Corpus overview


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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (312)

ProteinN (25)

NSP5 (13)

ORF1ab (8)

ORF8 (5)


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SARS-CoV-2 Proteins
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    The multi-epitope vaccine prediction to combat Pandemic SARS-CoV-2, an immunoinformatic approach

    Authors: K. M. Kaderi Kibria; Md. Shaid bin Islam; Hedayet Ullah; Mojnu Miah

    doi:10.21203/rs.3.rs-21853/v1 Date: 2020-04-07 Source: ResearchSquare

    Novel coronavirus (SARS-CoV-2) leads to coronavirus disease MESHD 19 ( COVID-19 MESHD) recently declared as a pandemic for its outbreak within almost 190 countries worldwide. No effective drugs and/or vaccines authenticated against this rapidly spreading virus till now. This study aims to establish an efficient multi-epitope vaccine that could elicit both T-cell and B-cell responses sufficient to recognize confirmed surface proteins of the virus. The sequences of the viral surface proteins, e PROTEIN.g. envelope protein (E PROTEIN), membrane glycoprotein (M PROTEIN), and S1 and S2 domain of spike surface glycoprotein (S PROTEIN) collected from the NCBI database. We adopted an immunoinformatic strategy to identify the immunogenic region of the proteins and assessed their affinity with MHC class-I and MHC class-II by various bioinformatics tools. Top epitopes have been selected and assessed for population coverage and conservancy among 180 SARS-CoV-2 genomes. Along with the above analyses, and results of Antigenicity, Allergenicity, and transmembrane location prediction, we selected top epitopes from these four proteins. The epitopes were assembled by the AAY linker to form a multi-epitope vaccine is 70 aa long, can be synthesized commercially. This should be processed by Antigen-presenting cells; consequently, the surface proteins might be recognized by the helper and cytotoxic T-cells as well as by B-cells. We also assessed the structural and various physicochemical properties of the novel chimeric peptide for its suitability as a multi-epitope vaccine. This in-silico study leads to a rationally designed potential vaccine candidate that could be assessed by wet-lab experiments driving towards efficient combat of the novel coronavirus outbreak.

    The genomic recombination events may reveal the evolution of coronavirus and the origination of 2019-nCoV

    Authors: Zhenglin Zhu; Kaiwen Meng; Geng Meng

    doi:10.21203/rs.3.rs-21488/v1 Date: 2020-04-05 Source: ResearchSquare

    To trace the evolution of coronavirus and reveal the possible origination of the novel pneumonia coronavirus MESHD (2019-nCoV), we collected and thoroughly analyzed 2966 publicly available coronavirus genomes, including 182 2019-nCoVs strains. We observed 3 independent recombination events with statistical significance between some isolates from bats and pangolins. In consistence with previous records, we also detected the putative recombination between Bat-CoV-RaTG13 and Pangolin-CoV-2019 covering the receptor bind domain (RBD) of the spike glycoprotein PROTEIN ( S protein PROTEIN), which may lead to the origination of 2019-nCoV. Population genetic analyses give estimations indicating that the recombinant region around RBD is possibly undergoing directional evolution. This may result to the adaption of the virus to be infectious in hosts. Not surprisingly, we find that the S protein PROTEIN of coronavirus keeps high diversity among bat isolates, which may provide a genetic pool for the origination of 2019-nCoV.

    Amantadine disrupts lysosomal gene expression; potential therapy for COVID19 MESHD

    Authors: Sandra Smieszek; Bart Przychodzen; Mihael H Polymeropoulos

    doi:10.1101/2020.04.05.026187 Date: 2020-04-05 Source: bioRxiv

    SARS-coronavirus MESHD 2 is the causal agent of the COVID-19 MESHD outbreak. SARS-Cov-2 entry into a cell is dependent upon binding of the viral spike (S) protein PROTEIN to cellular receptor and on cleavage of the spike protein PROTEIN by the host cell proteases such as Cathepsin L HGNC and Cathepsin B HGNC. CTSL HGNC/B are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes. CTSL HGNC disruption offers potential for CoVID-19 MESHD therapies. The mechanisms of disruption include: decreasing expression of CTSL HGNC, direct inhibition of CTSL HGNC activity and affecting the conditions of CTSL HGNC environment (increase pH in lysosomes). We have conducted a high throughput drug screen gene expression analysis to identify compounds that would downregulate the expression of CTSL HGNC/ CTSB HGNC. One of the top significant results shown to downregulate the expression of the CTSL HGNC gene is Amantadine. Amantadine was approved by the US Food and Drug Administration in 1968 as a prophylactic agent for influenza and later for Parkinsons disease. It is available as a generic drug.. Amantadine in addition to downregulating CTSL HGNC appears to further disrupt lysosomal pathway, hence interfering with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL HGNC functional environment. We hypothesize that Amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies will be needed to examine the therapeutic utility of amantadine in COVID-19 MESHD infection.

    LY6E HGNC Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2

    Authors: Xuesen Zhao; Shuangli Zheng; Danying Chen; Mei Zheng; Xinglin Li; Guoli Li; Hanxin Lin; Jinhong Chang; Hui Zeng; Ju-Tao Guo

    doi:10.1101/2020.04.02.021469 Date: 2020-04-05 Source: bioRxiv

    C3A HGNC is a sub-clone of human hepatoblastoma MESHD HepG2 cell line with the strong contact inhibition of growth. We fortuitously found that C3A HGNC was more susceptible to human coronavirus HCoV-OC43 infection MESHD than HepG2, which was attributed to the increased efficiency of virus entry into C3A HGNC cells. In an effort to search for the host cellular protein(s PROTEIN) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection MESHD, we found that ADAP2 HGNC, GILT HGNC and LY6E HGNC, three cellular proteins with known activity of interfering virus entry, expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E HGNC, but not GILT HGNC or ADAP2 HGNC, in HEK 293 cells inhibited the entry of HCoV-OC43. While overexpression of LY6E HGNC in C3A HGNC and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E HGNC expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection MESHD. Moreover, we found that LY6E HGNC also efficiently restricted the entry mediated by the envelope spike proteins PROTEIN of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFITM3 restriction of human coronavirus entry, but did not compromise the effect of LY6E HGNC on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E HGNC is a critical antiviral immune effector that controls CoV infection MESHD and pathogenesis via a distinct mechanism. ImportanceVirus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control by host innate and adaptive immune responses. In the last decade, several interferon inducible cellular proteins, including IFITMs, GILT HGNC, ADAP2 HGNC, 25CH and LY6E HGNC, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E HGNC was recently identified as host factors to facilitate the entry of several human pathogenic viruses, including human immunodeficiency virus, influenza A virus and yellow fever virus. Identification of LY6E HGNC as a potent restriction factor of coronaviruses expands the biological function of LY6E HGNC and sheds new light on the immunopathogenesis of human coronavirus infection.

    Prediction of repurposed drugs for treating lung injury in COVID-19 MESHD

    Authors: Bing He; Lana Garmire

    id:2003.14333v2 Date: 2020-03-30 Source: arXiv

    Coronavirus disease MESHD ( COVID-19 MESHD) is an infectious disease MESHD discovered in 2019 and currently in outbreak across the world. Lung injury MESHD with severe respiratory failure MESHD is the leading cause of death MESHD in COVID-19 MESHD, brought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 MESHD induced lung injury MESHD and acute respiratory failure MESHD. Inhibition of Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) caused by spike protein PROTEIN of SARS-CoV-2 is the most plausible mechanism of lung injury MESHD in COVID-19 MESHD. We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries MESHD in COVID-19 MESHD, based on their abilities to reverse the gene expression patterns in HCC515 cells treated with ACE2 HGNC inhibitor and in human COVID-19 MESHD patient lung tissues. Further bioinformatics analysis shows that twelve significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 HGNC inhibitor and human COVID-19 MESHD patient lung tissues, including signaling pathways known to be associated with lung injury MESHD such as TNF signaling, MAPK signaling and Chemokine signaling pathways. All these twelve pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA HGNC, RAC2 HGNC, FAS, CDC42 HGNC have reduced expression. CGP-60474 shares eleven of twelve pathways with COL-3 with common target genes such as RHOA HGNC. It also uniquely targets genes related to lung injury MESHD, such as CALR HGNC and MMP14 HGNC. In summary, this study shows that ACE2 HGNC inhibition is likely part of the mechanisms leading to lung injury MESHD in COVID-19 MESHD, and that compounds such as COL-3 and CGP-60474 have the potential as repurposed drugs for its treatment.

    Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies

    Authors: Daniel Wrapp; Dorien De Vlieger; Kizzmekia S Corbett; Gretel M Torres; Wander Van Breedam; Kenny Roose; Loes van Schie; - VIB-CMB COVID-19 Response Team; Markus Hoffmann; Stefan Pöhlmann; Barney S Graham; Nico Callewaert; Bert Schepens; Xavier Saelens; Jason S McLellan

    doi:10.1101/2020.03.26.010165 Date: 2020-03-28 Source: bioRxiv

    The pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) MESHD, severe acute respiratory syndrome coronavirus (SARS-CoV-1) MESHD and COVID-19 MESHD coronavirus (SARS-CoV-2) have all emerged into the human population with devastating consequences. These viruses make use of a large envelope protein PROTEIN called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins PROTEIN play, they represent a vulnerable target for the development of therapeutics to combat these highly pathogenic coronaviruses. Here, we describe the isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs are capable of potently neutralizing MERS-CoV MESHD or SARS-CoV-1 S pseudotyped viruses. The crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs block MESHD receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S MESHD, and demonstrate that this cross-reactive VHH is capable of neutralizing SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

    Electrical probing of COVID-19 MESHD spike protein PROTEIN receptor binding domain via a graphene field-effect transistor

    Authors: Xiaoyan Zhang; Qige Qi; Qiushi Jing; Shen Ao; Zhihong Zhang; Mingchao Ding; Muhong Wu; Kaihui Liu; Weipeng Wang; Yunhan Ling; Zhengjun Zhang; Wangyang Fu

    id:2003.12529v1 Date: 2020-03-27 Source: arXiv

    Here, in an effort towards facile and fast screening/diagnosis of novel coronavirus disease 2019 MESHD ( COVID-19 MESHD), we combined the unprecedently sensitive graphene field-effect transistor (Gr-FET) with highly selective antibody-antigen interaction to develop a coronavirus immunosensor MESHD. The Gr-FET immunosensors can rapidly identify (about 2 mins) and accurately capture the COVID-19 MESHD spike protein S1 PROTEIN (which contains a receptor binding domain, RBD) at a limit of detection down to 0.2 pM, in a real-time and label-free manner. Further results ensure that the Gr-FET immunosensors can be promisingly applied to screen for high-affinity antibodies (with binding constant up to 2*10^11 M^-1 against the RBD) at concentrations down to 0.1 pM. Thus, our developed electrical Gr-FET immunosensors provide an appealing alternative to address the early screening/diagnosis as well as the analysis and rational design of neutralizing-antibody locking methods of this ongoing public health crisis.

    In silico elucidation revealed SARS CoV and MERS CoV Drug Compounds could be Potential Therapeutic Candidates against Post Fusion Core (S2) Protein of Novel Coronavirus (2019-nCov)

    Authors: Zainab Ayaz; Bibi Zainab; Arshad Mehmood Abbasi

    doi:10.21203/rs.3.rs-19589/v1 Date: 2020-03-26 Source: ResearchSquare

    Novel coronavirus (2019-nCoV), since its emergence from Wuhan China in December 31, 2019 is still uncontrolled and has raised attention around the globe. According to World health organization, up to March 20, 2020, globally 209,839 confirmed cases of COVID-19 MESHD have been reported along with 8778 deaths. 2019-nCoV is likely to be a recombinant of different coronaviruses such as SARS CoV MESHD and MERS CoV. Recent developments revealed that glycosylated spike (S) protein PROTEIN of 2019-nCov is contributing significantly in facilitating 2019- nCov infection in human body. The subunit (S1) of spike PROTEIN protein facilitates 2019-nCov binding with host cells’ receptors, while S2 subunit (post fusion core of 2019-nCov) is a key factor in fusion of 2019-nCov with host cell membrane and subsequent inoculation of its DNA in to the host cell. Therefore, in coronavirus infection MESHD, membrane fusion and receptor binding are critical. And if active sites of 2019-nCov spike protein PROTEIN S2 (post fusion core of 2019-nCov) are blocked, this may reduce COVID-19 MESHD infections in human. We use clustering based drug-drug interaction (DDI) networks and drug repositioning approach based on modularity to inhibit the membrane fusion and receptor binding capacity of 2019-nCov. About 150 drug compounds effective against SARS-CoV MESHD and MERS-CoV were retrieved, and screened on the basis of Lipinski rule of five. Clusters and strongly interacted DDI networks were generated in accordance to their modularity class, average path length and density. Promising drug candidates were then filtered by toxicity MESHD indicator and molecular docking. Our finding reveals that ZINC000029038525 and ZINC000029129064 drug compounds have significant binding potential with active sites of post fusion core of 2019-nCov ‘S2’ subunit and may inhibit membrane fusion and receptor binding capacity of 2019-nCov. Therefore, these drug compounds alone or in amalgamation could be strong and more effective therapeutic candidates against 2019-nCov infection MESHDs.

    Genotyping coronavirus SARS-CoV-2: methods and implications

    Authors: Changchuan Yin

    id:2003.10965v1 Date: 2020-03-24 Source: arXiv

    The emerging global infectious COVID-19 MESHD coronavirus disease MESHD by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. For understanding the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. We present an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The SNP genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. Our method serves a promising tool for monitoring and tracking the epidemic of pathogenic viruses in their gradual and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins PROTEIN and RNA polymerase, RNA primase, and nucleoprotein PROTEIN, undergo frequent mutations. These mutations are critical for vaccine development in disease control.

    Meplazumab treats COVID-19 MESHD pneumonia: an open-labelled, concurrent controlled add-on clinical trial

    Authors: Huijie Bian; Zhao-Hui Zheng; Ding Wei; Zheng Zhang; Wen-Zhen Kang; Chun-Qiu Hao; Ke Dong; Wen Kang; Jie-Lai Xia; Jin-Lin Miao; Rong-Hua Xie; Bin Wang; Xiu-Xuan Sun; Xiang-Min Yang; Peng Lin; Jie-Jie Geng; Ke Wang; Hong-Yong Cui; Kui Zhang; Xiao-Chun Chen; Hao Tang; Hong Du; Na Yao; Shuang-Shuang Liu; Lin-Na Liu; Zhe Zhang; Zhao-Wei Gao; Gang Nan; Qing-Yi Wang; Jian-Qi Lian; Zhi-Nan Chen; Ping Zhu

    doi:10.1101/2020.03.21.20040691 Date: 2020-03-24 Source: medRxiv

    Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 HGNC could bind spike protein PROTEIN of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 HGNC could block the infection of SARS-CoV-2 MESHD. We aimed to assess the efficacy and safety of meplazumab, a humanized anti- CD147 HGNC antibody, as add-on therapy in patients with COVID-19 MESHD pneumonia MESHD. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Disease MESHD Coronavirus Diseases MESHD released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia MESHD with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 MESHD pneumonia MESHD. Funding:National Science and Technology Major Project.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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