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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF1ab (27)

ProteinN (27)

ProteinS (6)

ProteinE (5)

ComplexRdRp (5)


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    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.

    Increased infections, but not viral burden, with a new SARS-CoV-2 variant

    Authors: Ann Sarah Walker; Karina Doris Vihta; Owen Gethings; Emma Pritchard; Joel Jones; Thomas House; Iain Bell; John Bell; John Newton; Jeremy Farrar; Ian Diamond; Ruth Studley; Emma Rourke; Jodie Hay; Susan Hopkins; Derrick W Crook; Tim Peto; Philippa Matthews; David W Eyre; Nicole W Stoesser; Koen Pouwels; - the COVID-19 Infection Survey team

    doi:10.1101/2021.01.13.21249721 Date: 2021-01-15 Source: medRxiv

    BackgroundA new variant of SARS-CoV-2, B.1.1.7/VOC202012/01, was identified in the UK in December-2020. Direct estimates of its potential to enhance transmission are limited. MethodsNose and throat swabs from 28-September-2020 to 2-January-2021 in the UKs nationally representative surveillance study were tested by RT-PCR for three genes (N PROTEIN, S and ORF1ab PROTEIN). Those positive only on ORF1ab PROTEIN+N, S-gene target failures (SGTF), are compatible with B.1.1.7/VOC202012/01. We investigated cycle threshold (Ct) values (a proxy for viral load), percentage of positives, population positivity and growth rates in SGTF vs non-SGTF positives. Results15,166(0.98%) of 1,553,687 swabs were PCR-positive, 8,545(56%) with three genes detected and 3,531(23%) SGTF. SGTF comprised an increasing, and triple-gene positives a decreasing, percentage of infections from late-November in most UK regions/countries, e.g. from 15% to 38% to 81% over 1.5 months in London. SGTF Ct values correspondingly declined substantially to similar levels to triple-gene positives. Population-level SGTF positivity remained low (<0.25%) in all regions/countries until late-November, when marked increases with and without self-reported symptoms occurred in southern England (to 1.5-3%), despite stable rates of non-SGTF cases. SGTF positivity rates increased on average 6% more rapidly than rates of non-SGTF positives (95% CI 4-9%) supporting addition rather than replacement with B.1.1.7/VOC202012/01. Excess growth rates for SGTF vs non-SGTF positives were similar in those up to high school age (5% (1-8%)) and older individuals (6% (4-9%)). ConclusionsDirect population-representative estimates show that the B.1.1.7/VOC202012/01 SARS-CoV-2 variant leads to higher infection rates, but does not seem particularly adapted to any age group.

    Structure-function investigation of a new VUI-202012/01 SARS-CoV-2 variant

    Authors: Jasdeep Singh; Nasreen Z Ehtesham; Syed Asad Rahman; Yakob G. Tsegay; Daniel S. Abebe; Mesay G. Edo; Endalkachew H. Maru; Wuletaw C. Zewde; Lydia K. Naylor; Dejen F. Semane; Menayit T. Deresse; Bereket B. Tezera; Lovisa Skoglund; Jamil Yousef; Elisa Pin; Wanda Christ; Mikaela Olausson; My Hedhammar; Hanna Tegel; Sara Mangsbo; Mia Phillipson; Anna Manberg; Sophia Hober; Peter Nilsson; Charlotte Thalin; Samuel Bates; Chevaun Morrison-Smith; Benjamin Nicholson; Edmond Wong; Leena El-Mufti; Michael Kann; Anna Bolling; Brooke Fortin; Hayden Ventresca; Wen Zhou; Santiago Pardo; Megan Kwock; Aditi Hazra; Leo Cheng; Rushdy Ahmad; James A. Toombs; Rebecca Larson; Haley Pleskow; Nell Meosky Luo; Christina Samaha; Unnati M. Pandya; Pushpamali De Silva; Sally Zhou; Zakary Ganhadeiro; Sara Yohannes; Rakiesha Gay; Jacqueline Slavik; Shibani S. Mukerji; Petr Jarolim; David R. Walt; Becky C. Carlyle; Lauren L. Ritterhouse; Sara Suliman

    doi:10.1101/2021.01.01.425028 Date: 2021-01-04 Source: bioRxiv

    The SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus MESHD) has accumulated multiple mutations during its global circulation. Recently, a new strain of SARS-CoV-2 (VUI 202012/01) had been identified leading to sudden spike in COVID-19 MESHD cases in South-East England. The strain has accumulated 23 mutations which have been linked to its immune evasion and higher transmission capabilities. Here, we have highlighted structural-function impact of crucial mutations occurring in spike (S), ORF8 PROTEIN and nucleocapsid (N) protein PROTEIN of SARS-CoV-2. Some of these mutations might confer higher fitness to SARS-CoV-2 MESHD. SummarySince initial outbreak of COVID-19 MESHD in Wuhan city of central China, its causative agent; SARS-CoV-2 virus has claimed more than 1.7 million lives out of 77 million populations and still counting. As a result of global research efforts involving public-private-partnerships, more than 0.2 million complete genome sequences have been made available through Global Initiative on Sharing All Influenza Data (GISAID). Similar to previously characterized coronaviruses (CoVs), the positive-sense single-stranded RNA SARS-CoV-2 genome codes for ORF1ab PROTEIN non-structural proteins (nsp(s)) followed by ten or more structural/nsps [1, 2]. The structural proteins include crucial spike (S), nucleocapsid (N PROTEIN), membrane (M), and envelope (E) proteins PROTEIN. The S protein PROTEIN mediates initial contacts with human hosts while the E and M proteins PROTEIN function in viral assembly and budding. In recent reports on evolution of SARS-CoV-2, three lineage defining non-synonymous mutations; namely D614G in S protein PROTEIN (Clade G), G251V in ORF3a PROTEIN (Clade V) and L84S in ORF 8 (Clade S) were observed [2-4]. The latest pioneering works by Plante et al and Hou et al have shown that compared to ancestral strain, the ubiquitous D614G variant (clade G) of SARS-CoV-2 exhibits efficient replication in upper respiratory tract epithelial cells and transmission, thereby conferring higher fitness MESHD [5, 6]. As per latest WHO reports on COVID-19 MESHD, a new strain referred as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) had been identified as a part of virological and epidemiological analysis, due to sudden rise MESHD in COVID-19 MESHD detected cases in South-East England [7]. Preliminary reports from UK suggested higher transmissibility (increase by 40-70%) of this strain, escalating Ro (basic reproduction number) of virus to 1.5-1.7 [7, 8]. This apparent fast spreading variant inculcates 23 mutations; 13 non-synonymous, 6 synonymous and 4 amino acid deletions [7]. In the current scenario, where immunization programs have already commenced in nations highly affected by COVID-19 MESHD, advent of this new strain variant has raised concerns worldwide on its possible role in disease severity and antibody responses. The mutations also could also have significant impact on diagnostic assays owing to S gene target failures.

    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.

    CRISPR-cas13 enzymology rapidly detects SARS-CoV-2 fragments in a clinical setting

    Authors: Wahab A. Khan; Rachael E. Barney; Gregory J Tsongalis

    doi:10.1101/2020.12.17.20228593 Date: 2020-12-19 Source: medRxiv

    The well-recognized genome editing ability of the CRISPR-Cas system has triggered significant advances in CRISPR diagnostics. This has prompted an interest in developing new biosensing applications for nucleic acid detection. Recently, such applications have been engineered for detection of SARS-CoV-2. Increased demand for testing and consumables of RT-qPCR assays has led to the use of alternate testing options in some cases. Here we evaluate the accuracy and performance of a novel fluorescence based assay that received EUA authorization from the FDA for detecting SARS-CoV-2 in clinical samples. The Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK) technology forms the basis of the Sherlock CRISPR SARS-CoV-2 kit using the CRISPR-Cas13a system. Our experimental strategy included selection of COVID-19 MESHD patient samples from previously validated RT-qPCR assays. Positive samples were selected based on a broad range of cycle thresholds. A total of 50 COVID-19 MESHD patient samples were correctly diagnosed with 100% accuracy (relative fluorescence ratios: N gene PROTEIN 95% CI 23.2-36.3, ORF1ab PROTEIN gene 95% CI 27.6-45.4). All controls, including RNase P, showed expected findings. Overall ratios were robustly distinct between positive and negative cases relative to the pre-established 5-fold change in fluorescence read output. We have evaluated the accuracy of detecting conserved targets of SARS-CoV-2 across a range of viral loads using the SHERLOCK CRISPR collateral detection reaction in a clinical setting. These findings demonstrate encouraging results, especially at a time when COVID-19 MESHD clinical diagnosis is in high demand; often with limited resources. This approach highlights new thinking in infectious disease MESHD identification and can be expanded to measure nucleic acids in other clinical isolates.

    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.

    Proteo-genomic analysis of SARS-CoV-2: A clinical landscape of SNPs, COVID-19 MESHD proteome and host responses

    Authors: Sheetal Tushir; Sathisha Kamanna; Sujith S Nath; Aishwarya Bhat; Steffimol Rose; Advait R Aithal; Utpal Tatu

    doi:10.1101/2020.11.27.20237032 Date: 2020-11-30 Source: medRxiv

    A novel severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the causative agent of COVID-19 MESHD and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic analysis using next generation sequencing (NGS) and mass-spectrometry on nasopharyngeal swabs of COVID-19 MESHD patients to examine clinical genome and proteome. Our study confirms the hyper mutability of SARS-CoV-2 showing multiple SNPs. NGS analysis detected 27 mutations of which 14 are synonymous, 11 are missense and 2 are extragenic in nature. Phylogenetic analysis of SARS-CoV-2 isolates indicated their close relation to Bangladesh isolate and multiple origins of isolates within a country. Our proteomic analysis, for the first time identified 13 different SARS-CoV-2 proteins from the clinical swabs. Of the total 41 peptides captured by HRMS, 8 matched to nucleocapsid protein PROTEIN, 2 to ORF9b PROTEIN, 1 to spike glycoprotein PROTEIN and ORF3a PROTEIN, with remaining mapping to ORF1ab PROTEIN polyprotein. Additionally, host proteome analysis revealed several key host proteins to be uniquely expressed in COVID-19 MESHD patients. Pathway analysis of these proteins points towards modulation in immune response, especially involving neutrophil and IL-12 mediated signaling. Besides revealing the aspects of host-virus pathogenesis, our study opens new avenues to develop better diagnostic markers and therapeutics.

    Dynamics of ORF1ab PROTEIN and N Gene PROTEIN among hospitalized COVID-19 MESHD positive cohorts: A hospital based retrospective study

    Authors: Pojul Loying; Vaishali Sarma; Suranjana C. Hazarika; Monjuri Kataki; Dina Raja; Divyashree Medhi; Ridip Dutta; Achu Chena; Divya Daimary; Aakangkhita Choudhurydo; Lahari Saikia

    doi:10.1101/2020.11.22.20236240 Date: 2020-11-23 Source: medRxiv

    Objective: The present study hospital based retrospective study aimed at investigating the dynamics of ORF1ab PROTEIN and N gene PROTEIN from hospitalized COVID-19 MESHD positive cohorts considering the Ct values of both genes. Study design and Methodology: Retrospective analyses of Ct values were done from 115 hospitalized COVID-19 MESHD positive patients in different time interval. Patients were admitted to the hospital either by RAT or/and RT-PCR and first RT-PCR testing were made after 9 days of incubation followed by testing in every 3 days of interval till negative, subsequently release of the patients. Results: We have looked into the dynamics of ORF1ab PROTEIN and N gene PROTEIN and found that N gene PROTEIN require longer duration of days with 12.68 (S.D.=3.24) to become negative than ORF1ab PROTEIN with 12.09 (S.D.=2.88) days and it differs significantly (p=0.012; p<0.05). The persistent of N gene PROTEIN found in 46 patients out of 115 (39.65%) to the succeeding reading after 3 days. We have also looked into the mean differences in the between N and ORF1ab PROTEIN genes every readings separately and found that there were no significant differences between the mean Ct value of ORF1ab PROTEIN and N gene PROTEIN except in the day 3 (p=0.015; p<0.05). Further, we have looked into the relationship of age and gender of patients with the duration of positivity; however we did not find any significant role. Conclusion: In COVID-19 MESHD hospital positive cohorts, the persistent of positivity of N gene PROTEIN is significantly for more duration than ORF1ab PROTEIN. As the SARS-CoV-2 is a new virus and study on it is evolving, so, exhaustive study is required on the dynamic of N gene PROTEIN positivity persistent in relation to the other pathophysiological parameters for the management and control of COVID-19 MESHD.

    Long-term monitoring of SARS-CoV-2 in wastewater of the Frankfurt metropolitan area in Southern Germany

    Authors: Shelesh Agrawal; Laura Orschler; Susanne Lackner

    doi:10.1101/2020.10.26.20215020 Date: 2020-10-27 Source: medRxiv

    Wastewater-based epidemiology (WBE) is a great approach that enables us to comprehensively monitor the community to determine the scale and dynamics of infections in a city, particularly in metropolitan cities with a high population density. Therefore, we monitored the time course of the SARS-CoV-2 RNA concentration in raw sewage in the Frankfurt metropolitan area, the European financial center. To determine the SARS-CoV-2 concentration in sewage, we continuously collected samples from two wastewater treatment plant (WWTP) influents (Niederrad and Sindlingen) serving the Frankfurt metropolitan area and performed RT-qPCR analysis targeting three genes (N PROTEIN gene, S gene, and ORF1ab PROTEIN gene). In August, a resurgence in the SARS-CoV-2 RNA load was observed, reaching 3 x 10^13 copies/day, which represents similar levels compared to April with approx. 2 x 10^14 copies/day. This corresponds to an also continuous increase again in COVID-19 MESHD cases in Frankfurt since August, with an average of 28.6 incidences, compared to 28.7 incidences in April. Different temporal dynamics were observed between different sampling points, indicating local dynamics in COVID-19 MESHD cases within the Frankfurt metropolitan area. The SARS-CoV-2 load to the WWTP Niederrad ranged from approx. 4 x 10^11 to 1 x 10^15 copies/day, the load to the WWTP Sindlingen from approx. 1 x 10^11 to 2 x 10^14 copies/day, which resulted in a preceding increase in these loading in July ahead of the weekly averaged incidences. The study shows that WBE has the potential as early warning system for SARS-CoV-2 infections MESHD and as monitoring system to identify global hotspots of COVID 19.

    Development and comparison of a novel multiple cross displacement amplification (MCDA) assay with other nucleic acid amplification methods for SARS-CoV-2 detection

    Authors: Laurence Don Wai Luu; Michael J Payne; Xiaomei Zhang; Lijuan Luo; Ruiting Lan

    doi:10.1101/2020.10.03.20206193 Date: 2020-10-06 Source: medRxiv

    Objectives: To develop a novel multiple cross displacement amplification (MCDA) assay for COVID-19 MESHD and compare its speed and sensitivity to existing loop-mediated isothermal amplification (LAMP) and real-time PCR (RT-PCR) methods. Methods: Two MCDA assays targeting the SARS-CoV-2 N gene PROTEIN and ORF1ab PROTEIN was designed. The fastest time to detection and sensitivity of MCDA was compared to LAMP and RT-PCR using 7 DNA standards and transcribed RNA. Results: For the N gene PROTEIN, MCDA was consistently faster than LAMP and RT-PCR by 10 and 20 minutes, respectively with a fastest time to detection of 5.2 minutes. RT-PCR had the highest sensitivity with a limit of detection of 100 copies/reaction compared with MCDA (1000 copies/reaction) and LAMP (5000/reaction). For ORF1ab PROTEIN, MCDA and LAMP had similar speed with fastest time to detection at 9.7 and 8.4 minutes, respectively. LAMP was more sensitive for ORF1ab PROTEIN detection with 500 copies/reaction compared to MCDA (5000 copies/reaction). Conclusions: Different nucleic acid amplification methods provide different advantages. MCDA is the fastest nucleic acid amplification method for COVID-19 MESHD while RT-PCR is still the most sensitive. These advantages should be considered when determining the most suitable nucleic acid amplification methods for different applications.

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