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  1. Article: Discovery of Drug-like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3

    Virdi, Rajdeep S. / Bavisotto, Robert V. / Hopper, Nicholas C. / Frick, David N.

    Abstract: The Mac1 domain of the multifunctional SARS-CoV-2 non-structural protein 3 (nsp3) is a potential COVID-19 drug target because it is suspected to enhance the ability of the virus to evade the human immune system The SARS-CoV-2 Mac1 domain binds ADP-ribose ...

    Abstract The Mac1 domain of the multifunctional SARS-CoV-2 non-structural protein 3 (nsp3) is a potential COVID-19 drug target because it is suspected to enhance the ability of the virus to evade the human immune system The SARS-CoV-2 Mac1 domain binds ADP-ribose and proteins harboring this important post-translational modification Small molecules that bind the Mac1 domain in place of ADP-ribose might therefore be useful as molecular probes or scaffolds for antiviral drug discovery Two high throughput screens were used here to identify such ligands in small libraries of drugs and drug-like compounds The first screen used differential scanning fluorimetry (DSF, aka the thermal shift or ThermoFluor assay) to examine the melting temperature of SARS-CoV-2 Mac1 domain in the presence of various compounds In the second screen, various high-resolution SARS-CoV-2 Mac1 structures were used with Autodock VINA to identify potential ligands Numerous hit compounds were either steroids (estradiol valerate & flunisolide), beta-lactams (cefaclor & cefatrizine), or benzimidazoles (telmisartan, rabeprazole, omeprazole, & esomeprazole) Isothermal titration calorimetry was used to confirm that rabeprazole, omeprazole, and compounds in other chemical classes, such as irinotecan, nifedipine, trifluoperazine, bind SARS-CoV-2 Mac1 with an affinity similar to ADP-ribose
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #665871
    Database COVID19

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  2. Article ; Online: Discovery of Drug-like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3

    Virdi, Rajdeep S / Bavisotto, Robert V / Hopper, Nicholas C / Frick, David

    bioRxiv

    Abstract: The Mac1 domain of the multifunctional SARS-CoV-2 non-structural protein 3 (nsp3) is a potential COVID-19 drug target because it is suspected to enhance the ability of the virus to evade the human immune system. The SARS-CoV-2 Mac1 domain binds ADP- ... ...

    Abstract The Mac1 domain of the multifunctional SARS-CoV-2 non-structural protein 3 (nsp3) is a potential COVID-19 drug target because it is suspected to enhance the ability of the virus to evade the human immune system. The SARS-CoV-2 Mac1 domain binds ADP-ribose and proteins harboring this important post-translational modification. Small molecules that bind the Mac1 domain in place of ADP-ribose might therefore be useful as molecular probes or scaffolds for antiviral drug discovery. Two high throughput screens were used here to identify such ligands in small libraries of drugs and drug-like compounds. The first screen used differential scanning fluorimetry (DSF, aka the thermal shift or ThermoFluor assay) to examine the melting temperature of SARS-CoV-2 Mac1 domain in the presence of various compounds. In the second screen, various high-resolution SARS-CoV-2 Mac1 structures were used with Autodock VINA to identify potential ligands. Numerous hit compounds were either steroids (estradiol valerate & flunisolide), beta-lactams (cefaclor & cefatrizine), or benzimidazoles (telmisartan, rabeprazole, omeprazole, & esomeprazole). Isothermal titration calorimetry was used to confirm that rabeprazole, omeprazole, and compounds in other chemical classes, such as irinotecan, nifedipine, trifluoperazine, bind SARS-CoV-2 Mac1 with an affinity similar to ADP-ribose.
    Keywords covid19
    Language English
    Publishing date 2020-07-06
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.07.06.190413
    Database COVID19

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  3. Article: Discovery of Drug-like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3.

    Virdi, Rajdeep S / Bavisotto, Robert V / Hopper, Nicholas C / Vuksanovic, Nemanja / Melkonian, Trevor R / Silvaggi, Nicholas R / Frick, David N

    bioRxiv : the preprint server for biology

    2020  

    Abstract: Small molecules that bind the SARS-CoV-2 non-structural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to coronavirus' ability to evade ... ...

    Abstract Small molecules that bind the SARS-CoV-2 non-structural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to coronavirus' ability to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, beta-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using Autodock VINA. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution.
    Keywords covid19
    Language English
    Publishing date 2020-09-01
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.07.06.190413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Discovery of Drug-Like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3.

    Virdi, Rajdeep S / Bavisotto, Robert V / Hopper, Nicholas C / Vuksanovic, Nemanja / Melkonian, Trevor R / Silvaggi, Nicholas R / Frick, David N

    SLAS discovery : advancing life sciences R & D

    2020  Volume 25, Issue 10, Page(s) 1162–1170

    Abstract: Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to ... ...

    Abstract Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, β-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using AutoDock Vina. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution.
    MeSH term(s) Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Binding Sites ; Coronavirus Papain-Like Proteases/chemistry ; Coronavirus Papain-Like Proteases/genetics ; Coronavirus Papain-Like Proteases/metabolism ; Cyclic AMP/chemistry ; Cyclic AMP/metabolism ; High-Throughput Screening Assays/methods ; Ligands ; Models, Molecular ; Molecular Docking Simulation ; Protein Conformation ; Protein Domains ; SARS-CoV-2/chemistry ; SARS-CoV-2/drug effects
    Chemical Substances Antiviral Agents ; Ligands ; Cyclic AMP (E0399OZS9N) ; Coronavirus Papain-Like Proteases (EC 3.4.22.2) ; papain-like protease, SARS-CoV-2 (EC 3.4.22.2)
    Keywords covid19
    Language English
    Publishing date 2020-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1177/2472555220960428
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4911: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  5. Article: Discovery of Drug-Like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3

    Virdi, Rajdeep S / Bavisotto, Robert V / Hopper, Nicholas C / Vuksanovic, Nemanja / Melkonian, Trevor R / Silvaggi, Nicholas R / Frick, David N

    SLAS Discov

    Abstract: Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to ... ...

    Abstract Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, ß-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using AutoDock Vina. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #800006
    Database COVID19

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  6. Article ; Online: Discovery of Drug-Like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3

    Virdi, Rajdeep S. / Bavisotto, Robert V. / Hopper, Nicholas C. / Vuksanovic, Nemanja / Melkonian, Trevor R. / Silvaggi, Nicholas R. / Frick, David N.

    SLAS DISCOVERY: Advancing the Science of Drug Discovery

    2020  , Page(s) 247255522096042

    Abstract: Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to ... ...

    Abstract Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, β-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using AutoDock Vina. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution.
    Keywords covid19
    Language English
    Publisher SAGE Publications
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1177/2472555220960428
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4911: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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