003. This gives the kit a qualitative ability to detect the presence of human coronavirus antibodies in a sample. Results: The overall seroprevalence for all the sites was 87.53% with no significant difference in the seroprevalence between the Hospital based sentinel sites (p=0.8). Of the seropositive, the age group 1-5 years had the highest percentage (46.97), followed by 6-10 years (16.67) and then above 20 (16.36). The volunteers were divided into two broad categories, those below five years and those above five years, to calculate the odds ratio. The odds ratio of those seropositive with an age above 5 years with reference to those below 5 years was 0.62. This shows that those below 5 are more likely to be seropositive compared to those above 5 years. The seropositivity was generally high throughout the year with highest being recorded in March and the lowest in February and December. Conclusions: The seroprevalence of Human coronaviruses is alarmingly high which calls for need to identify and characterize the circulating coronavirus strains so as to guide policy on the control strategies.

    SARS-CoV-2 Total and Subgenomic RNA Viral Load in Hospitalized Patients

    Authors: Derek E. Dimcheff; Andrew L. Valesano; Kalee E. Rumfelt; William J. Fitzsimmons; Christopher Blair; Carmen Mirabelli; Joshua G. Petrie; Emily T. Martin; Chandan Bhambhani; Muneesh Tewari; Adam S. Lauring

    doi:10.1101/2021.02.25.21252493 Date: 2021-03-01 Source: medRxiv

    Understanding viral load in patients infected with SARS-CoV-2 is critical to epidemiology and infection control. Previous studies have demonstrated that SARS-CoV-2 RNA can be detected for many weeks after symptom onset. The clinical significance of this finding is unclear and, in most patients, likely does not represent active infection. There are, however, patients who shed infectious virus for weeks. Detection of subgenomic RNA transcripts expressed by SARS-CoV-2 has been proposed to represent productive infection and may be a tractable marker for monitoring infectivity. Here, we use RT-PCR to quantify total and subgenomic nucleocapsid (N PROTEIN) and envelope (E) transcripts in 190 SARS-CoV-2 positive samples collected on hospital admission. We relate these findings to duration of symptoms. We find that all transcripts decline at the same rate; however, subgenomic E becomes undetectable before other transcripts. In Kaplan-Meier analysis the median duration of symptoms to a negative test is 14 days for sgE and 25 days for sgN. There is a linear decline in subgenomic RNA compared to total RNA suggesting subgenomic transcript copy number is highly dependent on copy number of total transcripts. The mean difference between total N and subgenomic N is 16-fold (4.0 cycles) and the mean difference between total E and sub-genomic E is 137-fold (7.1 cycles). This relationship is constant over duration of symptoms allowing prediction of subgenomic copy number from total copy number. Although Subgenomic E is undetectable at a time that may more closely reflect the duration of infectivity, its utility in determining active infection may be no more useful than a copy number threshold determined for total transcripts.

    Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target

    Authors: Takeshi Yamamotoya; Yusuke Nakatsu; Shun Hasei; Yukino Ohata; Jeffrey Encinas; Hisanaka Ito; Takayoshi Okabe; Tomoichiro Asano; Takemasa Sakaguchi

    doi:10.21203/rs.3.rs-284607/v1 Date: 2021-02-28 Source: ResearchSquare

    Novel coronavirus disease 2019 MESHD ( COVID-19 MESHD) has emerged as a global pandemic with far-reaching societal impact. Here we demonstrate that Pin1 is a key cellular molecule necessary for severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) propagation. In this study, siRNA-mediated silencing of Pin1 expression markedly suppressed the proliferation of SARS-CoV-2 in VeroE6/TMPRSS2 cells. In addition, several recently generated Pin1 inhibitors showed strong inhibitory effects on SARS-CoV-2 proliferation, measured by both viral mRNA and protein synthesis, and alleviated the cytopathic effect (CPE) on VeroE6/TMPRSS2 cells. One compound, termed H-77, was found to block SARS-CoV-2 proliferation at an EC50 below 5 µM regardless of whether it was added to the culture medium prior to or after SARS-CoV-2 infection MESHD. The inhibition of viral N protein PROTEIN mRNA synthesis by H-77 implies that the molecular mechanism underlying SARS-CoV-2 inhibition is likely to be associated with viral gene transcription or earlier steps. Another Pin1 inhibitor, all-trans retinoic acid (ATRA)—a commercially available drug used to treat acute promyelocytic leukemia MESHD ( APL MESHD) and which both activates the retinoic acid receptor and inhibits the activity of Pin1—similarly reduced the proliferation of SARS-CoV-2. Taken together, the results indicate that Pin1 inhibitors could serve as potential therapeutic agents for COVID-19 MESHD.

    Clinical evaluation of a multiplex RT-PCR assay for detection of SARS-CoV-2 in individual and pooled upper respiratory tract samples

    Authors: Melissa Laverack; Rebecca L. Tallmadge; Roopa Venugopalan; Brittany Cronk; XiuLin Zhang; Rolf Rauh; Amy Saunders; William M. Nelson; Elizabeth Plocharczyk; Diego G. Diel

    doi:10.21203/rs.3.rs-280275/v1 Date: 2021-02-27 Source: ResearchSquare

    The aim of this study was to identify and validate a sensitive, high-throughput and cost-effective SARS-CoV-2 RT-PCR assay to be used as a surveillance and diagnostic tool for SARS-CoV-2 in a University surveillance program. We conducted a side-by-side clinical evaluation of a newly developed SARS-CoV-2 multiplex assay (EZ-SARS-CoV-2 Real-Time RT-PCR) with the commercial TaqPath COVID-19 MESHD Combo kit, which has an Emergency Use Authorization from the FDA. The EZ-SARS-CoV-2 RT-PCR incorporates two assays targeting the SARS-CoV-2 N gene PROTEIN, an internal control targeting the human RNase P gene, and a PCR inhibition control in a single reaction. Nasopharyngeal (NP) and anterior nares (AN) swabs were tested as individuals and pools with both assays and in the ABI 7500 Fast and the QuantStudio 5 detection platforms. The EZ-SARS-CoV-2 RT-PCR assay analytical sensitivity was 250 copies/ml or approximately 1.75 genome copy equivalents per reaction. Clinical performance of the EZ-SARS-CoV-2 assay was determined using NP and AN samples tested in other laboratories. The diagnostic sensitivity of the assay ranged between 94 and 96% across the detection platforms, and the diagnostic specificity was 94.06%. The positive predictive value was 94% and the negative predictive value ranged from 94 to 96%. Pooling five NP or AN specimens yielded 93% diagnostic sensitivity. The overall agreement between these SARS-CoV-2 RT-PCR assays was high, supported by Cohen’s kappa value of 0.93. The EZ-SARS-CoV-2 RT-PCR assay performance attributes of high sensitivity, excellent performance in AN sample matrix and in pooled upper respiratory samples support its use in a high-throughput surveillance testing program.

    Longitudinal analysis of SARS-CoV-2 seroprevalence using multiple serology platforms

    Authors: Juan Manuel Carreno; Damodara Rao Mendu; Viviana Simon; Masood A Shariff; Gagandeep Singh; Vidya Menon; Florian Krammer

    doi:10.1101/2021.02.24.21252340 Date: 2021-02-26 Source: medRxiv

    Serological tests are important tools helping to determine previous infection with severe acute respiratory disease coronavirus MESHD 2 (SARS-CoV-2) and to monitor immune responses. The current tests are based on spike (S), the receptor binding domain (RBD), or the nucleoprotein PROTEIN (NP) as substrate. Here, we used samples from a high seroprevalence cohort of health care workers (HCWs) to perform a longitudinal analysis of the antibody responses using three distinct serological assays. 501 serum samples were tested using: a) a research-grade RBD and spike based tandem enzyme-linked immunosorbent assay (MS-RBD ELISA, MS-spike ELISA), b) a commercial RBD and spike based tandem ELISA (Kantaro-RBD, -spike), and c) a commercial NP-based chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). Seroprevalence ranged around 28% during the early stage of the pandemic (a: 28.4% positives; b: 28.1%; c: 27.3%). Good correlation was observed between the MS MESHD and Kantaro RBD ELISAs and between the MS MESHD and Kantaro spike ELISAs. By contrast, modest correlations were observed between the Abbott Architect and both RBD and spike-based assays. A proportion of HCWs (n=178) were sampled again 3-5 months after the first time point. Although antibody levels declined in most of the positive individuals, the overall seroprevalence measured by RBD-spike based assays remained unchanged. However the seroprevalence of NP-reactive antibodies significantly declined. Lastly, we tested six samples of individuals who received two doses of SARS-CoV-2 mRNA vaccine and found that seroconversion was detected by the RBD-spike assays but, of course as expected, not the NP based assay. In summary, our results consolidate the strength of different serological assays to assess the magnitude and duration of antibodies to SARS-CoV-2.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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