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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (15)

ProteinN (1)

NSP5 (1)


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    A Super-Potent Tetramerized ACE2 HGNC Protein Displays Enhanced Neutralization of SARS-CoV-2 Virus Infection MESHD

    Authors: Ami Miller; Adam Leach; Jemima Thomas; Emma Bentley; Giada Mattiuzzo; Lijo John; Ali Mirazimi; Gemma Harris; Nadisha Nadisha Gamage; Stephen Carr; Hanif Ali; Rob Van Montfort; Terence Rabbitts; Craig McAndrew

    doi:10.21203/rs.3.rs-151560/v1 Date: 2021-01-20 Source: ResearchSquare

    Approaches are needed for therapy of the severe acute respiratory syndrome MESHD from SARS-CoV-2 coronavirus MESHD ( COVID-19 MESHD). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 HGNC (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2 HGNC, coupled to the human immunoglobulin g1 Fc region, using a self-assembling, tetramerization domain from p53 HGNC protein. This high molecular weight Quad protein ( ACE2 HGNC-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein PROTEIN and can form a complex with the spike protein PROTEIN plus anti-viral antibodies. The ACE2 HGNC-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 HGNC proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection MESHD with greatly enhanced efficacy. The ACE2 HGNC tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19 MESHD. In contrast to monoclonal antibodies, ACE2 HGNC decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 HGNC multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 HGNC receptor.

    Placental Pathology of the Third Trimester Pregnant Women from COVID-19 MESHD

    Authors: Likun Gao; Jiacai Ren; Li Xu; Xiaokang Ke; Lin Xiong; Xiaoli Tian; Cuifang Fan; Honglin Yan; Jingping Yuan

    doi:10.21203/rs.3.rs-104837/v1 Date: 2020-11-08 Source: ResearchSquare

    Aims: To explore the clinical characteristics and placental pathological changes of pregnant women with 2019 novel coronavirus (CoV) disease MESHD ( COVID-19 MESHD) in the third trimester, and to assess the possibility of vertical transmission.Methods and results: The placenta tissues were evaluated by using immunohistochemistry for inflammatory cells and Hofbauer cells, and using severe acute respiratory syndrome MESHD (SARS) CoV-2 RNA Fluorescence In-Situ Hybridization (FISH) and SARS-CoV-2 spike PROTEIN protein immunofluorescence (IF) double staining. All Eight placentas from the third trimester pregnancy women were studied. all patients were cured, no clinical or serological evidence pointed to vertical transmission of SARS-CoV-2. Features of maternal vascular malperfusion (MVM) such as increased syncytial knots were present in all 8 cases (8/8), and increased focal perivillous fibrin depositions were presented in 7 cases (7/8). No significate inflammatory cell reaction was noted in the placenta. The number of macrophages and inflammatory cells such as T cells, B cells and plasma cells in the placental villous was not significantly increased in all cases. Moreover, all of eight cases demonstrated negative results by FISH using a SARS-CoV-2 virus RNA probe and by IF using a monoclonal antibody against SARS-CoV-2 spike PROTEIN protein. Conclusions: We found no evidence of vertical transmission and adverse maternal-fetal outcomes in the placentas of third trimester COVID-19 MESHD pregnancy women, which provided further information for the clinical management of those women in the third trimester. However, further studies are still needed for patients with infections in different stage of gestation, especially in first and second trimester.

    Virtual Screening of Phytochemical Compounds as Potential Inhibitors against SARS-CoV-2 Infection MESHD

    Authors: Ram Kothandan; Cashlin Anna Suveetha Gnana Rajan; Janamitra Arjun; Rejoe Raymond Michael Raj; Sowfia Syed

    doi:10.21203/rs.3.rs-77456/v1 Date: 2020-09-14 Source: ResearchSquare

    Background: The present pandemic situation due to coronavirus has led to the search for newer prevention, diagnostic and treatment methods. The onset of the corona infection in a human results in acute respiratory illness MESHD followed by death if not diagnosed and treated with suitable anti-retroviral drugs. With the unavailability of the targeted drug treatment, several repurposed drugs are being used for treatment, However, the side-effects of the drugs urges us to move to a search for newer synthetic or phytochemical based drugs. The present study investigates the use of various phytochemicals virtually screened from various plant sources in Western Ghats, India and subsequently molecular docking studies were performed to identify the efficacy of the drug in retroviral infection particularly coronavirus infection MESHD.Results: Out of 57 phytochemical screened initially based on the structural and physicochemical properties, 39 were effectively used for the docking analysis. Finally 5 lead compound with highest hydrophobic interaction and number of H-bonds were screened. Results from the interaction analysis suggests, Piperolactam A to be pocketed well with good hydrophobic interaction with the residues in the binding region R1. ADME and toxicity MESHD profiling also reveals Piperolactam A with higher LogS vlaues indicating higher permeation and hydrophilicity. Toxicity MESHD profiling suggests that the 5 screened compounds to be relatively safe.Conclusion: The insilico methods used in this study suggests that the compound Piperolactum A to be the most effective inhibitor of S-protein PROTEIN from binding to the GRP78 receptor. By blocking the binding of the S-protein PROTEIN to the CS-GRP78 cell surface receptor, they can inhibit the binding of the virus to the host.

    Evidence of SARS-CoV-2 transcriptional activity in cardiomyocytes of COVID-19 MESHD patients without clinical signs of cardiac involvement

    Authors: Gaetano Pietro Bulfamante; Gianluca Lorenzo Perrucci; Monica Falleni; Elena Sommariva; Delfina Tosi; Carla Martinelli; Paola Songia; Paolo Poggio; Stefano Carugo; Giulio Pompilio

    doi:10.1101/2020.08.24.20170175 Date: 2020-08-26 Source: medRxiv

    Background - Cardiovascular complication in patients affected by novel Coronavirus respiratory disease MESHD ( COVID-19 MESHD) are increasingly recognized. However, although a cardiac tropism of SARS-CoV-2 MESHD for inflammatory cells in autopsy heart samples of COVID-19 MESHD patients has been reported, the presence of the virus in cardiomyocytes has not been documented yet. Methods - We investigated for SARS-CoV-2 presence in heart tissue autopsies of 6 consecutive COVID-19 MESHD patients deceased for respiratory failure MESHD showing no signs of cardiac involvement MESHD and with no history of heart disease MESHD. Cardiac autopsy samples were analysed by digital PCR, Western blot, immunohistochemistry, immunofluorescence, RNAScope, and transmission electron microscopy assays. Results - The presence of SARS-CoV-2 into cardiomyocytes was invariably detected. A variable pattern of cardiomyocytes injury MESHD was observed, spanning from the absence of cell death and subcellular alterations hallmarks to the intracellular oedema MESHD and sarcomere ruptures MESHD. In addition, we found active viral transcription in cardiomyocytes, by detecting both sense and antisense SARS-CoV-2 spike PROTEIN RNA. Conclusions - In this analysis of autopsy cases, the presence of SARS-CoV-2 into cardiomyocytes, determining variable patterns of intracellular involvement, has been documented. All these findings suggest the need of a cardiologic surveillance even in survived COVID-19 MESHD patients not displaying a cardiac phenotype, in order to monitor potential long-term cardiac sequelae.

    Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike PROTEIN protein

    Authors: Giuseppe Deganutti; Filippo Prischi; Christopher A. Reynolds

    doi:10.21203/rs.3.rs-64722/v1 Date: 2020-08-24 Source: ResearchSquare

    The recent outbreak of the respiratory syndrome MESHD-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease MESHD ( COVID-19 MESHD). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs approved for other diseases. The first interaction between the virus and the host cell is mediated by the spike protein PROTEIN on the virus surface and the human angiotensin-converting enzyme HGNC ( ACE2 HGNC). Small molecules able to bind the receptor-binding domain (RBD) of the spike protein PROTEIN and disrupt the binding to ACE2 HGNC would offer an important tool for slowing, or even preventing, the infection. Here, we screened 2421 approved small molecules in silico and validated the docking outcomes through extensive molecular dynamics simulations. Out of six drugs characterized as putative RBD binders, the cephalosporin antibiotic cefsulodin was further assessed for its effect on the binding between the RBD and ACE2 HGNC, suggesting the importance of considering the dynamic formation of the heterodimer when judging any potential candidate.

    Development of antibodies to pan-coronavirus spike peptides in convalescent COVID-19 MESHD patients

    Authors: Andrii Rabets; Galyna Bila; Roman Grytsko; Markian Samborsky; Yuriy Rebets; Sandor Vari; Quentin Pagneux; Alexandre Barras; Rabah Boukherroub; Sabine Szunerits; Rostyslav Bilyy

    doi:10.1101/2020.08.20.20178566 Date: 2020-08-22 Source: medRxiv

    Coronaviruses are sharing several protein regions notable the spike protein (S PROTEIN) on their enveloped membrane surface, with the S1 subunit recognizing and binding to the cellular receptor, while the S2 subunit mediates viral and cellular membrane fusion. This similarity opens the question whether infection with one coronavirus will confer resistance to other coronaviruses? Investigating patient serum samples after SARS-CoV-2 infection MESHD in cross-reactivity studies of immunogenic peptides from Middle East respiratory syndrome MESHD coronavirus (MERS-CoV), we were able to detect the production of antibodies also recognizing MERS virus antigens. The cross-reactive peptide comes from the heptad repeat 2 (HR2) domain of the MERS virus spike protein PROTEIN. Indeed, the peptide of the HR2 domain of the MERS spike protein PROTEIN, previously proven to induce antibodies against MERS-CoV is sharing 74% homology with the corresponding sequence of SARS-CoV-19 virus. Sera samples of 47 convalescent SARS-CoV-2 patients, validated by RT-PCR-negative testes 30 days post-infection, and samples of 40 sera of control patients (not infected with SARS-CoV-2 previously) were used to establish eventual cross-bind reactivity with the MERS peptide antigen. Significantly stronger binding (p<0.0001) was observed for IgG antibodies in convalescent SARS-CoV-2 patients compared to the control group. If used as an antigen, the peptide of the HR2 domain of the MERS spike protein PROTEIN allows discrimination between post-Covid populations from non-infected ones by the presence of antibodies in blood samples. This suggests that polyclonal antibodies established during SARS-CoV-2 infection MESHD has the ability to recognize and probably decrease infectiveness of MERS-CoV infections MESHD as well as other coronaviruses. The high homology of the spike protein PROTEIN domain suggests in addition that the opposite effect can also be true: coronaviral infections producing cross-reactive antibodies affective against SARS-CoV-19. The collected data prove in addition that despite the core HR2 region being hidden in the native viral conformation, its exposure during cell entry makes it highly immunogenic. Since inhibitory peptides to this region were previously described, this opens new possibilities in fighting coronaviral infections MESHD.

    N-terminal domain (NTD) of SARS-CoV-2 spike PROTEIN-protein structurally resembles MERS-CoV NTD sialoside-binding pocket

    Authors: Mayanka Awasthi; Sahil Gulati; Debi P. Sarkar; Swasti Tiwari; Suneel Kateriya; Peeyush Ranjan; Santosh Kumar Verma

    doi:10.21203/rs.3.rs-37300/v1 Date: 2020-06-22 Source: ResearchSquare

    COVID-19 MESHD novel coronavirus disease MESHD caused by SARS-CoV-2 causes severe lethal respiratory illness MESHD in humans and has recently developed into a worldwide pandemic. The lack of effective treatment strategy and vaccines against SARS-CoV-2 poses a threat to human health. Extremely high infection rate and multi-organ secondary infection within a short time period makes this virus more deadly and challenging for therapeutic interventions. Despite of high sequence similarity and utilization of common host-cell receptor, human angiotensin-converting enzyme-2 HGNC ( ACE2 HGNC) for virus entry, SARS-CoV-2 is much infectious than SARS-CoV MESHD. Structure-based sequence comparison of the N-terminal domain (NTD) of spike protein PROTEIN of MERS-CoV, SARS-CoV and SARS-CoV-2 MESHD illustrate three short stretches of amino acid motifs in SARS-CoV-2 , which appears to be the reminiscent of MERS-CoV sialoside binding pockets. These key differences with SARS-CoV MESHD and similarity with MERS-CoV MESHD, suggest an evolutionary adaptation of SARS-CoV-2 spike PROTEIN protein reciprocal interaction with host surface sialosides. 

    Evaluation of Neutralizing Antibodies against Highly Pathogenic Coronaviruses: A Detailed Protocol for a Rapid Evaluation of Neutralizing Antibodies Using Vesicular Stomatitis Virus (Vsv) Pseudovirus-Based Assay

    Authors: Sarah A. Almahboub; Abdullah Algaissi; Mohamed A. Alfaleh; M-Zaki ElAssouli; Anwar M. Hashem

    id:10.20944/preprints202005.0379.v1 Date: 2020-05-23 Source: Preprints.org

    Emerging highly pathogenic human coronaviruses (CoVs) represent a serious ongoing threat to the public health worldwide. The spike (S) proteins PROTEIN of CoVs are surface glycoproteins that facilitate viral entry into host cells via attachment to their respective cellular receptors. The S protein PROTEIN is believed to be a major immunogenic component of CoVs and a target for neutralizing antibodies (nAbs) and most candidate vaccines. Development of a safe and convenient assay is thus urgently needed to determine the prevalence of CoVs nAbs in the population, to study immune response in infected individuals, and to aid in vaccines and viral entry inhibitors evaluation. While live virus-based neutralization assays are used as gold standard serological methods to detect and measure nAbs, handling of highly pathogenic live CoVs requires strict bio-containment conditions in biosafety level-3 laboratories. On the other hand, use of replication-incompetent pseudoviruses bearing CoVs S proteins PROTEIN could represent a safe and useful method to detect nAbs in serum samples under biosafety level-2 conditions. Here, we describe a detailed protocol of a safe and convenient assay to generate vesicular stomatitis virus MESHD ( VSV MESHD)-based pseudoviruses to evaluate and measure nAbs against highly pathogenic CoVs. The protocol covers methods to produce VSV MESHD pseudovirus bearing the S protein PROTEIN of the Middle East respiratory syndrome-CoV (MERS-CoV) MESHD and the severe acute respiratory syndrome-CoV-2 MESHD (SARS-CoV-2), pseudovirus titration, and pseudovirus neutralizing assay. Such assay could be adapted by different laboratories and researchers working on highly pathogenic CoVs without the need to handle live viruses in biosafety level-3 environment.

    Mapping the Immunodominance Landscape of SARS-CoV-2 Spike PROTEIN Protein for the Design of Vaccines against COVID-19 MESHD

    Authors: Bao-zhong Zhang; Ye-fan Hu; Lin-lei Chen; Yi-gang Tong; Jing-chu Hu; Jian-piao Cai; Kwok-Hung Chan; Ying Dou; Jian Deng; Hua-rui Gong; Chaiyaporn Kuwentrai; Wenjun Li; Xiao-lei Wang; Hin Chu; Can-hui Su; Ivan Fan-Ngai Hung; Thomas Chung Cheung Yau; Kelvin Kai-Wang To; Kwok Yung Yuen; Jian-Dong Huang

    doi:10.1101/2020.04.23.056853 Date: 2020-04-24 Source: bioRxiv

    The ongoing coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic is a serious threat to global public health, and imposes severe burdens on the entire human society. The severe acute respiratory syndrome MESHD (SARS) coronavirus-2 (SARS-CoV-2) can cause severe respiratory illness MESHD and death MESHD. Currently, there are no specific antiviral drugs that can treat COVID-19 MESHD. Several vaccines against SARS-CoV-2 are being actively developed by research groups around the world. The surface S (spike) protein PROTEIN and the highly expressed internal N (nucleocapsid) protein PROTEIN of SARS-CoV-2 are widely considered as promising candidates for vaccines. In order to guide the design of an effective vaccine, we need experimental data on these potential epitope candidates. In this study, we mapped the immunodominant (ID) sites of S protein PROTEIN using sera samples collected from recently discharged COVID-19 MESHD patients. The SARS-CoV-2 S protein PROTEIN-specific antibody levels in the sera of recovered COVID-19 MESHD patients were strongly correlated with the neutralising antibody titres. We used epitope mapping to determine the landscape of ID sites of S protein PROTEIN, which identified nine linearized B cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-CoV-2 antibody binding sites. Peptides containing two out of the nine sites were tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised mice. This study for the first time provides human serological data for the design of vaccines against COVID-19 MESHD.

    Elucidating the differences in the molecular mechanism of receptor binding between 2019-nCoV and the SARS-CoV viruses using computational tools

    Authors: Toan The Nguyen; Hien Thi Thu Lai; Ly Hai Nguyen; Duc Nguyen-Manh; Agata The Kranjc Pietrucci

    doi:10.1101/2020.04.21.053009 Date: 2020-04-21 Source: bioRxiv

    The outbreak of the 2019-nCoV coronavirus causing severe acute respiratory syndrome MESHD which can be fatal, especially in elderly population, has been declared a pandemic by the World Health Organization. Many biotechnology laboratories are rushing to develop therapeutic antibodies and antiviral drugs for treatment of this viral disease. The viral CoV spike ( S) glycoprotein PROTEIN is one of the main targets for pharmacological intervention. Its receptor-binding domain (RBD) interacts with the human ACE2 HGNC receptor ensuring the entry of the viral genomes into the host cell. In this work, we report on the differences in the binding of the RBD of the previous coronavirus SARS-CoV MESHD and of the newer 2019-nCoV coronavirus to the human ACE2 HGNC receptor using atomistic molecular dynamics techniques. Our results show major mutations in the 2019-nCoV RBD with respect to the SARS-CoV RBD MESHD occurring at the interface of RBD- ACE2 HGNC complex. These mutations make the 2019-nCoV RBD protein backbone much more flexible, hydrophobic interactions are reduced and additional polar/charged residues appear at the interface. We observe that higher flexibility of the 2019-nCoV RBD with respect to the SARS-CoV RBD MESHD leads to a bigger binding interface between the 2019-nCoV RBD and ACE2 HGNC and to about 20% more contacts between them in comparison with SARS-CoV MESHD. Taken together, the 2019-nCoV RBD shows more stable binding interface and higher binding affinity for the ACE2 HGNC receptor. The mutations not only stabilize the binding interface, they also lead to overall more stable 2019-nCoV RBD protein structure, even far from the binding interface. Our results on the molecular differences in the binding between the two viruses can provide important inputs for development of appropriate antiviral treatments of the new viruses, addressing the necessity of ongoing pandemics.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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