preVIEW: COVID-19

Corpus overview

Overview

MeSH Disease

COVID-19 (28)

Severe Acute Respiratory Syndrome (15)

Coronavirus Infections (5)

Death (3)

Virus Diseases (2)


HGNC Genes

angiotensin I converting enzyme 2 (5)

endogenous retrovirus group K member 6 (2)

transmembrane serine protease 2 (2)

helicase for meiosis 1 (2)

TNF receptor associated factor 5 (1)


SARS-CoV-2 proteins

ProteinS (39)

ProteinE (39)

ProteinN (13)

ProteinM (12)

NSP5 (3)


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    Altered O-glycosylation Level of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN Protein by Host O-glycosyltransferase Strengthens Its Trimeric Structure

    Authors: Zhijue Xu; Xin Ku; Jiaqi Tian; Han Zhang; Jingli Hou; Can Zhang; Jingjing Shi; Yang Li; Hiroyuki Kaji; Sheng-ce Tao; Atsushi Kuno; Wei Yan; Lin-Tai Da; Yan Zhang

    doi:10.1101/2021.04.06.438614 Date: 2021-04-06 Source: bioRxiv

    The trimeric spike protein (S PROTEIN) mediates host-cell entry and membrane fusion of SARS-CoV-2. S protein PROTEIN is highly glycosylated, whereas its O-glycosylation is still poorly understood. Herein, we site-specifically examine the O-glycosylation of S protein PROTEIN through a mass spectrometric approach with HCD MESHD-triggered-ETD model. We identify 15 high-confidence O-glycosites and at least 10 distinct O-glycan structures on S protein PROTEIN. Peptide microarray assays prove that human ppGalNAc-T6 actively participates in O-glycosylation of S protein PROTEIN. Importantly, the upregulation of ppGalNAc-T6 expression can profoundly enhance the O-glycosylation level by generating new O-glycosites and increasing both O-glycan heterogeneity and intensities. Further molecular dynamics simulations reveal that the O-glycosylation on the protomer-interface regions, which are mainly modified by ppGalNAc-T6, can potentially stabilize the trimeric S protein PROTEIN structure. Our work provides deep molecular insights of how viral infection harnesses the host O-glycosyltransferases MESHD to dynamically regulate the O-glycosylation level of the viral envelope protein PROTEIN responsible for membrane fusion.

    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.

    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.

    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.

    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.

    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.

    Surface proteins of SARS-CoV-2 drive airway epithelial cells to induce interferon-dependent inflammation MESHD

    Authors: Gautam Anand; Alexandra M Perry; Celeste L Cummings; Emma St. Raymond; Regina A Clemens; Ashley L Steed

    doi:10.1101/2020.12.14.422710 Date: 2020-12-14 Source: bioRxiv

    SARS-CoV-2, the virus that has caused the COVID-19 pandemic MESHD, robustly activates the host immune system in critically ill MESHD patients. Understanding how the virus engages the immune system will facilitate the development of needed therapeutic strategies. Here we demonstrate both in vitro and in vivo that the SARS-CoV-2 surface proteins Spike (S PROTEIN) and Envelope (E) activate the key immune signaling interferon (IFN) pathway in both immune and epithelial cells independent of viral infection MESHD and replication. These proteins induce reactive oxidative species generation and increases in human and murine specific IFN-responsive cytokines and chemokines, similar to their upregulation in critically ill COVID-19 MESHD patients. Induction of IFN signaling is dependent on canonical but discrepant inflammatory signaling mediators as the activation induced by S is dependent on IRF3 HGNC, TBK1 HGNC, and MYD88 HGNC while that of E is largely MYD88 HGNC independent. Furthermore, these viral surface proteins, specifically E, induced peribronchial inflammation MESHD and pulmonary vasculitis MESHD in a mouse model. Finally we show that the organized inflammatory infiltrates are dependent on type I IFN signaling, specifically in lung epithelial cells. These findings underscore the role of SARS-CoV-2 surface proteins, particularly the understudied E protein PROTEIN, in driving cell specific inflammation MESHD and their potential for therapeutic intervention. Author SummarySARS-CoV-2 robustly activates widespread inflammation MESHD, but we do not understand mechanistically how the virus engages the immune system. This knowledge will facilitate the development of critically needed therapeutic strategies to promote beneficial immune responses will dampening harmful inflammation MESHD. Here we demonstrate that SARS-CoV-2 surface proteins spike PROTEIN and envelope alone activated innate cell function and the interferon signaling pathway. This activation occurred in both immune and epithelial cells, and mechanistic studies demonstrated dependence on known key inflammatory signaling mediators, IRF3 HGNC, TBK1 HGNC, and MYD88 HGNC. In animal studies, we showed that these viral surface proteins induce epithelial cell IFN-dependent lung pathology, reminiscent to acute COVID-19 MESHD pulmonary infection MESHD. These findings underscore the need for further investigation into the role of SARS-CoV-2 surface proteins, particularly the understudied E protein PROTEIN, in driving cell specific inflammation MESHD.

    Binding of SARS-CoV-2 spike PROTEIN protein to ACE2 HGNC is disabled by thiol-based drugs; evidence from in vitro SARS-CoV-2 infection MESHD studies.

    Authors: Kritika Khanna; Wilfred Raymond; Annabelle R Charbit; Jing Jin; Irina Gitlin; Monica Tang; Hannah S Sperber; Sergej Franz; Satish Pillai; Graham Simmons; John V Fahy; Suparerk Borwornpinyo; Arunee Thitithanyanont; Suradej Hongeng; Casey Barton Behravesh; Rebecca Fischer; Gabriel L Hamer; Marion Frankenberger; Lorenz Nowak; Katharina Heinig; Ina Koch; Mircea G Stoleriu; Anne Hilgendorff; Juergen Behr; Andreas Pichlmair; Benjamin Schubert; Fabian J Theis; Dirk H Busch; Herbert B Schiller; Kilian Schober; Evangelos J Giamarellos-Bourboulis; Timothy E Sweeney

    doi:10.1101/2020.12.08.415505 Date: 2020-12-08 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), and the SARS-CoV-2 spike PROTEIN protein is an envelope PROTEIN glycoprotein that binds angiotensin converting enzyme 2 as an entry receptor. The capacity of enveloped viruses to infect host MESHD cells depends on a precise thiol/disulfide balance in their surface glycoprotein complexes. To determine if cystines MESHD in the SARS-CoV-2 spike PROTEIN protein maintain a native binding interface that can be disrupted by drugs that cleave cystines, we tested if thiol-based drugs have efficacy in receptor binding and cell infection assays. We found that thiol-based drugs, cysteamine and WR-1065 (the active metabolite of amifostine) in particular, decrease binding of SARS-CoV-2 spike PROTEIN protein to its receptor, decrease the entry efficiency of SARS-CoV-2 spike PROTEIN pseudotyped virus, and inhibit SARS-CoV-2 live virus infection MESHD. Our findings uncover a vulnerability of SARS-CoV-2 to thiol-based drugs and provide rationale to test thiol-based drugs, especially cysteamine and amifostine, as novel treatments for COVID-19 MESHD. One Sentence SummaryThiol-based drugs decrease binding of SARS-CoV-2 spike PROTEIN protein to its receptor and inhibit SARS-CoV-2 cell entry.

    Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination

    Authors: Shang-Jui Tsai; Chenxu Guo; Nadia A Atai; Stephen J Gould; Emma S Child; Rhodri M L Morgan; Alan Armstrong; David J Mann; Sheng Cui; Paulo Souza-Fonseca Guimaraes; Lucia Noronha; Timothy McCulloch; Gustavo Rodrigues Rossi; Caroline Cooper; Benjamin Tang; Kirsty Short; Melissa J Davis; Fernando Souza-Fonseca Guimaraes; Gabrielle T Belz; Ken O'Byrne

    doi:10.1101/2020.11.06.371419 Date: 2020-11-06 Source: bioRxiv

    Background: In less than a year from its zoonotic entry into the human population, SARS-CoV-2 has infected more than 45 million people, caused 1.2 million deaths, and induced widespread societal disruption MESHD. Leading SARS-CoV-2 vaccine candidates immunize with the viral spike protein PROTEIN delivered on viral vectors, encoded by injected mRNAs, or as purified protein. Here we describe a different approach to SARS-CoV-2 vaccine development that uses exosomes to deliver mRNAs that encode antigens from multiple SARS-CoV-2 structural proteins. Approach: Exosomes were purified and loaded with mRNAs designed to express (i) an artificial fusion protein, LSNME, that contains portions of the viral spike, nucleocapsid, membrane, and envelope proteins PROTEIN, and (ii) a functional form of spike. The resulting combinatorial vaccine, LSNME/SW1, was injected into thirteen weeks-old, male C57BL/6J mice, followed by interrogation of humoral and cellular immune responses to the SARS-CoV-2 nucleocapsid and spike proteins PROTEIN, as well as hematological and histological analysis to interrogate animals for possible adverse effects. Results: Immunized mice developed CD4+, and CD8+ T-cell reactivities that respond to both the SARS-CoV-2 nucelocapsid protein and the SARS-CoV-2 spike PROTEIN protein. These responses were apparent nearly two months after the conclusion of vaccination, as expected for a durable response to vaccination. In addition, the spike-reactive CD4+ T-cells response was associated with elevated expression of interferon gamma, indicative of a Th1 response, and a lesser induction of interleukin 4, a Th2-associated cytokine. Vaccinated mice showed no sign of altered growth, injection-site hypersensitivity MESHD, change in white blood cell profiles, or alterations in organ morphology. Consistent with these results, we also detected moderate but sustained anti-nucleocapsid and anti-spike antibodies in the plasma of vaccinated animals. Conclusion: Taken together, these results validate the use of exosomes for delivering functional mRNAs into target cells in vitro and in vivo, and more specifically, establish that the LSNME/SW1 vaccine induced broad immunity to multiple SARS-CoV-2 proteins.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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