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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinE (128)

ProteinS (35)

ProteinN (32)

ProteinM (17)

ComplexRdRp (16)


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SARS-CoV-2 Proteins
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    Targeted Drug Repurposing Against the SARS-CoV-2 E Channel Identifies Blockers With in vitro Antiviral Activity

    Authors: Prabhat Pratap Singh Tomar; Miriam Krugliak; Isaiah T Arkin

    doi:10.1101/2021.02.24.432490 Date: 2021-02-24 Source: bioRxiv

    It is difficult to overstate the impact that COVID-19 MESHD had on humankind. The pandemic's etiological agent, SARS-CoV-2, is a member of the Coronaviridae, and as such, is an enveloped virus with ion channels in its membrane. Therefore, in an attempt to provide an option to curb the viral spread, we searched for blockers of its E protein PROTEIN viroporin. Using three bacteria-based assays, we identified eight compounds that exhibited activity after screening a library of ca. 3000 approved-for-human-use drugs. Reassuringly, analysis of viral replication in tissue culture indicated that most of the compounds could reduce infectivity to varying extents. In conclusion, targeting a particular channel in the virus for drug repurposing may increase our arsenal of treatment options to combat COVID-19 MESHD virulence.

    Delivery of recombinant SARS-CoV-2 envelope protein PROTEIN into human cells

    Authors:

    doi:10.1101/2021.02.18.431684 Date: 2021-02-19 Source: bioRxiv

    SARS-CoV-2 envelope protein PROTEIN (S2-E) is a conserved membrane protein that is essential to coronavirus assembly and budding. Here, we describe the recombinant expression and purification of S2-E into amphipol-class amphipathic polymer solutions. The physical properties of amphipols underpin their ability to solubilize and stabilize membrane proteins without disrupting membranes. Amphipol delivery of S2-E to pre-formed planar bilayers results in spontaneous membrane integration and formation of viroporin ion channels. Amphipol delivery of the S2- E protein PROTEIN to human cells results in membrane integration followed by retrograde trafficking to a location adjacent to the endoplasmic reticulum-to-Golgi intermediate compartment (ERGIC) and the Golgi, which are the sites of coronavirus replication. Delivery of S2-E to cells enables both chemical biological approaches for future studies of SARS-CoV-2 pathogenesis MESHD and development of "Trojan Horse" anti-viral therapies. This work also establishes a paradigm for amphipol-mediated delivery of membrane proteins to cells.

    An alternative approach for bioanalytical assay development for wastewater-based epidemiology of SARS-CoV-2

    Authors: Tim Boogaerts; Lotte Jacobs; Naomi De Roeck; Siel Van den Bogaert; Bert Aertgeerts; Lies Lahousse; Alexander L.N. van Nuijs; Peter Delputte

    doi:10.1101/2021.02.12.21251626 Date: 2021-02-16 Source: medRxiv

    Wastewater-based epidemiology could be applied to track down SARS-CoV-2 outbreaks at high spatio-temporal resolution and could potentially be used as an early-warning for emergence of SARS-CoV-2 circulation in the general population. Epidemiological surveillance of SARS-CoV-2 could play a role in monitoring the spread of the virus in the population and controlling possible outbreaks. However, sensitive sample preparation and detection methods are necessary to detect trace levels of SARS-CoV-2 RNA in influent wastewater (IWW). Unlike predecessors, method development of a SARS-CoV-2 RNA concentration and detection procedure was performed with IWW samples with high viral SARS-CoV-2 loads (in combination with seeding IWW with a surrogate coronavirus). This is of importance since the SARS-CoV-2 genome in IWW might have already been subject to in-sewer degradation into smaller genome fragments or might be present in a different form (e.g. cell debris,...). Centricon Plus-70 (100 kDa) centrifugal filter devices resulted in the lowest and most reproducible Ct-values for SARS-CoV-2 RNA. Lowering pore sizes did not improve our limit of detection and quantification. Real-time polymerase chain reaction (qPCR) was employed for the amplification of the N1, N2, N3 and E_Sarbeco-gene. This is one of the first studies to apply digital polymerase chain reaction (dPCR) for the detection of SARS-CoV-2 RNA in IWW. Interestingly, qPCR results were comparable with dPCR results suggesting that qPCR is a valid method. In this study, dPCR was also used as a proxy to assess the precision of qPCR. In this light, dPCR showed high variability at low concentration levels (100 copies/{micro}L), indicating that variability in bioanalytical assays for SARS-CoV-2 RNA might be substantial. On average, the N2-gene showed high in-sample stability in IWW for 10 days of storage at 4 {degrees}C. Between-sample variability was substantial due to the low native concentrations in IWW. Additionally, the E-gene PROTEIN proved to be less stable compared to the N2-gene and showed higher variability. Freezing the IWW samples resulted in a 10-fold decay of loads of the N2- and E-gene PROTEIN in IWW. Although WBE can already aid in filling some knowledge gaps in the epidemiological surveillance of SARS-CoV-2, future WBE studies should aim to further validate and standardize bioanalytical assays, especially with regards to methodological limitations. HighlightsO_LIDevelopment of an analytical procedure for detection of SARS-CoV-2 RNA in wastewater C_LIO_LIExtraction recovery was evaluated in influent wastewater C_LIO_LIPrecision measured with dPCR used as a proxy for qPCR C_LIO_LIqPCR of the N2 gene fragment showed high in-sample stability of SARS-CoV-2 on average C_LI

    Vaccine Design, Adaptation, and Cloning Design for Multiple Epitope-Based Vaccine Derived From SARS-CoV-2 Surface Glycoprotein (S PROTEIN), Membrane Protein (M PROTEIN) and Envelope Protein (E PROTEIN): In silico approach

    Authors: Peter T. Habib

    doi:10.21203/rs.3.rs-241638/v1 Date: 2021-02-14 Source: ResearchSquare

    The SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global epidemic that has increased the scientific community's concern about developing and finding a counteraction against this lethal virus. So far, hundreds of thousands of people have been infected by the pandemic due to contamination and spread. This research was therefore carried out to develop potential epitope-based vaccines against the SARS-CoV-2 virus using reverse vaccinology and immunoinformatics approaches. Three potential vaccine constructs were designed after intensive computational experimentation, and one vaccine model was chosen as the best vaccine based on a molecular docking analysis that is intended to work efficiently against SARS-CoV-2. In order to verify biological stability and find an appropriate mass production technique for the chosen vaccine, molecular dynamics simulation, and silico codon adaptation studies were subsequently carried out. This study should help to maintain current research efforts to secure a definitive preventive measure against this contagious disease.

    Designing a new multi epitope-based vaccine against COVID-19 MESHD disease: an immunoinformatic study based on reverse vaccinology approach

    Authors: Afshin Samimi Nemati; Majid Tafrihi; Fatemeh Sheikhi; Abolfazl Rostamian Tabari; Amirhossein Haditabar

    doi:10.21203/rs.3.rs-206270/v1 Date: 2021-02-04 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has currently caused a significant pandemic among worldwide populations. The transmission speed and the high rate of mortality caused by the disease necessitate studies for the rapid designing and effective vaccine production. The purpose of this study is to predict and design a novel multi-epitope vaccine against the SARS-CoV-2 virus using bioinformatics approaches. Coronavirus envelope proteins PROTEIN, ORF7b PROTEIN, ORF8 PROTEIN, ORF10 PROTEIN, and NSP9 PROTEIN were selected as targets for epitope mapping using IEDB and BepiPred 2.0 Servers. Also, molecular docking studies were performed to determine the candidate vaccine's affinity to TLR3 HGNC, TLR4 HGNC, MHC I, and MHC II molecules. Thirteen epitopes were selected to construct the multi-epitope vaccine. We found that the constructed peptide has valuable antigenicity, stability, and appropriate half-life. The Ramachandran plot approved the quality of the predicted model after the refinement process. Molecular docking investigations revealed that antibody-mode in the Cluspro 2.0 server showed the lowest binding energy for MHCI, MHCII, TLR3 HGNC, and TLR4 HGNC. This study confirmed that the designed vaccine has a good antigenicity and stability and could be a proper vaccine candidate against the COVID-19 MESHD infectious disease MESHD though, in vitro and in vivo experiments are necessary to complete and confirm our results.

    Host PDZ-containing proteins targeted by SARS-Cov-2

    Authors: Celia Caillet-Saguy; Fabien Durbesson; Veronica V. REZELJ; Gergo Gogl; Quang Dinh Tran; Jean-Claude Twizere; Marco Vignuzzi; Renaud Vincentelli; Nicolas Wolff; Rahaf Alharbi; Mazen Hassanain; Anwar M Hashem; Eugene B. Chang; Glenn Randall; Pablo Penaloza-MacMaster; Bozhi Tian; Maria Lucia Madariaga; Jun Huang; Dirk Jochmans; Birgit Weynand; Johan Neyts

    doi:10.1101/2021.02.01.429176 Date: 2021-02-01 Source: bioRxiv

    Small linear motif targeting protein interacting domains called PDZ have been identified at the C-terminus of the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) proteins E PROTEIN, 3a, and N. Using a high-throughput approach of affinity-profiling against the full human PDZome, we identified sixteen human PDZ binders of SARS-CoV-2 proteins E PROTEIN, 3A and N showing significant interactions with dissociation constants values ranging from 3 M to 82 M. Six of them ( TJP1 HGNC, PTPN13 HGNC, HTRA1 HGNC, PARD3 HGNC, MLLT4 HGNC, LNX2 HGNC) are also recognized by SARS-CoV while three ( NHERF1 HGNC, MAST2 HGNC, RADIL HGNC) are specific to SARS-CoV-2 E protein PROTEIN. Most of these SARS-CoV-2 protein partners are involved in cellular junctions/polarity and could be also linked to evasion mechanisms of the immune responses during viral infection MESHD. Seven of the PDZ-containing proteins among binders of the SARS-CoV-2 proteins E PROTEIN, 3a or N affect significantly viral replication under knock-down gene expression in infected cells. This PDZ profiling identifying human proteins potentially targeted by SARS-CoV-2 can help to understand the multifactorial severity of COVID19 MESHD and to conceive effective anti-coronaviral agents for therapeutic purposes.

    Expression of human ACE2 HGNC N-terminal domain, part of the receptor for SARS-CoV-2, in fusion with maltose binding protein, E PROTEIN. coli ribonuclease I and human RNase A

    Authors: Shuang-yong Xu; Alexey Fomenkov; Tien-Hao Chen; Erbay Yigit; Yinhui Lu; Karl E Kadler

    doi:10.1101/2021.01.31.429007 Date: 2021-02-01 Source: bioRxiv

    The SARS-CoV-2 viral genome contains a positive-strand single-stranded RNA of ~30 kb. Human ACE2 HGNC protein is the receptor for SARS-CoV-2 virus attachment MESHD and initiation of infection MESHD. We propose to use ribonucleases (RNases) as antiviral agents to destroy the viral genome in vitro. In the virions the RNA is protected by viral capsid proteins, membrane proteins and nucleocapsid PROTEIN proteins. To overcome this protection we set out to construct RNase fusion with human ACE2 HGNC receptor N-terminal domain (ACE2NTD). We constructed six proteins expressed in E. coli cells: 1) MBP-ACE2NTD, 2) ACE2NTD-GFP, 3) RNase I (6xHis), 4) RNase III (6xHis), 5) RNase I-ACE2NTD (6xHis), and 6) human RNase A HGNC-ACE2NTD150 (6xHis). We evaluated fusion expression in different E. coli strains, partially purified MBP-ACE2NTD protein from the soluble fraction of bacterial cell lysate, and refolded MBP-ACE2NTD protein from inclusion body. The engineered RNase I-ACE2NTD (6xHis) and hRNase A-ACE2NTD (6xHis) fusions are active in cleaving COVID-19 MESHD RNA in vitro. The recombinant RNase I (6xHis) and RNase III (6xHis) are active in cleaving RNA and dsRNA in test tube. This study provides a proof-of-concept for construction of fusion protein between human cell receptor and nuclease that may be used to degrade viral nucleic acids in our environment.

    BRD2 HGNC inhibition blocks SARS-CoV-2 infection MESHD in vitro by reducing transcription of the host cell receptor ACE2

    Authors: Ruilin Tian; Avi J Samelson; Veronica V Rezelj; Merissa Chen; Gokul N Ramadoss; Xiaoyan Guo; Alice Mac Kain; Quang Dinh Tran; Shion A Lim; Irene Lui; James Nunez; Sarah J Rockwood; Na Liu; Jared Carlson-Stevermer; Jennifer Oki; Travis Maures; Kevin Holden; Jonathan S Weissman; James A Wells; Bruce Conklin; Marco Vignuzzi; Martin Kampmann; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.19.427194 Date: 2021-01-19 Source: bioRxiv

    SARS-CoV-2 infection MESHD of human cells is initiated by the binding of the viral Spike protein PROTEIN to its cell-surface receptor ACE2 HGNC. We conducted an unbiased CRISPRi screen to uncover druggable pathways controlling Spike protein PROTEIN binding to human cells. We found that the protein BRD2 HGNC is an essential node in the cellular response to SARS-CoV-2 infection MESHD. BRD2 HGNC is required for ACE2 HGNC transcription in human lung epithelial cells and cardiomyocytes, and BRD2 HGNC inhibitors currently evaluated in clinical trials potently block endogenous ACE2 HGNC expression and SARS-CoV-2 infection MESHD of human cells. BRD2 HGNC also controls transcription of several other genes induced upon SARS-CoV-2 infection MESHD, including the interferon response, which in turn regulates ACE2 HGNC levels. It is possible that the previously reported interaction between the viral E protein PROTEIN and BRD2 HGNC evolved to manipulate the transcriptional host response during SARS-CoV-2 infection MESHD. Together, our results pinpoint BRD2 HGNC as a potent and essential regulator of the host response to SARS-CoV-2 infection MESHD and highlight the potential of BRD2 HGNC as a novel therapeutic target for COVID-19 MESHD.

    Ultrasensitive RNA biosensors for SARS-CoV-2 detection in a simple color and luminescence assay

    Authors: Anirudh Chakravarthy; Anirudh K N; Geen George; Shyamsundar Ranganathan; Nishan Shettigar; Suchitta U; Dasaradhi Palakodeti; Akash Gulyani; Arati Ramesh

    doi:10.1101/2021.01.08.21249426 Date: 2021-01-08 Source: medRxiv

    The COVID-19 pandemic MESHD underlines the need for versatile diagnostic strategies. Here, we have designed and developed toehold RNA-based sensors for direct and ultrasensitive SARS-CoV-2 RNA detection. In our assay, isothermal amplification of a fragment of SARS-CoV-2 RNA coupled with activation of our biosensors leads to a conformational switch in the sensor. This leads to translation of a reporter- protein e PROTEIN.g. LacZ or Nano-lantern that is easily detected using color/luminescence. This response can be visualized by the human eye, or a simple cell phone camera as well as quantified using a spectrophotometer/luminometer. By optimizing RNA-amplification and biosensor-design, we have generated a highly-sensitive diagnostic assay; with sensitivity down to attomolar (100 copies of) SARS-CoV-2 RNA. Finally, this PHAsed NASBA-Translation Optical Method (PHANTOM) efficiently detects the presence of viral RNA in human patient samples, with clear distinction from samples designated negative for the virus. The biosensor response correlates well with Ct values from RT-qPCR tests and thus presents a powerful and easily accessible strategy for detecting Covid infection.

    Sequencing of SARS CoV2 in local transmission cases through oxford nanopore MinION platform from Karachi Pakistan

    Authors: Samina Naz Mukry; Shariq Ahmed; Ali Raza Bukhari; Aneeta Shahni; Gul Sufaida; Arshi Naz; Tahir Sultan Shamsi; Vineet D Menachery; Scott D Weaver; Philip R Dormitzer; Pei-Yong Shi

    doi:10.1101/2021.01.07.425705 Date: 2021-01-07 Source: bioRxiv

    The first case of severe acute respiratory syndrome MESHD 2 (SARS CoV2) was imported to Pakistan in February 2020 since then 10,258 deaths have been witnessed. The virus has been mutating and local transmission cases from different countries vary due to host dependent viral adaptation. Many distinct clusters of variant SARS CoV2 have been defined globally. In this study, the epidemiology of SARS CoV2 was studied and locally transmitted SARS CoV2 isolates from Karachi were sequenced to compared and identify any possible variants.The real time PCR was performed on nasopharyngeal specimen to confirm SARSCoV2 with Orf 1ab and E gene PROTEIN as targets. The viral sequencing was performed through oxford nanopore technology MinION platform. Isolates from first and second wave of COVID-19 MESHD outbreak in Karachi were compared. The overall positivity rate for PCR was 26.24% with highest number of positive cases in June. Approximately, 37.45% PCR positive subjects aged between 19-40 years. All the isolates belonged to GH clade and shared missense mutation D614G in spike protein PROTEIN linked to increased transmission rate worldwide. Another spike protein PROTEIN mutation A222V coexisted with D614G in the virus from second wave of COVID-19 MESHD. Based on the present findings it is suggested that the locally transmitted virus from Karachi vary from those reported from other parts of Pakistan. Slight variability was also observed between viruses from first and second wave. Variability in any potential vaccine target may result in failed trials therefore information on any local viral variants is always useful for effective vaccine design and/or selection. Authors summaryDespite precautionary measures the COVID-19 pandemic MESHD is causing deaths all over the world. The continuous mutations in viral genome is making it difficult to design vaccines. Variability in genome is host dependent and data sharing has revealed that variant for different geographical locations may harbor different mutations. Keeping this in mind the current study was focused on the epidemiology of SARS CoV2 in symptomatic and asymptomatic COVID -19 suspected cases with impact of age and gender. The locally transmitted SARS CoV2 isolates from Karachi were sequenced to compared and identify any possible variants. The sequenced viral genome varied from the already submitted sequences from Pakistan thereby confirming that slightly different viruses were causing infections during different time periods in Karachi. All belonged to GH clade with D614G, P323L and Q57H mutations. The virus from second wave had A222V mutation making it more different. This information can be useful in selecting or designing a vaccine.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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