Corpus overview


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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (5)

ComplexRdRp (5)

NSP5 (3)

ProteinN (2)

NSP6 (1)


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SARS-CoV-2 Proteins
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    A recombinant fragment of Human surfactant protein D HGNC binds Spike protein PROTEIN and inhibits infectivity and replication of SARS-CoV-2 in clinical samples

    Authors: Taruna Madan; Barnali Biswas; Praveen Varghese; Rambhadur Subedi; Hrishikesh Pandit; Susan Idicula-Thomas; Indra Kundu; Sheetalnath Babasaheb Rooge; Reshu Aggarwal; Dinesh Tripathi; Savneet Kaur; Ekta Gupta; Sanjeev Gupta

    doi:10.1101/2020.12.18.423415 Date: 2020-12-18 Source: bioRxiv

    Rationale COVID-19 MESHD is an acute infectious disease MESHD caused by the Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2). Human surfactant protein D HGNC ( SP-D HGNC) is known to interact with spike protein PROTEIN of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. ObjectiveThis study aimed to examine the potential of a recombinant fragment of human SP-D HGNC (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2 MESHD. MethodsrfhSP-D interaction with spike protein PROTEIN of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein PROTEIN and ACE-2 HGNC by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp PROTEIN gene of the virus using qPCR. Measurements and Main ResultsIn-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 PROTEIN were commonly involved in interacting with rfhSP-D and ACE-2 HGNC. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5M rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 M). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5M rfhSP-D. ConclusionsThese results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike PROTEIN protein and human ACE-2 HGNC, its host cell receptor, and a significant reduction in SARS-CoV-2 infection MESHD and replication in-vitro.

    Consistent and High-Frequency Identification of an Intra-Sample Genetic Variant of SARS-CoV-2 with Elevated Fusogenic Properties

    Authors: Lynda Rocheleau; Geneviève Laroche; Kathy Fu; Marceline Côté; Patrick M Giguère; Marc-André Langlois; Martin Pelchat; Peter Mohr; Remo Gamboni; Thanos D. Halazonetis; Kai-Thomas Schneider; Kristian Daniel Ralph Roth; Philipp Kuhn; Peggy Riese; Dorina Schäckermann; Janin Korn; Allan Koch; Susanne Zock-Emmenthal; Marlies Becker; Margitta Scholz; Gustavo Marçal Schmidt Garcia Moreira; Esther Veronika Wenzel; Giulio Russo; Hendrikus S.P. Garritsen; Sebastian Casu; Andreas Gerstner; Günter Roth; Andreas Hermann; Thomas Schirrmann; Stefan Dübel; André Frenzel; Joop Van den Heuvel; Luka Cicin-Sain; Maren Schubert; Michael Hust

    doi:10.1101/2020.12.03.409714 Date: 2020-12-03 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has a genome comprised of a ~30K nucleotides non-segmented, positive single-stranded RNA. Although its RNA-dependent RNA polymerase PROTEIN exhibits exonuclease proofreading activity, viral sequence diversity can be induced by replication errors and host factors. These variations can be observed in the population of viral sequences isolated from infected host cells and are not necessarily reflected in the genome of transmitted founder viruses. We profiled intra-sample genetic diversity of SARS-CoV-2 variants using 15,289 high-throughput sequencing datasets from infected individuals and infected cell lines. Most of the genetic variations observed, including C->U and G->U, were consistent with errors due to heat-induced DNA damage during sample processing, and/or sequencing protocols. Despite high mutational background, we confidently identified intra-variable positions recurrent in the samples analyzed, including several positions at the end of the gene encoding the viral S protein PROTEIN. Notably, most of the samples possesses a C->A missense mutation resulting in the S protein PROTEIN lacking the last 20 amino acids (S{Delta}20). Here we demonstrate that S{Delta}20 exhibits increased cell-to-cell fusion and syncytia formations MESHD. Our findings are suggestive of the consistent emergence of high-frequency viral quasispecies that are not horizontally transmitted but involved in intra-host infection MESHD and spread. Author summaryThe severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) and its associated disease, COVID-19 MESHD, has caused significant worldwide mortality and unprecedented economic burden. Here we studied the intra-host genetic diversity of SARS-CoV-2 genomes and identified a high-frequency and recurrent non-sense mutation yielding a truncated form of the viral spike protein PROTEIN, in both human COVID-19 MESHD samples and in cell culture experiments. Through the use of a functional assay, we observed that this truncated spike protein PROTEIN displays an elevated fusogenic potential and forms syncytia. Given the high frequency at which this mutation independently arises across various samples, it can be hypothesized that this deletion mutation provides a selective advantage to viral replication and may also have a role in pathogenesis in humans.

    Discovery of Natural Phenol Catechin as a Multitargeted Agent Against SARS-CoV-2 For the Plausible Therapy of COVID-19 MESHD

    Authors: Chandra Bhushan Mishra; Preeti Pandey; Ravi Datta Sharma; Raj Kumar Mongre; Andrew M Lynn; Rajendra Prasad; Raok Jeon; Amresh Prakash

    doi:10.26434/chemrxiv.12752402.v1 Date: 2020-08-04 Source: ChemRxiv

    The global pandemic crisis, COVID-19 MESHD caused by severe acute respiratory syndrome coronavirus MESHD 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines, are not turned to be realistic in the timeframe needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing as a clinical treatment strategy to control COVID-19 MESHD. Here we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, which are crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 72 FDA approved potential antiviral drugs against the target proteins: Spike (S PROTEIN) glycoprotein, human angiotensin-converting enzyme 2 ( hACE2 HGNC), 3-chymotrypsin- like cysteine protease PROTEIN ( 3CLpro PROTEIN), Cathepsin L HGNC, Nucleocapsid protein PROTEIN, RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) and nonstructural protein 6 ( NSP6 PROTEIN) resulted in the selection of seven drugs which preferentially binds to the target proteins. Further, the molecular interactions determined by MD simulation, free energy landscape and the binding free energy estimation, using MM-PBSA revealed that among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro PROTEIN, Cathepsin L HGNC, RBD of S protein PROTEIN, NSP-6, and Nucleocapsid protein PROTEIN. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol ( Cathepsin L HGNC) to -26.09 kcal/mol ( NSP6 PROTEIN). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favourable molecular interaction of catechin towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19 MESHD.

    Temporal evolution and adaptation of SARS-COV 2 codon usage

    Authors: Maddalena Dilucca; Sergio Forcelloni; Andrea Giansanti; Alexandros Georgakilas; Athanasia Pavlopoulou

    doi:10.1101/2020.05.29.123976 Date: 2020-06-03 Source: bioRxiv

    The outbreak of severe acute respiratory syndrome-coronavirus-2 MESHD (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 15,259 SARS-CoV-2 genomes isolated from 60 countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M PROTEIN), envelope (E), spike surface glycoprotein (S PROTEIN), nucleoprotein (N PROTEIN), non-structural 3C-like proteinase ( 3CLpro PROTEIN), ssRNA-binding protein ( RBP HGNC), 2-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase HGNC, RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN), Nsp7, Nsp8, and exonuclease ExoN. As a general rule, we find that SARS-CoV-2 genome tends to diverge over time by accumulating mutations on its genome and, specifically, on the coding sequences for proteins N PROTEIN and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S, Nsp7, NSp8, tend to use a norrower set of synonymous codons that are better optimized to the human host. Conversely, genes E PROTEIN and M consistently use a broader set of synonymous codons, which does not vary with respect to the reference genome. We identified key SARS-CoV-2 genes (S, N, ExoN, RNase, RdRp PROTEIN, Nsp7 and Nsp8) suggested to be causally implicated in the virus adaptation to the human host.

    Ayurveda botanicals in COVID-19 MESHD management: An in silico- multitarget approach

    Authors: Swapnil Borse; Manali Joshi; Akash Saggam; Vedika Bhat; Safal Walia; Sneha Sagar; Preeti Chavan-Gautam; Girish Tillu

    doi:10.21203/rs.3.rs-30361/v1 Date: 2020-05-19 Source: ResearchSquare

    The Coronavirus disease MESHD ( COVID-19 MESHD) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagiousdisease. Presently, existing anti-virals and disease-modifying agents are being repurposed to manage COVID-19 MESHD. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific anti-viralsand immunomodulators.The objective of this study is to explore the immunomodulatory and anti-SARS-CoV-2 potential of key phytoconstituents from Ayurveda based Rasayana drugs, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) using in silico approaches like network pharmacology, and molecular docking. The SWISS-ADME tool was used to predict the pharmacokinetic and pharmacodynamic (PK-PD) interactions and drug likeliness potential. Using these approaches we propose a library of phytomolecules with potential to be developed as phytopharmaceuticals for COVID 19 management.The plant extracts were prepared as per Ayurvedic procedures and a total of 31 phytoconstituents were identified using HPLC and MS studies. The network pharmacology model shows that these phytoconstituents possess the potential to modulate several immune pathways. Amongst the three botanicalsWithania somnifera was found to be the most potent immunomodulator through its potential to modulate T cell differentiation, NK cell cytotoxicity MESHD as well as T cell, B cell and NOD-like receptor signalling pathways.Molecular docking studies showed thatseveral phytoconstituents possess good affinity for the Spike protein PROTEIN, Main Protease PROTEIN and RNA dependent RNA polymerase PROTEIN of SARS-CoV-2 suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would beneficial herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals in the management of COVID-19 MESHD following rigorous experimental validation.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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