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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP3 (7)

ProteinS (4)

ProteinN (4)

NSP5 (3)

ORF8 (2)


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SARS-CoV-2 Proteins
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    Comparative host interactomes of the SARS-CoV-2 nonstructural protein 3 and human coronavirus homologs

    Authors: Katherine M Almasy; Jonathan P Davies; Lars Plate

    doi:10.1101/2021.03.08.434440 Date: 2021-03-08 Source: bioRxiv

    Human coronaviruses have become an increasing threat to global health; three highly pathogenic strains have emerged since the early 2000s, including most recently SARS-CoV-2, the cause of COVID-19 MESHD. A better understanding of the molecular mechanisms of coronavirus pathogenesis is needed, including how these highly virulent strains differ from those that cause milder, common-cold like disease. While significant progress has been made in understanding how SARS-CoV-2 proteins interact with the host cell, non-structural protein 3 PROTEIN ( nsp3 HGNC) has largely been omitted from the analyses. Nsp3 HGNC is a viral protease with important roles in viral protein biogenesis, replication complex formation, and modulation of host ubiquitinylation and ISGylation. Herein, we use affinity purification-mass spectrometry to study the host-viral protein-protein interactome of nsp3 HGNC from five coronavirus strains: pathogenic strains SARS-CoV-2, SARS-CoV MESHD, and MERS-CoV; and endemic common-cold strains hCoV-229E and hCoV-OC43. We divide each nsp3 HGNC into three fragments and use tandem mass tag technology to directly compare the interactors across the five strains for each fragment. We find that few interactors are common across all variants for a particular fragment, but we identify shared patterns between select variants, such as ribosomal proteins enriched in the N-terminal fragment ( nsp3 HGNC.1) dataset for SARS-CoV-2 and SARS-CoV MESHD. We also identify unique biological processes enriched for individual homologs, for instance nuclear protein important for the middle fragment of hCoV-229E, as well as ribosome biogenesis of the MERS nsp3 HGNC.2 homolog. Lastly, we further investigate the interaction of the SARS-CoV-2 nsp3 HGNC N-terminal fragment with ATF6 HGNC, a regulator of the unfolded protein response. We show that SARS-CoV-2 nsp3 HGNC.1 directly binds to ATF6 HGNC and can suppress the ATF6 HGNC stress response. Characterizing the host interactions of nsp3 HGNC widens our understanding of how coronaviruses co-opt cellular pathways and presents new avenues for host-targeted antiviral therapeutics.

    Novel Mutations in NSP1 HGNC and PLPro of SARS-CoV-2 NIB-1 Genome Mount for Effective Therapeutics

    Authors: Mohammad Uzzal Hossain; Arittra Bhattacharjee; Md. Tabassum Hossain Emon; Zeshan Mahmud Chowdhury; Md. Golam Mosaib; Md. Moniruzzaman; Md. Hadisur Rahman; Md. Nazrul Islam; Irfan Ahmed; Md. Ruhul Amin; Asif Rashed; Keshob Chandra Das; Chaman Ara Keya; Md. Salimullah; Maria Elvira Balcells; Luis Rojas; Bruno Nervi; Jyh Kae Nien; Javier Garate; Carolina Prieto; Sofia Palma; Carolina Escobar; Josefina bascunan; Rodrigo Munoz; Monica Pinto; Daniela Cardemil; Marcelo Navarrete; Soledad Reyes; Victoria Espinoza; Nicolas Yanez; Christian Caglevic

    doi:10.1101/2020.12.02.408229 Date: 2020-12-02 Source: bioRxiv

    Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2), the etiologic agent of Coronavirus Disease MESHD- 2019 ( COVID-19 MESHD), is rapidly accumulating new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Recently, we have reported a Sanger method based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel mutations in V121D, V843F, A889V and G1691C positions. V121D substitution has the potential to destabilize the Non-Structural Protein ( NSP-1 HGNC) which inactivates the type-1 Interferon-induced antiviral system hence this mutant could be the basis of attenuated vaccines against SARS-CoV-2. V843F, A889V and G1691C are all located in NSP3 PROTEIN NSP3 HGNC. G1691C can decrease the flexibility of the protein while V843F and A889V changed the binding pattern of SARS-CoV-2 Papain MESHD Papain-Like protease PROTEIN (PLPro) inhibitor GRL0617. V843F PLPro showed reduced affinity for Interferon Stimulating Gene-15 ( ISG-15 HGNC) protein whereas V843F+A889V double mutants exhibited the same binding affinity as wild type PLPro. Here, V843F is a conserved position of PLPro that damaged the structure but A889V, a less conserved residue, most probably neutralized that damage. Mutants of NSP1 HGNC could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro could be targeted to develop anti-SARS therapeutics.

    BCG vaccine derived peptides induce SARS-CoV-2 T cell cross-reactivity

    Authors: Peter J Eggenhuizen; Boaz H Ng; Janet Chang; Ashleigh L Fell; Wey Y Wong; Poh-yi Gan; Stephen R Holdsworth; Joshua D Ooi

    doi:10.1101/2020.11.21.20236018 Date: 2020-11-23 Source: medRxiv

    Epidemiological studies suggest that the Bacillus Calmette-Guerin (BCG) vaccine may have protective effects against coronavirus disease 2019 MESHD ( COVID-19 MESHD); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 MESHD (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) specific T cell response is unknown. Here, in silico, we identify 8 BCG derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 MESHD NSP3 PROTEIN NSP3 HGNC or NSP13 PROTEIN derived peptides. Using an in vitro co-culture system, we show that human CD4 HGNC+ and CD8 HGNC+ T cells primed with a BCG derived peptide developed enhanced reactivity to its corresponding SARS-CoV-2 derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 derived peptides. These findings provide a mechanistic basis for the epidemiologic observation that BCG vaccination confers protection from COVID-19 MESHD; and supports the use of BCG vaccination to induce cross-reactive SARS-CoV-2 specific T cell responses.

    In Silico studies of Natural compounds that inhibit SARS-CoV-2 Nucleocapsid Nsp1 HGNC/ Nsp3 HGNC proteins mediated Viral Replication and Pathogenesis

    Authors: Hemanth Kumar Manikyam

    doi:10.21203/rs.3.rs-103400/v1 Date: 2020-11-05 Source: ResearchSquare

    Highly Transmissible and pathogenic coronavirus that emerged in late December of 2019 caused Severe acute respiratory syndrome MESHD (SARS-CoV-2), which challenged human health and public safety. Severity of the disease depends on the viral load and the type of mutation that occurred in the coronavirus. Nonstructural proteins like, Nsp1 HGNC, Nsp3 HGNC, Nsp12 and Nsp13 including other viral proteins plays important role during viral replication life cycle. Viral Replication initiated by hacking the host cellular mechanism either by synergy or by suppression using nucleocapsid proteins PROTEIN of the virus. Spike (S) protein PROTEIN of the SARS-CoV-2 uses angiotensin-converting enzyme II ( ACE2 HGNC) and TRMPSS as a cell entry. Once virus enters host cell, nucleocapsid proteins PROTEIN along with its genome is releases from endosomes into cytosol of the host cell. Ca2+/ CaM HGNC ( Calmodulin HGNC)/Calcineurin complex of the host cell plays important role during viral replication which is mediated by nucleocapsid proteins PROTEIN of the virus. Nsp1 HGNC/ Nsp3 HGNC nonstructural proteins triggers synergetic activity with CD147 HGNC/ CyPA HGNC/ HSPG HGNC pathway and TRMP2/ADPr/Ca+2 mediated Ca2+/CaM ( Calmodulin HGNC)/Calcineurin synthesis and free radicle generation in mitochondria leading to viral replication and severe chemokine activation pathways. Docking studies were carried out to inhibit Cyclophilin A and TRMP2 proteins as drug targets. Natural compounds like Withanolide A, Columbin, Cucurbitacin E, Boswellic acid along with Cyclosporines, Vitamin E and N-Acetyl cysteine ( NAC HGNC) were selected as ligands to study docking studies. Withanolide A and Cyclosporines had shown good inhibition activity against Cyclophilin A, whereas Columbin, Boswellic acid, Cucurbitacin E, Vitamin E and N-Acetyl cysteine ( NAC HGNC) had shown inhibitory activity against TRMP2. Thus, we suggest conducting further studies to conclude above pathways mechanism and inhibitory effect of natural compounds against the Nsp1 HGNC/ Nsp3 HGNC mediated pathways Invitro and In vivo.

    Drug Design and Repurposing with DockThor-VS Web Server: Virtual Screening focusing on SARS-CoV-2 Therapeutic Targets and their Non-Synonym Variants

    Authors: Isabella A. Guedes; Leon S. C. Costa; Karina B. dos Santos; Ana L. M. Karl; Gregório K. Rocha; Iury M. Teixeira; Marcelo M. Galheigo; Vivian Medeiros; Eduardo Krempser; Fábio L. Custódio; Helio J. C. Barbosa; Marisa F. Nicolás; Laurent E. Dardenne

    doi:10.21203/rs.3.rs-96789/v1 Date: 2020-10-22 Source: ResearchSquare

    The COVID-19 MESHD caused by the SARS-CoV-2 virus was declared as a pandemic disease in March 2020 by the World Health Organization (WHO). Structure-Based Drug Design strategies based on docking methodologies have been widely used for both new drug development and drug repurposing to find effective treatments against this disease. In this work, we present the developments implemented in the DockThor-VS web server to provide a virtual screening (VS) platform with curated structures of potential therapeutic targets from SARS-CoV-2 incorporating genetic information regarding relevant non-synonymous variations. The web server facilitates repurposing VS experiments providing curated libraries of currently available drugs on the market. Currently, DockThor-VS provides ready-for-docking 3D structures for wild type and selected mutations for Nsp3 HGNC (papain-like, PLpro PROTEIN domain), Nsp5 HGNC ( Mpro PROTEIN, 3CLpro PROTEIN), Nsp12 ( RdRp PROTEIN), Nsp15 (NendoU), N protein PROTEIN and Spike. We performed VS experiments of FDA-approved drugs considering the therapeutic targets available at the web server to assess the impact of considering different structures and mutations in the identification of possible new treatments of SARS-CoV-2 infections MESHD. The DockThor-VS is freely available at www.dockthor.lncc.br.

    Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2

    Authors: Vipin Gupta; Shazia Haider; Mansi Verma; Kalaiarasan Ponnusamy; Md. Zubbair Malik; Nirjara Singhvi; Helianthous Verma; Roshan Kumar; Utkarsh Sood; Princy Hira; Shiva Satija; Rup Lal

    doi:10.1101/2020.06.20.162560 Date: 2020-06-20 Source: bioRxiv

    SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome MESHD resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 MESHD COVID-19 MESHD pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3 HGNC, ORF8 PROTEIN, Nsp13, S, Nsp12, Nsp2 HGNC and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 HGNC was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins PROTEIN with ACE2 HGNC, but it also showed better interaction with TMPRSS2 HGNC receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A HGNC, MYO5B HGNC & MYO5C HGNC had maximum interaction with viral hub proteins (Nucleocapsid PROTEIN, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 HGNC proteins which could be an effective target for COVID-19 MESHD treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia MESHD and thrombotic MESHD conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 HGNC and N proteins PROTEIN which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.

    SARS-CoV-2 proteases cleave IRF3 HGNC and critical modulators of inflammatory pathways ( NLRP12 HGNC and TAB1): implications for disease presentation across species and the search for reservoir hosts.

    Authors: Mehdi Moustaqil; Emma Ollivier; Hsin-Ping Chiu; Paulina Rudolffi-Soto; Sarah Van Tol; Christian Stevens; Akshay Bhumkar; Dominic J.B. Hunter; Alexander N. Freiberg; David Jacques; Benhur Lee; Emma Sierecki; Yann Gambin

    doi:10.1101/2020.06.05.135699 Date: 2020-06-05 Source: bioRxiv

    The genome of SARS-CoV-2 ( SARS2 MESHD) encodes for two viral proteases ( NSP3 PROTEIN NSP3 HGNC/ papain-like protease PROTEIN and NSP5 HGNC NSP5 PROTEIN/ 3C-like protease or major protease) that are responsible for cleaving viral polyproteins for successful replication. NSP3 PROTEIN NSP3 HGNC and NSP5 HGNC NSP5 PROTEIN of SARS-CoV (SARS1) are known interferon antagonists. Here, we examined whether the protease function of SARS2 MESHD NSP3 HGNC NSP3 PROTEIN and NSP5 PROTEIN NSP5 HGNC target proteins involved in the host innate immune response. We designed a fluorescent based cleavage assay to rapidly screen the protease activity of NSP3 PROTEIN NSP3 HGNC and NSP5 PROTEIN NSP5 HGNC on a library of 71 human innate immune proteins (HIIPs), covering most pathways involved in human innate immunity. By expressing each of these HIIPs with a genetically encoded fluorophore in a cell-free system and titrating in the recombinant protease domain of NSP3 HGNC NSP3 PROTEIN or NSP5 PROTEIN NSP5 HGNC, we could readily detect cleavage of cognate HIIPs on SDS-page gels. We identified 3 proteins that were specifically and selectively cleaved by NSP3 PROTEIN NSP3 HGNC or NSP5 HGNC NSP5 PROTEIN: IRF-3 HGNC, and NLRP12 HGNC and TAB1, respectively. Direct cleavage of IRF3 HGNC by NSP3 HGNC NSP3 PROTEIN could explain the blunted Type- I IFN response seen during SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs while NSP5 PROTEIN NSP5 HGNC mediated cleavage of NLRP12 HGNC and TAB1 point to a molecular mechanism for enhanced production of IL-6 HGNC and inflammatory response observed in COVID-19 MESHD patients. Surprisingly, both NLRP12 HGNC and TAB1 have each two distinct cleavage sites. We demonstrate that in mice, the second cleavage site of NLRP12 is absent. We pushed this comparative alignment of IRF-3 and NLRP12 homologs and show that the lack or presence of cognate cleavage motifs in IRF-3 and NLRP12 could contribute to the presentation of disease in cats and tigers, for example. Our findings provide an explanatory framework for in-depth studies into the pathophysiology of COVID-19 MESHD and should facilitate the search or development of more effective animal models for severe COVID-19 MESHD. Finally, we discovered that one particular species of bats, Davids Myotis, possesses the five cleavage sites found in humans for NLRP12 HGNC, TAB1 and IRF3 HGNC. These bats are endemic from the Hubei province in China and we discuss its potential role as reservoir for the evolution of SARS1 and SASR2.

    Shortlisting Phytochemicals Exhibiting Inhibitory Activity against Major Proteins of SARS-CoV-2 through Virtual Screening

    Authors: Saranya Nallusamy; Jayakanthan Mannu; Caroline Ravikumar; Kandavelmani Angamuthu; Bharathi Nathan; Kumaravadivel Nachimuthu; Gnanam Ramasamy; Raveendran Muthurajan; Mohankumar Subbarayalu; Kumar Neelakandan

    doi:10.21203/rs.3.rs-31834/v1 Date: 2020-05-27 Source: ResearchSquare

    Severe Acute Respiratory Syndrome Corona Virus 2 MESHD (SARS-CoV-2) declared as a pandemic by WHO that has affected more than 40 lakh peoples and caused death MESHD of more than 2 lakh individuals across the globe. Limited availability of genomic information of SARS-CoV-2 and non-availability of vaccines and effective drugs are major problems responsible for the ineffective control and management of this pandemic. Several attempts have been made to explore repurposing existing drugs known for their anti-viral activities, and test the traditional herbal medicines known for their health benefiting and immune boosting activity against SARS-CoV-2.In this study, efforts were made to examine the potential of 721 phytochemicals of 37 plant species in inhibiting major protein targets namely, spike glycoprotein PROTEIN, main protease PROTEIN (MPro), NSP3 HGNC NSP3 PROTEIN, NSP9 PROTEIN, NSP15 PROTEIN, NSP10 PROTEIN- NSP16 PROTEIN and RNA dependent RNA polymerase PROTEIN of SARS-CoV-2 through virtual screening approach. Results of our experiments revealed that SARS-CoV-2 MPro shared significant dissimilarities against SARS-CoVMPro and MERS-CoVMPro indicating the need for discovering novel drugs. This study has identified the phytochemical cyanin (Zingiber officinale) exhibiting broad spectrum inhibitory activity against main proteases PROTEIN of all the three Coronaviruses. Amentoflavone, agathisflavone, catechin-7-o-gallate and chlorogeninwere shown to exhibit multi target inhibitory activity. This study has identified Mangifera indica, Anacardium occidentale, Vitex negundo, Solanum nigrum, Pedalium murex, Terminalia chebula, Azadirachta indica, Cissus quadrangularis, Clerodendrum serratum and Ocimum basilicum as potential sources of phytochemicals combating n COVID-19 MESHD. More interestingly, this study has generated evidences for the anti-viral properties of the traditional herbal formulation “Kabasura kudineer” recommended by AYUSH, a unit of Government of India. Testing of short listed phytochemicals through clinical trials will help in developing effective formulation for management of this pandemic disease. Genomic analysis of identified herbal plants will help in unravelling molecular complexity of therapeutic and anti-viral properties and will pave way for designing synthetic drugs. 

    Molecular Docking, ADME Analysis, and Estimation of MM/GBSA Binding-Free Energies of Coumarin Derivatives as Potential Inhibitors of SARS CoV-2 Receptors

    Authors: Akhilesh Kumar Maurya; Nidhi Mishra

    doi:10.21203/rs.3.rs-25847/v1 Date: 2020-04-28 Source: ResearchSquare

    Coronavirus Disease ( COVID-19 MESHD) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2). Currently, there is no specific drug for the therapy of COVID-19 MESHD. In the present study, in silico study have been done to find out possible inhibitors of SARS CoV-2. Coumarin derivatives with 2755 compounds were virtually screen against methyltransferase-stimulatory factor complex of NSP16 PROTEIN and NSP10 PROTEIN, NSP15 PROTEIN Endoribonuclease, ADP ribose phosphatase ( ADRP HGNC)of NSP3 PROTEIN NSP3 HGNC and protease enzymes of SARS CoV-2. Docked top five compounds showed good docking scores and free energy of binding with the respective receptors. ADME/T analysis of docked compound shows the docked ligands are showing drug-likeness properties.

    The global population of SARS-CoV-2 is composed of six major subtypes

    Authors: Ivair Jose Morais Junior; Richard Costa Polveiro; Gabriel Medeiros Souza; Daniel Inserra Bortolin; Flavio Tetsuo Sassaki; Alison Talis Martins Lima

    doi:10.1101/2020.04.14.040782 Date: 2020-04-15 Source: bioRxiv

    The World Health Organization characterized the COVID-19 MESHD as a pandemic in March 2020, the second pandemic of the 21st century. Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is a positive-stranded RNA betacoronavirus of the family Coronaviridae. Expanding virus populations, as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for a robust clustering. Here, we proposed the subdivision of the global SARS-CoV-2 population into sixteen well-defined subtypes by focusing on the widely shared polymorphisms in nonstructural ( nsp3 HGNC, nsp4 HGNC, nsp6, nsp12, nsp13 and nsp14) cistrons, structural (spike and nucleocapsid) and accessory ( ORF8 PROTEIN) genes. Six virus subtypes were predominant in the population, but all sixteen showed amino acid replacements which might have phenotypic implications. We hypothesize that the virus subtypes detected in this study are records of the early stages of the SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world, a typical founder effect. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing the candidate vaccines or drugs.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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