Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF1a (36)

ProteinS (13)

ProteinN (7)

ORF1ab (6)

ComplexRdRp (4)


SARS-CoV-2 Proteins
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    Multiplex Fragment Analysis Identifies SARS-CoV-2 Variants

    Authors: Andrew E Clark; Zhaohui Wang; Brandi L Cantarel; Mohammed Kanchwala; Chao Xing; Li Chen; Pei Irwin; Yan Xu; Dwight Oliver; Francesca Lee; Jeffrey R Gagan; Jason Y Park; Laura Filkins; Alagarraju Muthukumar; Ravi Sarode; Jeffrey A SoRelle

    doi:10.1101/2021.04.15.21253747 Date: 2021-04-16 Source: medRxiv

    The rapid spread of SARS-CoV-2 variants are of critical concern, necessitating systematic efforts for epidemiological surveillance. The current method for identifying variants is viral genome sequencing. Sequencing has multiple limitations to broad clinical adoption including requirements for technical expertise, expense of equipment and bioinformatics, and time for implementation. Here we describe a scalable non-sequencing-based capillary electrophoresis assay to affordably screen variants of SARS-CoV-2. The assay has targets for N1 (CDC nucleocapsid target, internal control), spike gene 69_70 deletion, spike gene 144 deletion, and ORF1A PROTEIN 3675_3677 deletion, which are all present in the B.1.1.7 (UK) variant. ORF1A PROTEIN deletions alone are also present in the New York, Brazil, and South African variants. 648 specimens have been tested to date and the assay is able to detect the B.1.1.7 variant 32 times (n=23 specimens, n=9 positive control replicates). Additionally, the B.1.429 (California) variant can be detected when a 3bp insertion or drop out of the S144 target is present. 7/23 B.1.1.7 specimens have been confirmed by Whole Genome Sequencing (16 pending confirmation), and demonstrate the ability to rapidly track the progression of COVID-19 MESHD variants in the population.

    SARS-CoV-2 UK, South African and Brazilian Variants in Karachi- Pakistan

    Authors: Adnan Khan; Muhammad Hanif; Sarosh Syed; Akhtar Ahmed; Saqib Ghazali; Rafiq Khanani

    doi:10.1101/2021.04.09.21255179 Date: 2021-04-13 Source: medRxiv

    COVID-19 pandemic MESHD has been evolving in Pakistan since the UK, South African and Brazilian variants have started surfacing which are known for increase transmissibility and can also be responsible for escape from immune responses. The gold standard to detect these variants of concern is sequencing, however routine genomic surveillance in resource limited countries like Pakistan is not always readily available. With the emergence of variants of concern and a dearth of facilities for genomic scrutiny leaves policy makers and health authorities an inconsistent and twisted image to make decisions. The inadvertent detection of B.1.1.7 by target failure because of a key deletion in spike {Delta}69-70 in the UK by commercially available COVID-19 MESHD PCR assay helps to understand target failures as an alternative approach to detect variants. It was ascertained further that a deletion in the ORF1a PROTEIN gene ( ORF1a PROTEIN {Delta}3675-3677) found common in B.1.1.7, B.135 and P.1 variants of concern. The Real Time Quantitative PCR (RT-qPCR) assay for detection of emergence and spread of SARS-CoV-2 variants, by these target failures is used here. The positive samples archived in respective labs were divided in two groups used in the present study. Group I constitutes 261 positive samples out of 16964 (1.53%) collected from August till September 2020. Group II include 3501 positive samples out of 46041 (7.60%) from November 2020 till January 2021. In positive samples of group I, no variant of concern was found. A staggering difference in results was noted in group II where positivity ratio increased exponentially and the variants of concern started appearing in significant numbers (53.64% overall). This is indicative that the third wave in Pakistan is due to the importation of SARS-CoV-2 variants. This calls for measures to increase surveillance by RT-qPCR which would help authorities in decision making.

    Emergence of multiple SARS-CoV-2 antibody escape variants in an immunocompromised host undergoing convalescent plasma treatment

    Authors: Liang Chen; Michael C Zody; Jose R Mediavilla; Marcus H Cunningham; Kaelea Composto; Kar Fai Chow; Milena Kordalewska; Andre Corvelo; Dayna M Oschwald; Samantha Fennessey; Marygrace Zetkulic; Sophia Dar; Yael Kramer; Barun Mathema; Tom Maniatis; David S Perlin; Barry N Kreiswirth

    doi:10.1101/2021.04.08.21254791 Date: 2021-04-11 Source: medRxiv

    SARS-CoV-2 Variants of Concerns (VOC), e.g., B.1.351 (20H/501Y.V2) and P1 (20J/501Y.V3), harboring N-terminal domain ( NTD HGNC) or the receptor-binding domain (RBD) (e.g., E484K) mutations, exhibit reduced in vitro susceptibility to convalescent serum, commercial antibody cocktails, and vaccine neutralization, and have been associated with reinfection. The accumulation of these mutations could be the consequence of intra-host viral evolution due to prolonged infection MESHD in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on tacrolimus, steroids and convalescent plasma therapy, and identify the emergence of multiple NTD HGNC and RBD mutations associated with reduced antibody neutralization as early as three weeks after infection. SARS-CoV-2 genomes from the first swab (Day 0) and three tracheal aspirates (Day 7, 21 and 27) were compared at the sequence level. We identified five different S protein PROTEIN mutations at the NTD HGNC or RBD regions from the second tracheal aspirate sample (21 Day). The S:Q493R substitution and S:243-244LA deletion had ~70% frequency, while ORF1a PROTEIN:A138T, S:141-144LGVY deletion, S:E484K and S:Q493K substitutions demonstrated ~30%, ~30%, ~20% and ~10% mutation frequency, respectively. However, the third tracheal aspirate sample collected one week later (Day 27) was predominated by the haplotype of ORF1a PROTEIN:A138T, S:141-144LGVY deletion and S:E484K (> 95% mutation frequency). Notably, S protein PROTEIN deletions (141-144LGVY and 243-244LA deletions in NTD HGNC region) and substitutions (Q493K/R and E484K in the RBD region) previously showed reduced susceptibly to monoclonal antibody or convalescent plasma. The observation supports the hypothesis that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune-escape mutants.

    To knot and not: Multiple conformations of the SARS-CoV-2 frameshifting RNA element

    Authors: Tamar Schlick; Qiyao Zhu; Abhishek Dey; Swati Jain; Shuting Yan; Alain Laederach

    doi:10.1101/2021.03.31.437955 Date: 2021-04-01 Source: bioRxiv

    The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19 MESHD. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a PROTEIN and 1b, which code for viral polyproteins. Any interference with this process has profound effect on viral replication and propagation. Pinpointing the structures adapted by the FSE and associated structural transformations involved in frameshifting has been a challenge. Using our graph-theory-based modeling tools for representing RNA secondary structures, "RAG" (RNA-As-Graphs), and chemical structure probing experiments, we show that the 3-stem H-type pseudoknot (3_6 dual graph), long assumed to be the dominant structure, is replaced by a different, HL-type 3-stem pseudoknot (3_3) as more residues, in particular the slippery site's 7 residues, are considered. In addition, an unknotted 3-way junction RNA (3_5) emerges as a minor conformation. These three conformations share Stems 1 and 3, while the different Stem 2 may be involved in a conformational switch and possibly associations with the ribosome during translation. These structural and mechanistic insights advance our understanding of the SARS-CoV-2 frameshifting process and concomitant virus life cycle, and point to three avenues of therapeutic intervention.

    PCR assay to enhance global surveillance for SARS-CoV-2 variants of concern

    Authors: Chantal BF Vogels; Mallery Breban; Tara Alpert; Mary E Petrone; Anne E Watkins; Emma Hodcroft; Christopher E Mason; Gaurav Khullar; Joel T Dudley; Matthew J Mackay; Jianhui Wang; Chen Liu; Pei Hui; Steven Murphy; Caleb Neal; Eva Laszlo; Marie L Landry; Anthony Muyombwe; Randy Downing; Jafar Razeq; Richard A Neher; Joseph R Fauver; Nathan D Grubaugh

    doi:10.1101/2021.01.28.21250486 Date: 2021-02-01 Source: medRxiv

    With the emergence of SARS-CoV-2 variants that may increase transmissibility and/or cause escape from immune responses1-3, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant first detected in the UK4,5 could be serendipitously detected by the ThermoFisher TaqPath COVID-19 MESHD PCR assay because a key deletion in these viruses, spike {Delta}69-70, would cause a 'spike gene target failure' (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern that lack spike {Delta}69-70, such as B.1.351 (also 501Y.V2) detected in South Africa6 and P.1 (also 501Y.V3) recently detected in Brazil7. We identified a deletion in the ORF1a PROTEIN gene ( ORF1a PROTEIN {Delta}3675-3677) in all three variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a PROTEIN {Delta}3675-3677 as the primary target and spike {Delta}69-70 to differentiate, we designed and validated an open source PCR assay to detect SARS-CoV-2 variants of concern8. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence spread of B.1.1.7, B.1.351, and P.1.

    Effect of Heat Inactivation for the Detection of Severe Acute Respiratory Syndrome-Corona Virus-2 MESHD (SARS-CoV-2) with Reverse Transcription Real Time Polymerase Chain Reaction (rRT-PCR): Evidence from Ethiopian Study

    Authors: Belete Woldesemayat Hailemariam; Gebremedihin Gebremicael; Kidist Zealias; Amelework Yilma; Sisay Adane; Mengistu Yimer; Gadissa Gutema; Altaye Feleke; Kassu Desta

    doi:10.21203/ Date: 2021-01-23 Source: ResearchSquare

    Background: Coronavirus disease 2019 MESHD ( COVID-19 MESHD) specimen handling needs a major concern due to the virus has a potential of easily transmittable to health care workers and laboratory personnel. Heat inactivation before nucleic acid isolation might permit safe testing, even though, the effect of heat inactivation on SARS-CoV-2 RT-PCR detection results needs to be determined. Methods: An experimental study was conducted in Ethiopian Public Health Institute (EPHI) from September 25 to October 15, 2020. A total of 188 Oro-pharyngeal swabs were collected from COVID-19 MESHD suspected cases, referred to EPHI for SARS COV-2 testing during the study period. One group of the sample was inactivated at 56 °C heat for 30 min, and the other group was stored at 4°C for a similar period of time. RNA extraction and detection were done by DAAN Gene extraction and detection kit. Abbott m2000 RT-PCR was used for amplification and detection. Data analysis was done by using SPSS version 23.0; Chi-square and Pearson correlation test for qualitative and semi-quantitative analysis were used. P-value < 0.05 was considered as statistically significant.Results: Out of 188 total samples, 117 (62.2 %) and 118 (62.8%) were positive for ORF1a PROTEIN/b and N gene PROTEIN respectively before inactivation. Whereas after inactivation, 111 (59 %) was ORF1a PROTEIN/b and 116 (61.7 %) was N gene PROTEIN positive. Rate of positivity between groups was not statistically significant (p>0.05). The mean CT value difference between the two groups of ORF1a PROTEIN/b gene and N PROTEIN gene was 0.042 (95 % CI, -0.247- 0.331; t= 0.28; p = 0.774) and 0.38 (95% CI, 0.097 - 0.682; t =2.638; p = 0.010) respectively.Conclusion: Heat inactivation at 56 ℃ for 30 min has not statistically significant effect for the qualitative rRT-PCR detection of SARS-CoV-2. However, the finding also showed that there was statistically significant CT value increment after heat inactivation compared to untreated samples. Therefore, false-negative results with high CT value results (CT > 35) were found to be the challenge of this protocol. Hence alternative inactivation methods should be investigated and further studies should be considered.  

    Genomic diversity analysis of SARS-CoV-2 genomes in Rwanda

    Authors: Nzungize Lambert; Ndishimye Pacifique; Fathiah Zakham; François Balloux; Meghna Sobti; Peter Schofield; Helen Lenthall; Jennifer Jackson; Stephanie Ubiparipovic; Jake Y Henry; Arunasingam Abayasingam; Deborah Burnett; Anthony Kelleher; Robert Brink; Rowena A Bull; Stuart Turville; Alastair G Stewart; Christopher C Goodnow; William D Rawlinson; Daniel Christ; Randeep Guleria; Krishna Ella; Balram Bhargava; Steven De Jonghe; Jasper Rymenants; Vincenzo Summa; Enzo Tramontano; Andrea Rosario Beccari; Pieter Leyssen; Paola Storici; Johan Neyts; Philip Gribbon; Andrea Zaliani

    doi:10.1101/2020.12.14.422793 Date: 2020-12-15 Source: bioRxiv

    COVID-19 MESHD ( Coronavirus disease 2019 MESHD) is an emerging pneumonia-like respiratory disease MESHD of humans and is recently spreading across the globe. To analyze the genome sequence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2 MESHD) isolated from Rwanda with other viral strains from African countries. We downloaded 75 genomes sequences of clinical SARS-CoV-2 from the GISAID (global initiative on sharing all influenza data) database and we comprehensively analyzed these SARS-CoV-2 genomes sequences alongside with Wuhan SARS-CoV-2 MESHD sequences as the reference strains. We analyzed 75 genomes sequences of SARS-CoV-2 isolated in different African countries including 10 samples of SARS-CoV-2 isolated in Rwanda between July and August 2020. The phylogenetic analysis of the genome sequence of SARS-CoV-2 revealed a strong identity with reference strains between 90-95%. We identified a missense mutation in four proteins including orf1ab polyprotein, NSP2 HGNC NSP2 PROTEIN, 2'-O-ribose methyltransferase and orf1a PROTEIN polyprotein. The most common changes in the base are C > T. We also found that all clinically SARS-CoV-2 isolated from Rwanda had genomes belonging to clade G and lineage B.1. Tracking the genetic evolution of SARS-CoV-2 over time is important to understand viral evolution pathogenesis. These findings may help to implement public health measures in curbing COVID-19 MESHD in Rwanda.

    Immunoinformatics approach for multi-epitope vaccine design against structural proteins and ORF1a PROTEIN polyproteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

    Authors: Khalid Mohamed Adam

    doi:10.21203/ Date: 2020-11-15 Source: ResearchSquare

    Background The lack of effective treatment and a protective vaccine against the highly infectious SARS-CoV-2 has aggravated the already catastrophic global health issue. Here, in an attempt to design an efficient vaccine, a vigorous immunoinformatics approach was followed to predict the most suitable viral proteins epitopes for building that vaccine.Methods The amino acid sequences of four structural proteins (S PROTEIN, M, N, E) along with one potentially antigenic accessory protein ( ORF1a PROTEIN) of SARS-CoV-2 were inspected for the most appropriate epitopes to be used for building the vaccine construct. Several immunoinformatics tools were used to assess the antigenicity, immunogenicity, allergenicity, toxigenicity, interferon-gamma HGNC inducing capacity, and the physicochemical properties of the product.Results The final candidate vaccine construct consisted of 468 amino acids, encompassing 30 epitopes. All the vaccine properties and its ability to trigger the humoral and cell-mediated immune response were validated computationally. Molecular modeling, docking to TLR3 HGNC, simulation, and molecular dynamics were also carried out. Finally, a molecular clone using pET28: :mAID expression plasmid vector was prepared.Conclusion The overall results of the study suggest that the final multi-epitope chimeric construct is a potential candidate for an efficient protective vaccine against SARS-CoV-2.

    A gapless unambiguous RNA metagenome-assembled genome sequence of a unique SARS-CoV-2 variant encoding spike S813I and ORF1a PROTEIN A859V substitutions

    Authors: May Sherif Soliman; May AbdelFattah; Soad M. N. Aman; Lamyaa M. Ibrahim; Ramy Karam Aziz

    doi:10.21203/ Date: 2020-10-25 Source: ResearchSquare

    The novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2 MESHD) is causing an unprecedented pandemic, threatening global health, daily life, and economy. Genomic surveillance continues to be a critical effort towards tracking the virus and containing its spread, and more genomes from diverse geographical areas and different time points are needed to provide an appropriate representation of the virus evolution. We here report the successful assembly of one single gapless, unambiguous contiguous sequence representing the complete viral genome from a nasopharyngeal swab of an infected healthcare worker in Cairo, Egypt. The sequence has all typical features of SARS-CoV-2 genomes, with no protein-disrupting mutations; however, three mutations are worth highlighting and future tracking: a synonymous mutation causing a rare spike S-813-I variation) and two less frequent ones leading to an A41V variation in NSP3 PROTEIN, encoded by ORF1a PROTEIN ( ORF1a PROTEIN A895V), and a Q677H variation in the spike protein PROTEIN. Both affected proteins, S PROTEIN and NSP3 PROTEIN, are relevant to vaccine and drug development. While the genome, named CU_S3, belongs to the prevalent global genotype, marked by the D614G spike variation, the combined variations in the spike proteins PROTEIN and ORF1a PROTEIN have not been observed in any of the 197,000 genomes reported to date. Future studies will assess the biological, pathogenic, and epidemiologic implications of this set of genetic variations.

    Phylogeographic analysis of SARS-CoV-2 variations from Indian isolates

    Authors: Akshat Joshipura; S Balaji

    doi:10.21203/ Date: 2020-10-09 Source: ResearchSquare

    The aggressive multiplication of coronavirus in the Indian population is probably due to the faster mutation rate. At the time of commencement of this work, India was not present in the list of Top 10 worst-affected countries. However, upon completion of this manuscript, India is ranked No. 3 and during publication of this manuscript it may even elevate to the top two positions due to the pandemic. In this study, SARS-CoV-2 isolates of Indian origin were compared with the Wuhan reference sequence. Phylogenomic, proteomic, and phylogeographic analyses were performed. The genome comparisons indicated that majority of the sequence variations are associated with protein-coding regions, especially Orf1a PROTEIN and spike glycoproteins PROTEIN, while Orf7a PROTEIN had consistent variations, whereas Orfs 6a, 8 and 10 had negligible variations. The terminals of the genomes compared had high sequence entropy. However, the polyadenylation signal was invariant in the analysed dataset. The codon usage frequency indicated that UGU (code for cysteine) is the most frequent codon, while the least frequent was GCG (code for alanine). The amino acid frequency showed that the most abundant was leucine (12.5%), and the least was histidine (2.45%). The phylogeographical patterns were mapped for all the representative states of India, and were supplemented with few representative countries. The unique differences in the sequence of the Kerala isolate (EPI_ISL_413522) were resolved to be sequence errors rather than mutations. Based on the phylogeographic analysis, the high probability of mutations likely to be of Indian origin is attributed to the Gujarat cluster.  

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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