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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinE (102)

ProteinS (28)

ProteinN (24)

ComplexRdRp (13)

ProteinM (12)


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SARS-CoV-2 Proteins
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    Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry MESHD

    Authors: Shiyou Zhu; Ying Liu; Zhuo Zhou; Zhiying Zhang; Xia Xiao; Zhiheng Liu; Ang Chen; Xiaojing Dong; Feng Tian; Shihua Chen; Yiyuan Xu; Chunhui Wang; Qiheng Li; Xuran Niu; Qian Pan; Shuo Du; Junyu Xiao; Jianwei Wang; Wensheng Wei

    doi:10.1101/2021.04.08.438924 Date: 2021-04-09 Source: bioRxiv

    The ongoing pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects MESHD a variety of tissues where the known receptor ACE2 HGNC is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection MESHD. In addition to known host proteins, i.e PROTEIN. ACE2 HGNC, TMPRSS2 HGNC, and NRP1 HGNC, we identified multiple host components, among which LDLRAD3 HGNC, TMEM30A HGNC, and CLEC4G HGNC were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain ( NTD HGNC). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 HGNC and CLEC4G HGNC mediate SARS-CoV-2 entry MESHD and infection in a fashion independent of ACE2 HGNC. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19 MESHD.

    Interactions of SARS-CoV-2 envelope protein PROTEIN with amilorides correlate with antiviral activity

    Authors: Sang Ho Park; Haley Siddiqi; Daniela Castro; Anna De Angelis; Aaron L. Oom; Charlotte Stoneham; Mary Lewinski; Alex Clark; Ben Croker; Aaron Carlin; John Guatelli; Stanley J. Opella

    doi:10.1101/2021.04.06.438579 Date: 2021-04-06 Source: bioRxiv

    SARS-CoV-2 is the novel coronavirus that is the causative agent of COVID-19 MESHD, a sometimes-lethal respiratory infection MESHD responsible for a world-wide pandemic. The envelope (E) protein PROTEIN, one of four structural proteins encoded in the viral genome, is a 75-residue integral membrane protein whose transmembrane domain exhibits ion channel activity and whose cytoplasmic domain participates in protein-protein interactions. These activities contribute to several aspects of the viral replication-cycle, including virion assembly, budding, release, and pathogenesis. Here, we describe the structure and dynamics of full-length SARS-CoV-2 E protein PROTEIN in hexadecylphosphocholine micelles by NMR spectroscopy. We also characterized its interactions with four putative ion channel inhibitors. The chemical shift index and dipolar wave plots establish that E protein PROTEIN consists of a long transmembrane helix (residues 8-43) and a short cytoplasmic helix (residues 53-60) connected by a complex linker that exhibits some internal mobility. The conformations of the N-terminal transmembrane domain and the C-terminal cytoplasmic domain are unaffected by truncation from the intact protein. The chemical shift perturbations of E protein PROTEIN spectra induced by the addition of the inhibitors demonstrate that the N-terminal region (residues 6-18) is the principal binding site. The binding affinity of the inhibitors to E protein PROTEIN in micelles correlates with their antiviral potency in Vero E6 cells: HMA {approx} EIPA > DMA >> Amiloride, suggesting that bulky hydrophobic groups in the 5 position of the amiloride pyrazine ring play essential roles in binding to E protein PROTEIN and in antiviral activity. An N15A mutation increased the production of virus-like particles, induced significant chemical shift changes from residues in the inhibitor binding site, and abolished HMA binding, suggesting that Asn15 plays a key role in maintaining the protein conformation near the binding site. These studies provide the foundation for complete structure determination of E protein PROTEIN and for structure-based drug discovery targeting this protein. Author SummaryThe novel coronavirus SARS-CoV-2, the causative agent of the world-wide pandemic of COVID-19 MESHD, has become one of the greatest threats to human health. While rapid progress has been made in the development of vaccines, drug discovery has lagged, partly due to the lack of atomic-resolution structures of the free and drug-bound forms of the viral proteins. The SARS-CoV-2 envelope (E) protein PROTEIN, with its multiple activities that contribute to viral replication, is widely regarded as a potential target for COVID-19 MESHD treatment. As structural information is essential for drug discovery, we established an efficient sample preparation system for biochemical and structural studies of intact full-length SARS-CoV-2 E protein PROTEIN and characterized its structure and dynamics. We also characterized the interactions of amilorides with specific E protein PROTEIN residues and correlated this with their antiviral activity during viral replication. The binding affinity of the amilorides to E protein PROTEIN correlated with their antiviral potency, suggesting that E protein PROTEIN is indeed the likely target of their antiviral activity. We found that residue asparagine15 plays an important role in maintaining the conformation of the amiloride binding site, providing molecular guidance for the design of inhibitors targeting E protein PROTEIN.

    Monitoring occurrence of SARS-CoV-2 in school populations: a wastewater-based approach

    Authors: Victor Castro Gutierrez; Francis Hassard; Milan Vu; Rodrigo Leitao; Beata Burczynska; Dirk Wildeboer; Isobel Stanton; Shadi Rahimzadeh; Gianluca Baio; Hemda Garelick; Jan Hofman; Barbara Kasprzyk-Hordern; Rachel Kwiatkowska; Azeem Majeed; Sally Priest; Jasmine Grimsley; Lian Lundy; Andrew C Singer; Mariachiara Di Cesare

    doi:10.1101/2021.03.25.21254231 Date: 2021-03-26 Source: medRxiv

    Clinical testing of children in schools is challenging, with economic implications limiting its frequent use as a monitoring tool of the risks assumed by children and staff during the COVID-19 pandemic MESHD. Here, a wastewater based epidemiology approach has been used to monitor 16 schools (10 primary, 5 secondary and 1 post-16 and further education for a total of 17 sites) in England. A total of 296 samples over 9 weeks have been analysed for N1 and E genes PROTEIN using qPCR methods. Of the samples returned, 47.3% were positive for one or both genes with a frequency of detection in line with the respective community. WBE offers a promising low cost, non-invasive approach for supplementing clinical testing and can offer longitudinal insights that are impractical with traditional clinical testing.

    S-acylation controls SARS-Cov-2 membrane lipid organization and enhances infectivity MESHD

    Authors: Francisco Sarmento Mesquita; Laurence Abrami; Oksana Sergeeva; Priscilla Turelli; Beatrice Kunz; Charlene Raclot; Jonathan Paz Montoya; Luciano Abriata; Matteo Dal Peraro; Didier Trono; F. Gisou van der Goot

    doi:10.1101/2021.03.14.435299 Date: 2021-03-15 Source: bioRxiv

    SARS-CoV-2 virions are surrounded by a lipid bilayer which contains membrane proteins such as Spike PROTEIN, responsible for target-cell binding and virus fusion, the envelope protein E PROTEIN and the accessory protein Orf3a PROTEIN. Here, we show that during SARS-CoV-2 infection MESHD, all three proteins become lipid modified, through action of the S- acyltransferase ZDHHC20 HGNC. Particularly striking is the rapid acylation of Spike on 10 cytosolic cysteines within the ER and Golgi. Using a combination of computational, lipidomics and biochemical approaches, we show that this massive lipidation controls Spike biogenesis and degradation, and drives the formation of localized ordered cholesterol and sphingolipid rich lipid nanodomains, in the early Golgi where viral budding occurs. ZDHHC20 HGNC-mediated acylation allows the formation of viruses with enhanced fusion capacity and overall infectivity. Our study points towards S-acylating enzymes and lipid biosynthesis enzymes as novel therapeutic anti-viral targets.

    Long-read sequencing of SARS-CoV-2 reveals novel transcripts and a diverse complex transcriptome landscape.

    Authors: Jennifer Li-Pook-Than; Selene Banuelos; Alexander Honkala; Malaya K Sahoo; Benjamin A Pinsky; Michael P Snyder

    doi:10.1101/2021.03.05.434150 Date: 2021-03-06 Source: bioRxiv

    Severe Acute Respiratory Syndrome Coronavirus 2 MESHD, SARS-CoV-2 ( COVID-19 MESHD), is a positive single-stranded RNA virus with a 30 kb genome that is responsible for the current pandemic. To date, the genomes of global COVID-19 MESHD variants have been primarily characterized via short-read sequencing methods. Here, we devised a long-read RNA (IsoSeq) sequencing approach to characterize the COVID-19 MESHD transcript landscape and expression of its [~]27 coding regions. Our analysis identified novel COVID-19 MESHD transcripts including a) a short [~]65-70 nt 5-UTR fused to various downstream ORFs encoding accessory proteins such as the envelope PROTEIN, ORF 8, and ORF 9 HGNC ( nucleocapsid) proteins PROTEIN, that are relatively highly expressed, b) novel SNVs that are differentially expressed, whereby a subset are suggestive of partial RNA editing events, and c) SNVs at functional sites, whereby at least one is associated with a differentially expressed spike protein PROTEIN isoform. These previously uncharacterized COVID-19 MESHD isoforms, expressed genes, and gene variants were corroborated using ddPCR. Understanding this transcriptional complexity may help provide insight into the biology and pathogenicity of SARS-CoV-2 compared to other coronaviruses.

    Redesigning SARS-CoV-2 clinical RT-qPCR assays for wastewater RT-ddPCR

    Authors: Raul Alexander Gonzalez; Allison Larson; Hannah Thompson; Errin Carter; Xavier Fernandez Cassi

    doi:10.1101/2021.03.02.21252754 Date: 2021-03-05 Source: medRxiv

    COVID-19 MESHD wastewater surveillance has gained widespread acceptance to monitor community infection trends. Wastewater samples primarily differ from clinical samples by having low viral concentrations due to dilution, and high levels of PCR inhibitors. Therefore, wastewater samples should have appropriately designed and optimized molecular assays. Digital PCR has proven to be more sensitive and resilient to matrix inhibition. However, most SARS-CoV-2 assays being used have been designed for clinical use on RT-qPCR instruments, then adopted to digital PCR platforms. But it is unknown whether clinical RT-qPCR assays are adequate to use on digital PCR platforms. Here we designed an N- and E- gene PROTEIN multiplex (ddCoV_N and ddCoV_E) specifically for RT-ddPCR and benchmarked them against the nCoV_N2 and E_Sarbeco assays. ddCoV_N and ddCoV_E have equivalent limits of detections and samples concentrations to NCoV_N2 and E_Sarbeco but showed improved signal-to-noise ratios that eased interpretation and ability to multiplex. From GISAID downloaded unique sequences analyzed, 2.12% and 0.83% present a mismatch or would not be detected by the used primer/probe combination for the ddCoV_N and ddCoV_E, respectively.

    Evaluation of a Sample Pooling Strategy for Sars-cov-2 Using Real Time PCR

    Authors: Annet M Nankya; Luke Nyakarahuka; Stephen Balinandi; John Kayiwa; Julius Lutwama; Andrew Tamale; Joseph M Kungu

    doi:10.21203/rs.3.rs-290291/v1 Date: 2021-03-02 Source: ResearchSquare

    Back ground: Corona Virus Disease MESHD 2019 (COVID 19) in Uganda was first reported in a male traveler from Dubai on 21st March, 2020 shortly after WHO had announced the condition as a global pandemic. Timely laboratory diagnosis of COVID -19 for all samples from both symptomatic and asymptomatic patients was observed as key in containing the pandemic and breaking the chain of transmission. However, there was a challenge of limited resources required for testing SARS-COV-2 in low and middle income countries. To mitigate this, a study was conducted to evaluate a sample pooling strategy for COVI-19 using real time PCR. The cost implication and the turn around time of pooled sample testing versus individual sample testing were also compared.Methods: In this study, 1260 randomly selected samples submitted to Uganda Virus Research Institute for analysis were batched in pools of 5, 10, and 15. The pools were then extracted using a Qiagen kit. Both individual and pooled RNA were screened for the SARS-COV-2 E gene PROTEIN using a Berlin kit. Results: Out of 1260 samples tested, 21 pools were positive in pools of 5 samples, 16 were positive in pools of 10 and 14 were positive in pools of 15 samples. The study also revealed that the pooling strategy helps to save a lot on resources, time and expands diagnostic capabilities without affecting the sensitivity of the test in areas with low SARS-COV-2 prevalence.Conclusion: This study demonstrated that the pooling strategy for COVID-19 MESHD reduced on the turnaround time and there was a substantial increase in the overall testing capacity with limited resources as compared to individual testing.

    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.

    Structural Basis for SARS-CoV-2 Envelope Protein PROTEIN in Recognition of Human Cell Junction Protein PALS1

    Authors: Jin Chai; Yuanheng Cai; Changxu Pang; Liguo Wang; Sean McSweeney; John Shanklin; Qun Liu

    doi:10.1101/2021.02.22.432373 Date: 2021-02-23 Source: bioRxiv

    The COVID-19 pandemic MESHD caused by the SARS-CoV-2 virus has created a global health and economic emergency. SARS-CoV-2 viruses hijack human proteins to promote their spread and virulence including the interactions involving the viral envelope (E) protein PROTEIN and human proteins. To understand the structural basis for SARS-CoV-2 viral-host recognition, we used cryo-electron microscopy to determine a structure for the human cell junction protein PALS1 HGNC and SARS-CoV-2 E protein PROTEIN complex. The structure shows that the E protein PROTEIN C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains in PALS1 HGNC. Our structural analysis provides an explanation for the observation that the viral E protein PROTEIN recruits PALS1 HGNC from lung epithelial cell junctions resulting in vascular leakage, lung damage MESHD, viral spread, and virulence. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1 HGNC-E interactions to reduce the E-mediated damage to vascular structures.

    Harnessing recombinase polymerase amplification for rapid detection of SARS-CoV-2 in resource-limited settings

    Authors: Dounia Cherkaoui; Da Huang; Benjamin Miller; Rachel A McKendry

    doi:10.1101/2021.02.17.21251732 Date: 2021-02-19 Source: medRxiv

    The COVID-19 pandemic MESHD has challenged testing capacity worldwide. The mass testing needed to stop the spread of the virus requires new molecular diagnostic tests that are faster and with reduced equipment requirement, but as sensitive as the current gold standard protocols based on polymerase chain reaction. We developed a fast (25-35 minutes) molecular test using reverse transcription recombinase polymerase amplification for simultaneous detection of two conserved regions of the virus, targeting the E and RdRP PROTEIN genes. The diagnostic platform offers two complementary detection methods: real-time fluorescence or visual dipstick. The analytical sensitivity of the test by real-time fluorescence was 9.5 (95% CI: 7.0-18) RNA copies per reaction for the E gene PROTEIN and 17 (95% CI: 11-93) RNA copies per reaction for the RdRP PROTEIN gene. The analytical sensitivity for the dipstick readout was 130 (95% CI: 82-500) RNA copies per reaction. The assay showed high specificity with both detection methods when tested against common seasonal coronaviruses, SARS-CoV and MERS-CoV MESHD model samples. The dipstick readout demonstrated potential for point-of-care testing, with simple or equipment-free incubation methods and a user-friendly prototype smartphone application was proposed with data capture and connectivity. This ultrasensitive molecular test offers valuable advantages with a swift time-to-result and it requires minimal laboratory equipment compared to current gold standard assays. These features render this diagnostic platform more suitable for decentralised molecular testing.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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