Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ComplexRdRp (26)

ProteinN (26)

ProteinS (7)

ProteinE (5)

ORF1ab (5)


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SARS-CoV-2 Proteins
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    Diagnostic Performance of Pooled RT-PCR Testing for SARS-CoV-2 Detection

    Authors: Diadem Ricarte; Aubrey Gador; Leomill Mendiola; Ian Christian Gonzales

    doi:10.1101/2021.02.17.21251961 Date: 2021-02-19 Source: medRxiv

    BackgroundWith the high number of COVID-19 MESHD cases, a need to optimize testing strategy must be regarded to obtain timely diagnosis for early containment measures. With this, several studies have employed pooled RT-PCR testing for SARS-CoV-2 as this could potentially conserve laboratory resources while has the capacity to test several individuals. However, this was recommended to firstly validate the method as different laboratory reagents and equipment vary with its diagnostic performance. ObjectiveThe aim of this study was to determine the diagnostic performance of pooled SARS-CoV-2 nasopharyngeal/oropharyngeal swabbed samples using RT-PCR technique. MethodsA records review of two-staged pooled RT-PCR testing data from August 10, 26, 30 and September 5, 2020 was utilized from Northern Mindanao Medical Center COVID-19 MESHD Satellite Laboratory (formerly CHDNM TB Regional Center). For the first stage, using known samples, a total of 30 pools were made for each of the pooling size, 5- and 10-pooled, on both pooling phase, pre- and post-RNA extraction. One positive individual was used to represent each of the Cycle threshold values given (<24, 25-28, 29-32, 33-36, and 37-40) while the rest of the samples were negative. For the second stage, 54 pools of five from 270 random unknown samples were used to validate the results. Target gene performance of N gene PROTEIN and RdRp PROTEIN was also determined. Key ResultsResults show that 5-pooled sample has higher sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of 100% (95% confidence interval (CI) 88.97-100), 66.95% (95% CI, 60.75-72.6), 28.18% (95% CI, 20.62-37.22), and 100% (95% CI, 97.66-100) compared to 10-pooled sample that has 87.1% (95% CI, 71.15-94.87), 56.9% (50.57-63.02), 20.77% (95% CI, 14.68-28.53) and 97.14% (95% CI, 92.88-98.88). Further, these Ct values were only from the N gene PROTEIN, emphasizing its higher diagnostic performance as well to detect SARS-CoV-2 compared to RdRp PROTEIN as only a few samples were detected, thus, no analysis was made. ConclusionThis study found out that 5-pooled sample has better diagnostic performance compared to 10-pooled samples. Specifically, all positive individual samples were detected in 5-pooled samples in pre-RNA extraction phase which these results are evident and consistent on both known and unknown samples. N gene PROTEIN was found out to detect more SARS-CoV-2 samples compared to RdRp PROTEIN.

    Comparative analysis of loop-mediated isothermal amplification (LAMP)-based assays for rapid detection of SARS-CoV-2 genes

    Authors: Daniel Urrutia-Cabrera; Roxanne Hsiang-Chi Liou; Jianxiong Chan; Sandy Shen-Chi Hung; Alex W Hewitt; Keith Martin; Patrick Kwan; Raymond Ching-Bong Wong

    doi:10.1101/2020.12.21.20248288 Date: 2020-12-22 Source: medRxiv

    The COVID-19 pandemic MESHD caused by SARS-CoV-2 has infected millions worldwide and there is an urgent need to increase our diagnostic capacity to identify infected cases. Although RT-qPCR remains the gold standard for SARS-CoV-2 detection, this method requires specialised equipment in a diagnostic laboratory and has a long turn-around time to process the samples. To address this, several groups have recently reported development of loop-mediated isothermal amplification (LAMP) as a simple, low cost and rapid method for SARS-CoV-2 detection. Herein we present a comparative analysis of three LAMP-based assays that target different regions of the SARS-CoV-2: ORF1ab PROTEIN RdRP PROTEIN, ORF1ab PROTEIN nsp3 HGNC and Gene N PROTEIN. We perform a detailed assessment of their sensitivity, kinetics and false positive rates for SARS-CoV-2 diagnostics in LAMP or RT-LAMP reactions, using colorimetric or fluorescent detection. Our results independently validate that all three assays can detect SARS-CoV-2 in 30 minutes, with robust accuracy at detecting as little as 1000 RNA copies and the results can be visualised simply by color changes. We also note the shortcomings of these LAMP-based assays, including variable results with shorter reaction time or lower load of SARS-CoV-2, and false positive results in some experimental conditions. Overall for RT-LAMP detection, the ORF1ab PROTEIN RdRP PROTEIN and ORF1ab PROTEIN nsp3 HGNC assays have higher sensitivity and faster kinetics for detection, whereas the Gene N PROTEIN assay exhibits no false positives in 30 minutes reaction time. This study provides validation of the performance of LAMP-based assays for SARS-CoV-2 detection, which have important implications in development of point-of-care diagnostic for SARS-CoV-2.

    Antibody landscape against SARS-CoV-2 proteome revealed significant differences between non-structural/ accessory proteins and structural proteins

    Authors: Yang Li; Zhaowei Xu; Qing Lei; Danyun Lai; Hongyan Hou; Hewei Jiang; yunxiao Zheng; Xuening Wang; Jiaoxiang Wu; Mingliang Ma; Bo Zhang; Hong Chen; Caizheng Yu; Junbiao Xue; Nainang Zhang; Huan Qi; Shujuan Guo; Yandi Zhang; Xiaosong Lin; Zongjie Yao; Huiming Sheng; Ziyong Sun; Feng Wang; Xionglin Fan; Sheng-ce Tao

    doi:10.1101/2020.12.08.20246314 Date: 2020-12-11 Source: medRxiv

    The immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 MESHD sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1 HGNC, NSP7 PROTEIN, NSP8 PROTEIN, RdRp PROTEIN, ORF3b PROTEIN and ORF9b PROTEIN elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein PROTEIN. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N HGNC N protein PROTEIN before death was observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology. HighlightsO_LIAn antibody response landscape against SARS-CoV-2 proteome was constructed C_LIO_LINon-structural/accessory proteins elicit prevalent antibody responses but likely through a different mechanism to that of structural proteins C_LIO_LIIgG antibodies against non-structural/accessory proteins are more associated with disease severity and clinical outcome C_LIO_LIFor non-survivors, the levels of IgG antibodies against S1 and N HGNC decline significantly before death C_LI

    Temporal patterns in the evolutionary genetic distance of SARS-CoV-2 during the COVID-19 MESHD COVID-19 MESHD pandemic

    Authors: Jingzhi Lou; Shi Zhao; Lirong Cao; Zigui Chen; Renee WY Chan; Marc KC Chong; Benny CY Zee; Paul KS Chan; Maggie H Wang; Marian J Killip; Patricia A Cane; Christine B Bruce; Allen D.G Roberts; Guanghui Tian; Haji A. Aisa; Tianwen Hu; Daibao Wei; Yi Jiang; Gengfu Xiao; Hualiang Jiang; Leike Zhang; Xuekui Yu; Jingshan Shen; Shuyang Zhang; H. Eric Xu

    doi:10.1101/2020.11.01.363739 Date: 2020-11-02 Source: bioRxiv

    Background: During the pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD), the genetic mutations occurred in severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) cumulatively or sporadically. In this study, we employed a computational approach to identify and trace the emerging patterns of the SARS-CoV-2 mutations, and quantify accumulative genetic distance across different periods and proteins. Methods: Full-length human SARS-CoV-2 strains in United Kingdom were collected. We investigated the temporal variation in the evolutionary genetic distance defined by the Hamming distance since the start of COVID-19 pandemic MESHD. Findings: Our results showed that the SARS-CoV-2 was in the process of continuous evolution, mainly involved in spike protein (S PROTEIN S protein HGNC), the RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) region of open reading frame 1 PROTEIN ( ORF1 PROTEIN) and nucleocapsid protein (N PROTEIN protein). By contrast, mutations in other proteins were sporadic and genetic distance to the initial sequenced strain did not show an increasing trend.

    Drug Design and Repurposing with DockThor-VS Web Server: Virtual Screening focusing on SARS-CoV-2 Therapeutic Targets and their Non-Synonym Variants

    Authors: Isabella A. Guedes; Leon S. C. Costa; Karina B. dos Santos; Ana L. M. Karl; Gregório K. Rocha; Iury M. Teixeira; Marcelo M. Galheigo; Vivian Medeiros; Eduardo Krempser; Fábio L. Custódio; Helio J. C. Barbosa; Marisa F. Nicolás; Laurent E. Dardenne

    doi:10.21203/rs.3.rs-96789/v1 Date: 2020-10-22 Source: ResearchSquare

    The COVID-19 MESHD caused by the SARS-CoV-2 virus was declared as a pandemic disease in March 2020 by the World Health Organization (WHO). Structure-Based Drug Design strategies based on docking methodologies have been widely used for both new drug development and drug repurposing to find effective treatments against this disease. In this work, we present the developments implemented in the DockThor-VS web server to provide a virtual screening (VS) platform with curated structures of potential therapeutic targets from SARS-CoV-2 incorporating genetic information regarding relevant non-synonymous variations. The web server facilitates repurposing VS experiments providing curated libraries of currently available drugs on the market. Currently, DockThor-VS provides ready-for-docking 3D structures for wild type and selected mutations for Nsp3 HGNC (papain-like, PLpro PROTEIN domain), Nsp5 HGNC ( Mpro PROTEIN, 3CLpro PROTEIN), Nsp12 ( RdRp PROTEIN), Nsp15 (NendoU), N protein PROTEIN and Spike. We performed VS experiments of FDA-approved drugs considering the therapeutic targets available at the web server to assess the impact of considering different structures and mutations in the identification of possible new treatments of SARS-CoV-2 infections MESHD. The DockThor-VS is freely available at www.dockthor.lncc.br.

    One-tube SARS-CoV-2 detection platform based on RT-RPA and CRISPR/Cas12a

    Authors: Yangyang Sun; Lei Yu; Chengxi Liu; Shanting Ye; Wei Chen; Dechang Li; Weiren Huang

    doi:10.21203/rs.3.rs-96229/v2 Date: 2020-10-21 Source: ResearchSquare

    Background: COVID-19 MESHD has spread rapidly around the world, affecting a large percentage of the population. When lifting certain mandatory measures for an economic restart, robust surveillance must be established and implemented, with nucleic acid detection for SARS-CoV-2 as an essential component. Methods: We tried to develop a one-tube detection platform based on RT-RPA (Reverse Transcription and Recombinase Polymerase Isothermal Amplification) and DNA Endonuclease PROTEIN-Targeted CRISPR Trans Reporter (DETECTR) technology, termed OR-DETECTR, to detect SARS-CoV-2. We designed RT-RPA primers of the RdRp PROTEIN and N genes PROTEIN following the SARS-CoV-2 gene sequence. We optimized reaction components so that the detection process could be carried out in one tube. Specificity was demonstrated by detecting nucleic acid samples from pseudoviruses from seven human coronaviruses and Influenza A (H1N1). Clinical samples were used to validate the platform and all results were compared to rRT-PCR. RNA standards and pseudoviruses diluted by different gradients were used to demonstrate the detection limit. Additionally, we have developed a lateral flow assay based on OR-DETECTR for detecting COVID-19 MESHD.Results: The OR-DETECTR detection process can be completed in one tube, which takes approximately 50 min. This method can specifically detect SARS-CoV-2 from seven human coronaviruses and Influenza A (H1N1), with a low detection limit of 2.5 copies/µl input (RNA standard) and 1 copy/µl input (pseudovirus). Results of six samples from SARS-CoV-2 patients, eight samples from patients with fever MESHD but no SARS-CoV-2 infection MESHD, and one mixed sample from 40 negative controls showed that OR-DETECTR is 100% consistent with rRT-PCR. The lateral flow assay based on OR-DETECTR can be used for the detection of COVID-19 MESHD, and the detection limit is 2.5 copies/µl input.Conclusions: The OR-DETECTR platform for the detection of COVID-19 MESHD is rapid, accurate, tube closed, easy-to-operate, and free of large instruments.

    Understanding the phase separation characteristics of nucleocapsid protein PROTEIN provides a new therapeutic opportunity against SARS-CoV-2

    Authors: Dan Zhao; Weifan Xu; Xiaofan Zhang; Xiaoting Wang; Enming Yuan; Yuanpeng Xiong; Shenyang Wu; Shuya Li; Nian Wu; Tingzhong Tian; Xiaolong Feng; Hantao Shu; Peng Lang; Xiaokun Shen; Haitao Li; Pilong Li; Jianyang Zeng

    doi:10.1101/2020.10.09.332734 Date: 2020-10-12 Source: bioRxiv

    The ongoing coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic has raised an urgent need to develop effective therapeutics against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As a potential antiviral drug target, the nucleocapsid (N) protein PROTEIN of SARS-CoV-2 functions as a viral RNA chaperone and plays vital and multifunctional roles during the life cycle of coronavirus1-3. In this study, we discovered that the N protein PROTEIN of SARS-CoV-2 undergoes liquid-liquid phase separation ( LLPS MESHD) both in vitro and in vivo, which is further modulated by viral RNA. In addition, we found that, the core component of the RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) of SARS-CoV-2, nsp12, preferentially partitions into the N protein PROTEIN condensates. Moreover, we revealed that, two small molecules, i.e., CVL218 and PJ34, can be used to intervene the N protein PROTEIN driven phase separation and loosen the compact structures of the condensates of the N-RNA-nsp12 complex of SARS-CoV-2. The discovery of the LLPS-mediated interplay between N protein PROTEIN and nsp12 and the corresponding modulating compounds illuminates a feasible way to improve the accessibility of antiviral drugs (e.g., remdesivir) to their targets (e.g., nsp12/ RdRp PROTEIN), and thus may provide useful hints for further development of effective therapeutic strategies against SARS-CoV-2.

    Healthcare workers in elderly care: a source of silent SARS-CoV-2 transmission?

    Authors: Mirjam Jeanne Dorine Dautzenberg; Andrea Eikelenboom-Boskamp; Jacqueline Janssen; Miranda Drabbe; Ewoud de Jong; Eefke Weesendorp; Marion Koopmans; Andreas Voss

    doi:10.1101/2020.09.07.20178731 Date: 2020-09-09 Source: medRxiv

    Importance: Healthcare workers (HCWs), including those with mild symptoms, may be an important source of COVID-19 MESHD within elderly care. Objective: To gain insight into the spread of SARS-CoV-2 among HCWs working in elderly care settings. Design: Cross-sectional study among HCWs working in elderly care in the South-East of the Netherlands, testing for SARS-CoV-2, between March 31 and April 17, 2020. Setting: HCWs working in geriatric rehabilitation, somatic and psychogeriatric wards or small-scale living groups and district nursing, with a total of 5245 HCWs within 4 organisations. Participants: 621 HCWs with mild respiratory symptoms. Main Outcomes: Number of HCWs testing positive for SARS-CoV-2 in pharyngeal swabs, using real-time reverse-transcriptase PCR targeting the SARS-CoV-2 E-gene PROTEIN, N-gene PROTEIN, and RdRP PROTEIN. HCWs filled out a survey to collect information on symptoms and possible sources of infection. Results: 133/615 (21.6%) HCWs tested positive for SARS-CoV-2, ranging from 15.6 to 44.4% per elderly care organisation, and from 0 to 64.3% per separate location of the organizations, respectively. 74.6% of tested HCWs were nursing staff, 1.7% elderly care physicians, 20.3% other HCWs with patient contact and 3.4% HCWs without patient contact. In the univariate analysis, fever MESHD, runny or stuffy nose, anosmia MESHD, general malaise, myalgia MESHD, headache MESHD and ocular pain MESHD were associated with SARS-CoV-2 positivity, while gastro-intestinal symptoms and respiratory symptoms, other than runny or stuffy nose were not. Risk factors for SARS-CoV-2 positivity were contact with patients or colleagues with suspected or proven COVID-19 MESHD. Whole genome sequencing of 22 samples in 2 facilities strongly suggests spread within facilities. Conclusions and Relevance: We found a high SARS-CoV-2 prevalence among HCWs in nursing homes and district nursing, supporting the hypothesis of undetected spread within elderly care facilities. Structural testing of elderly care HCWs, including track and trace of contacts, should be performed to control this spread, even when only mild symptoms are present.

    Temporal landscape of mutation accumulation in SARS-CoV-2 genomes from Bangladesh: possible implications from the ongoing outbreak in Bangladesh

    Authors: Otun Saha; Rokaiya Nurani Shatadru; Nadira Naznin Rakhi; Israt Islam; Md. Shahadat Hossain; Md. Mizanur Rahaman; Leo C James; Madeline A Lancaster; Zhu Shu; Zhiming Yuan; Lei Tong; Han Xia; Jingzhe Pan; Natalie Garton; Manish Pareek; Michael Barer; Craig J Smith; Stuart M Allan; Michelle M. Lister; Hannah C. Howson-Wells; Edward C Holmes; Matthew W. Loose; Jonathan K. Ball; C. Patrick McClure; - The COVID-19 Genomics UK consortium study group; Shi Chen

    doi:10.1101/2020.08.20.259721 Date: 2020-08-21 Source: bioRxiv

    Along with intrinsic evolution, adaptation to selective pressure in new environments might have resulted in the circulatory SARS-CoV-2 strains in response to the geoenvironmental conditions of a country and the demographic profile of its population. Thus the analysis of genomic mutations of these circulatory strains may give an insight into the molecular basis of SARS-CoV-2 pathogenesis and evolution favoring the development of effective treatment and containment strategies. With this target, the current study traced the evolutionary route and mutational frequency of 198 Bangladesh originated SARS-CoV-2 genomic sequences available in the GISAID platform over a period of 13 weeks as of 14 July 2020. The analyses were performed using MEGA 7, Swiss Model Repository, Virus Pathogen Resource and Jalview visualization. Our analysis identified that majority of the circulating strains in the country belong to B and/or L type among cluster A to Z and strikingly differ from both the reference genome and the first sequenced genome from Bangladesh. Mutations in Nonspecific protein 2 ( NSP2 PROTEIN NSP2 HGNC), NSP3 PROTEIN NSP3 HGNC, RNA dependent RNA polymerase PROTEIN ( RdRp PROTEIN), Helicase HGNC, Spike, ORF3a PROTEIN, and Nucleocapsid (N) protein PROTEIN were common in the circulating strains with varying degrees and the most unique mutations(UM) were found in NSP3 HGNC NSP3 PROTEIN (UM-18). But no or limited changes were observed in NSP9 PROTEIN, NSP11 PROTEIN, E (Envelope), NSP7a, ORF 6, and ORF 7b suggesting the possible conserved functions of those proteins in SARS-CoV-2 propagation. However, along with D614G mutation, more than 20 different mutations in the Spike protein PROTEIN were detected basically in the S2 domain. Besides, mutations in SR-rich region of N protein PROTEIN and P323L in RDRP PROTEIN were also present. However, the mutation accumulation showed an association with sex and age of the COVID-19 MESHD positive cases. So, identification of these mutational accumulation patterns may greatly facilitate drug/ vaccine development deciphering the age and the sex dependent differential susceptibility to COVID-19 MESHD.

    Retesting Positive for SARS-CoV-2 RNA in Recovered COVID-19 MESHD Patients Reveals Low Levels of Non-Replicating Virus

    Authors: Flora Marzia Liotti; Giulia Menchinelli; Simona Marchetti; Rosalba Ricci; Brunella Posteraro; Francesco Landi; Maurizio Sanguinetti; Paola Cattani

    doi:10.21203/rs.3.rs-59323/v1 Date: 2020-08-14 Source: ResearchSquare

    Background: The follow-up of COVID-19 MESHD recovered patients is especially important to assess their infectivity and/or transmissibility statuses in order to maximize the COVID-19 MESHD management and containment. The aim of this study was to determine both total (genomic) and replicative (sub-genomic) SARS-CoV-2 RNA levels in nasal/oropharyngeal swab (NOS) samples from patients at follow-up times after COVID-19 MESHD recovering. Materials/methods: We tested 176 NOS samples of COVID-19 MESHD recovered patients who were followed up at the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from 21 April to 18 June 2020, according to our COVID-19 MESHD care protocol. The RT-PCR tests were performed using the Allplex™ 2019-nCoV and the Quanty COVID-19 MESHD assays (for total RNA detection and quantification, respectively) and an in-house assay (for replicative RNA detection).  Results: Of 176 NOS samples studied, 32 (18.2%) tested positive for total RNA, with CT values ranging from 29.3 to 38.8 for E, RdRP PROTEIN, and N genes PROTEIN (9 samples), 32.2 to 39.3 for RdRP PROTEIN and N genes PROTEIN (7 samples) or 35.8 to 39.8 for the N gene PROTEIN (16 samples). Consistently, viral loads ranged from 1.6 × 101 to 1.3 × 104 RNA copies/mL. Interestingly, we found replicative RNA in only one of 32 positive samples based on the presence of E-gene PROTEIN sub-genomic RNA (CT value of 39.1). The CT value (29.3) of E-gene PROTEIN genomic RNA in this sample was the lowest among the CT values of all 9 samples in which the E gene PROTEIN was detected. Testing samples obtained from the 32 patients at the time of COVID-19 MESHD diagnosis showed that the CT values ranged from 17.1 to 38.1 for E, RdRP PROTEIN, and N genes PROTEIN. Of note, the mean CT value of E-gene PROTEIN sub-genomic RNA (34.9) in these samples differed of 9.0 ± 2.8 from the mean CT value of E-gene PROTEIN genomic RNA (25.9). Finally, all but one of the 32 patients had positive serology results against SARS-CoV-2. Conclusions: Our findings show that at least a proportion of COVID-19 MESHD recovered patients were still positive for SARS-CoV-2 RNA, despite to a lower extent, and that only a minority of them was likely to have actively replicating virus in the upper respiratory tract.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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