• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Optimizing peptide inhibitors of SARS-Cov-2 nsp10/nsp16 methyltransferase predicted through molecular simulation and machine learning.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Publisher version
    View Source
    Access full-text PDFOpen Access
    View Source
    Check access options
    Check access options
    Author
    Hamre, John R
    Jafri, M Saleet
    Date
    2022-02-28
    Journal
    Informatics in Medicine Unlocked
    Publisher
    Elsevier
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1016/j.imu.2022.100886
    Abstract
    Coronaviruses, including the recent pandemic strain SARS-Cov-2, use a multifunctional 2'-O-methyltransferase (2'-O-MTase) to restrict the host defense mechanism and to methylate RNA. The nonstructural protein 16 2'-O-MTase (nsp16) becomes active when nonstructural protein 10 (nsp10) and nsp16 interact. Novel peptide drugs have shown promise in the treatment of numerous diseases and new research has established that nsp10 derived peptides can disrupt viral methyltransferase activity via interaction of nsp16. This study had the goal of optimizing new analogous nsp10 peptides that have the ability to bind nsp16 with equal to or higher affinity than those naturally occurring. The following research demonstrates that in silico molecular simulations can shed light on peptide structures and predict the potential of new peptides to interrupt methyltransferase activity via the nsp10/nsp16 interface. The simulations suggest that misalignments at residues F68, H80, I81, D94, and Y96 or rotation at H80 abrogate MTase function. We develop a new set of peptides based on conserved regions of the nsp10 protein in the Coronaviridae species and test these to known MTase variant values. This results in the prediction that the H80R variant is a solid new candidate for potential new testing. We envision that this new lead is the beginning of a reputable foundation of a new computational method that combats coronaviruses and that is beneficial for new peptide drug development.
    Rights/Terms
    © 2022 The Authors.
    Keyword
    Anti-microbial peptide
    Antiviral peptide
    Covid-19
    Machine learning
    Molecular simulation
    Prediction
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/18183
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.imu.2022.100886
    Scopus Count
    Collections
    UMB Coronavirus Publications
    UMB Open Access Articles

    entitlement

    Related articles

    • Coronavirus nsp10/nsp16 Methyltransferase Can Be Targeted by nsp10-Derived Peptide In Vitro and In Vivo To Reduce Replication and Pathogenesis.
    • Authors: Wang Y, Sun Y, Wu A, Xu S, Pan R, Zeng C, Jin X, Ge X, Shi Z, Ahola T, Chen Y, Guo D
    • Issue date: 2015 Aug
    • Binding of the Methyl Donor <i>S</i>-Adenosyl-l-Methionine to Middle East Respiratory Syndrome Coronavirus 2'-<i>O</i>-Methyltransferase nsp16 Promotes Recruitment of the Allosteric Activator nsp10.
    • Authors: Aouadi W, Blanjoie A, Vasseur JJ, Debart F, Canard B, Decroly E
    • Issue date: 2017 Mar 1
    • Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex.
    • Authors: Chen Y, Su C, Ke M, Jin X, Xu L, Zhang Z, Wu A, Sun Y, Yang Z, Tien P, Ahola T, Liang Y, Liu X, Guo D
    • Issue date: 2011 Oct
    • Computational Investigation of Structural Dynamics of SARS-CoV-2 Methyltransferase-Stimulatory Factor Heterodimer nsp16/nsp10 Bound to the Cofactor SAM.
    • Authors: Sk MF, Jonniya NA, Roy R, Poddar S, Kar P
    • Issue date: 2020
    • Short peptides derived from the interaction domain of SARS coronavirus nonstructural protein nsp10 can suppress the 2'-O-methyltransferase activity of nsp10/nsp16 complex.
    • Authors: Ke M, Chen Y, Wu A, Sun Y, Su C, Wu H, Jin X, Tao J, Wang Y, Ma X, Pan JA, Guo D
    • Issue date: 2012 Aug
    DSpace software (copyright © 2002 - 2022)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.