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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (689)

NSP5 (33)

ProteinN (29)

ProteinS1 (26)

ComplexRdRp (23)


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SARS-CoV-2 Proteins
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    Age-dependent appearance of SARS-CoV-2 entry cells in mouse chemosensory systems reflects COVID-19 MESHD anosmia MESHD and ageusia symptoms MESHD.

    Authors: Julien Brechbuhl; Dean Wood; Sofiane Bouteiller; Ana Catarina Lopes; Chantal Verdumo; Marie-Christine Broillet

    doi:10.1101/2021.03.29.437530 Date: 2021-03-29 Source: bioRxiv

    COVID-19 pandemic MESHD has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia MESHD. Evidence for the presence of the cellular entry sites of the virus, the ACE2 HGNC and the TMPRSS2 HGNC proteins, has been reported in non-chemosensory cells in the nose and mouth of the rodents, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2 and TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identified the virus target cells to be of basal and sensory origin and we revealed their age-dependent appearance. Our results not only clarify human viral-induced sensory symptoms but also propose new investigative perspectives based on ACE2 HGNC-humanized mouse models.

    Preliminary report on SARS-CoV-2 Spike PROTEIN mutation T478K

    Authors: Simone Di Giacomo; Daniele Mercatelli; Amir Rakhimov; Federico M Giorgi

    doi:10.1101/2021.03.28.437369 Date: 2021-03-29 Source: bioRxiv

    Several SARS-CoV-2 variants have emerged, posing a renewed threat to COVID-19 MESHD containment and to vaccine and drug efficacy. In this study, we analyzed more than 820,000 SARS-CoV-2 genomic sequences deposited up to March 26, 2021 and identified a novel T478K mutation located on the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein. The mutation is structurally located in the region of interaction with human receptor ACE2 HGNC and was detected in 4,214 distinct cases. We show that T478K has appeared and risen in frequency since January 2021, predominantly in Mexico and North America, but we could also detect it in several European countries.

    Increased angiotensin-converting enzyme 2 HGNC, sRAGE and immune activation, but lowered calcium and magnesium in COVID-19 MESHD: association with chest CT abnormalities MESHD and lowered peripheral oxygen saturation.

    Authors: Hussein Al-Hakeim; Hawraa Al-Jassas; Gerwyn Morris; Michael Maes

    doi:10.1101/2021.03.26.21254383 Date: 2021-03-26 Source: medRxiv

    Background. The characterization of new biomarkers of COVID-19 MESHD is extremely important. Few studies measured the soluble receptor for advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), calcium and magnesium in COVID-19 MESHD. Aims: To measure sRAGE, ACE2 HGNC, interleukin (IL)-6 HGNC, IL-10 HGNC, CRP HGNC, calcium, magnesium, and albumin in COVID-19 MESHD patients in association with peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) including ground glass opacities. Methods. This study measured sRAGE, ACE2 HGNC, IL-6 HGNC, IL-10 HGNC, CRP HGNC using ELISA techniques, and calcium, magnesium, and albumin using a spectrophotometric method in 60 COVID-19 MESHD patients and 30 healthy controls. Results. COVID-19 MESHD is characterized by significantly increased IL-6 HGNC, CRP HGNC, IL-10 HGNC, sRAGE, ACE2 HGNC, and lowered levels of SpO2, albumin, magnesium and calcium. Neural networks showed that a combination of calcium, IL-6 HGNC, CRP HGNC, and sRAGE yielded an accuracy of 100% in detecting COVID-19 MESHD patients with calcium being the most important predictor followed by IL-6 HGNC, and CRP HGNC. COVID-19 MESHD patients with CCTAs showed lower SpO2 and albumin levels than those without CCTAs. SpO2 was significantly and inversely correlated with IL-6 HGNC, IL-10 HGNC, CRP HGNC, sRAGE, and ACE2 HGNC, and positively with albumin, magnesium and calcium. Patients with positive IgG results showed a significant elevation in the serum level of IL-6 HGNC, sRAGE, and ACE2 HGNC compared to the negatively IgG patient subgroup. Conclusion. The results show that immune-inflammatory and RAGE HGNC pathway biomarkers may be used as external validating criterion for the diagnosis COVID-19 MESHD. Those pathways coupled with lowered SpO2, calcium and magnesium are drug targets that may help to reduce the consequences of COVID-19 MESHD.

    Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 RBD variants with a novel competitive multiplex assay

    Authors: Ester Lopez; Ebene R Haycroft; Amy Adair; Francesca L Mordant; Matthew O'Neill; Phillip Pymm; Samuel Redmond; Nicholas A Gherardin; Adam K Whearley; Jennifer A Juno; Kevin J Selva; Samantha Davis; Leigh Harty; Damian F.J. Purcell; Kanta Subbarao; Dale I Godfrey; Stephen J Kent; Wai-Hong Tham; Amy W Chung

    doi:10.1101/2021.03.20.21254037 Date: 2021-03-26 Source: medRxiv

    The SARS-CoV-2 Receptor Binding Domain (RBD) is both the principal target of neutralizing antibodies, and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate that immune escape can occur through two mechanisms, antibodies that fail to recognize mutations, along with antibodies that have reduced inhibitory capacity due to enhanced variant RBD- ACE2 HGNC affinity. A competitive approach where antibodies simultaneously compete with ACE2 HGNC for binding to the RBD may therefore more accurately reflect the physiological dynamics of infection. We describe the enhanced affinity of RBD variants N439K, S477N, Q493L, S494P and N501Y to the ACE2 HGNC receptor, and demonstrate the ability of this assay to bridge a major gap for SARS-CoV-2 research; informing selection of complementary monoclonal antibody candidates and the rapid identification of immune escape to emerging RBD variants following vaccination or natural infection.

    Evolutionary differences in the ACE2 HGNC reveals the molecular origins of COVID-19 MESHD susceptibility

    Authors: Ryan R. Cheng; Esteban Dodero-Rojas; Michele Di Pierro; José Nelson Onuchic

    doi:10.1101/2021.03.25.437113 Date: 2021-03-26 Source: bioRxiv

    We explore the energetic frustration patterns associated with the binding between the SARS-CoV-2 spike PROTEIN protein and the ACE2 receptor protein in a broad selection of animals. Using energy landscape theory and the concept of energy frustration--theoretical tools originally developed to study protein folding--we are able to identify interactions among residues of the spike protein PROTEIN and ACE2 HGNC that result in COVID-19 MESHD resistance. This allows us to identify whether or not a particular animal is susceptible to COVID-19 MESHD from the protein sequence of ACE2 HGNC alone. Our analysis predicts a number of experimental observations regarding COVID-19 MESHD susceptibility, demonstrating that this feature can be explained, at least partially, on the basis of theoretical means.

    Toward Community Surveillance: Detecting Intact SARS-CoV-2 Using Exogeneous Oligonucleotide Labels

    Authors: Thomas R Carey; Molly Kozminsky; Jennifer Hall; Valerie Vargas-Zapata; Kristina Geiger; Laurent Coscoy; Lydia L Sohn

    doi:10.1101/2021.03.23.21254201 Date: 2021-03-26 Source: medRxiv

    The persistence of the COVID-19 pandemic MESHD demands a dramatic increase in testing efficiency. Testing pooled samples for SARS-CoV-2 could meet this need; however, the sensitivity of RT-qPCR, the gold standard, significantly decreases with an increasing number of samples pooled. Here, we introduce DIVER, a method that quantifies intact virus and is robust to sample dilution. DIVER first tags viral particles with exogeneous oligonucleotides, then captures the tagged particles on ACE2 HGNC-functionalized beads, and finally quantifies the oligonucleotide tags using qPCR. Using spike-presenting liposomes and Spike-pseudotyped lentivirus as SARS-CoV-2 models, we show that DIVER can detect 1x105 liposomes and 100 pfu lentivirus and can successfully identify positive samples in pooling experiments. Overall, DIVER is well-positioned for efficient sample pooling and expanded community surveillance.

    Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike PROTEIN protein and the human ACE2 HGNC receptor

    Authors: Chen Chen; Veda Sheeresh Boorla; Deepro Banerjee; Ratul Chowdhury; Victoria S Cavener; Ruth H Nissly; Abhinay Gontu; Nina R Boyle; Kurt Vandegrift; Meera Surendran Nair; Suresh V Kuchipudi; Costas D Maranas

    doi:10.1101/2021.03.24.436885 Date: 2021-03-25 Source: bioRxiv

    The association of the receptor binding domain (RBD) of SARS-CoV-2 viral spike with human angiotensin converting enzyme HGNC ( hACE2 HGNC) represents the first required step for viral entry. Amino acid changes in the RBD have been implicated with increased infectivity and potential for immune evasion. Reliably predicting the effect of amino acid changes in the ability of the RBD to interact more strongly with the hACE2 HGNC receptor can help assess the public health implications and the potential for spillover and adaptation into other animals. Here, we introduce a two-step framework that first relies on 48 independent 4-ns molecular dynamics ( MD MESHD) trajectories of RBD- hACE2 HGNC variants to collect binding energy terms decomposed into Coulombic, covalent, van der Waals, lipophilic, generalized Born electrostatic solvation, hydrogen-bonding, {pi}-{pi} packing and self-contact correction terms. The second step implements a neural network to classify and quantitatively predict binding affinity using the decomposed energy terms as descriptors. The computational base achieves an accuracy of 82.2% in terms of correctly classifying single amino-acid substitution variants of the RBD as worsening or improving binding affinity for hACE2 HGNC and a correlation coefficient r of 0.69 between predicted and experimentally calculated binding affinities. Both metrics are calculated using a 5-fold cross validation test. Our method thus sets up a framework for effectively screening binding affinity change with unknown single and multiple amino-acid changes. This can be a very valuable tool to predict host adaptation and zoonotic spillover of current and future SARS-CoV-2 variants.

    Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses MESHD

    Authors: Alvaro A Ordonez; Cynthia K Bullen; Andres F Villabona-Rueda; Elizabeth A Thompson; Mitchell L Turner; Stephanie L Davis; Oliver Komm; Jonathan D Powell; Robert H Yolken; Sanjay K Jain; Lorraine Jones-Brando

    doi:10.1101/2021.03.25.437060 Date: 2021-03-25 Source: bioRxiv

    Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 MESHD ( COVID-19 MESHD), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19 MESHD. We evaluated the antiviral activity of sulforaphane ( SFN HGNC), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous vegetables with limited side effects. SFN inhibited in vitro replication of four strains of SARS-CoV-2 as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection MESHD in vitro. Prophylactic administration of SFN to K18- hACE2 HGNC mice prior to intranasal SARS-CoV-2 infection MESHD significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury MESHD and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN is a promising treatment for prevention of coronavirus infection MESHD or treatment of early disease.

    The SARS-CoV-2 receptor angiotensin-converting enzyme 2 ( ACE2 HGNC) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome MESHD: analysis of high-throughput genetic, epigenetic, and gene expression studies

    Authors: João Malato; Franziska Sotzny; Sandra Bauer; Helma Freitag; André Fonseca; Anna D Grabowska; Luís Graça; Clara Cordeiro; Luís Nacul; Eliana M Lacerda; Jesus Castro Marrero; Carmen Scheibenbogen; Francisco Westermeier; Nuno Sepulveda

    doi:10.1101/2021.03.23.21254175 Date: 2021-03-24 Source: medRxiv

    Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome MESHD ( ME/CFS MESHD) show specific epigenetic and gene expression signatures of the disease. However, it is unknown whether these signatures in ME/CFS MESHD include abnormal levels of the human angiotensin-converting enzyme ACE HGNC and ACE2 HGNC, the latter being the main receptor described for host-cell invasion by SARS-CoV-2. To investigate that, we first reviewed published case-control genome-wide association studies based on single nucleotide polymorphism data, case-control epigenome-wide association studies based on DNA methylation data, and case-control gene expression studies based on microarray data. From these published studies, we did not find any evidence for a difference between patients with ME/CFS MESHD and healthy controls in terms of genetic variation, DNA methylation, and gene expression levels of ACE HGNC and ACE2 HGNC. In line with this evidence, the analysis of a new data set on the ACE HGNC/ ACE2 HGNC gene expression in peripheral blood mononuclear cells did not find any differences between a female cohort of 37 patients and 34 age-matched healthy controls. Future studies should be conducted to extend this investigation to other potential receptors used by SARS-CoV-2. These studies will help researchers and clinicians to better assess the health risk imposed by this virus when infecting patients with this debilitating disease.

    Computer-Aided Approaches to De Novo Design of drug candidates targeting the SARS-CoV-2 Spike PROTEIN protein bound to angiotensin converting enzyme 2 HGNC ( ACE2 HGNC)

    Authors: Konstantinos Kalamatianos

    doi:10.26434/chemrxiv.14242082.v1 Date: 2021-03-24 Source: ChemRxiv

    In this study a computer-aided approach to de novo design of chemical entities with drug-like properties against the SARS-CoV-2 Spike PROTEIN protein bound to ACE2 HGNC is presented. A structure-based de novo drug design tool LIGANN was used to produce complementary ligand shapes to the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein (6M0J). The obtained ligand structures - potential drug candidates – were optimized and virtually screened. Hit ligands were considered all that showed initial binding energy scores ≤ -9.0 kcal.mol-1 for the protein. These compounds were tested for drug-likeness (Lipinski’s rule and BOILED Permeation Predictive Model). All satisfying the criteria were re-optimized (geometry & frequencies) at the HF-3c33 level of theory and virtually screened against 6M0J. Molecular dynamics ( MD MESHD) simulations were used to assess the structural stability of selected 6M0J/novel compound complexes. Synthetic pathways for selected compounds from commercially available starting materials are proposed.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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