Insights on 3D Structures of Potential Drug-targeting Proteins of SARS-CoV-2: Application of Cavity Search and Molecular Docking.

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Tytuł:: Insights on 3D Structures of Potential Drug-targeting Proteins of SARS-CoV-2: Application of Cavity Search and Molecular Docking.
Autorzy:: Fernandes MS; Course of Pharmacy, Federal University of Pampa (UNIPAMPA)., BR 472, km 592, P.O. Box 118, 97500-970, Uruguaiana-RS, Brazil.
da Silva FS; Course of Pharmacy, Federal University of Pampa (UNIPAMPA)., BR 472, km 592, P.O. Box 118, 97500-970, Uruguaiana-RS, Brazil.
Freitas ACSG; Course of Pharmacy, Federal University of Pampa (UNIPAMPA)., BR 472, km 592, P.O. Box 118, 97500-970, Uruguaiana-RS, Brazil.
de Melo EB; Department of Pharmacy, State University of West Paraná (UNIOESTE)., Universitária Street 2069, 85819-110, Cascavel-PR, Brazil.
Trossini GHG; Department of Pharmacy, University of São Paulo (USP)., Lineu Prestes Avenue 580, 05508-900, São Paulo-SP, Brazil.
Paula FR; Course of Pharmacy, Federal University of Pampa (UNIPAMPA)., BR 472, km 592, P.O. Box 118, 97500-970, Uruguaiana-RS, Brazil.
Źródło:: Molecular informatics [Mol Inform] 2021 Feb; Vol. 40 (2), pp. e2000096. Date of Electronic Publication: 2020 Oct 20.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Weinheim, Germany : Wiley-VCH Verlag
MeSH Terms:: Molecular Docking Simulation*
COVID-19/*virology
SARS-CoV-2/*drug effects
Antiviral Agents/pharmacology ; Catalytic Domain ; Computer Simulation ; Coronavirus Nucleocapsid Proteins/chemistry ; Drug Design ; Humans ; Ligands ; Models, Molecular ; Phosphoproteins/chemistry ; Protein Binding ; Protein Conformation ; SARS-CoV-2/chemistry ; Spike Glycoprotein, Coronavirus/chemistry ; Viral Matrix Proteins/chemistry ; COVID-19 Drug Treatment
References:: N Engl J Med. 2003 May 15;348(20):1953-66. (PMID: 12690092)
Mol Inform. 2021 Feb;40(2):e2000096. (PMID: 32750187)
JAMA. 2020 Mar 17;323(11):1061-1069. (PMID: 32031570)
Nucleic Acids Res. 2018 Jul 2;46(W1):W374-W379. (PMID: 29750256)
N Engl J Med. 2020 Mar 5;382(10):929-936. (PMID: 32004427)
Adv Virus Res. 2011;81:85-164. (PMID: 22094080)
J Theor Biol. 2008 Oct 21;254(4):861-7. (PMID: 18706430)
Mol Inform. 2020 Aug;39(8):e2000028. (PMID: 32162456)
Protein Sci. 2020 Jul;29(7):1596-1605. (PMID: 32304108)
Science. 2020 Mar 13;367(6483):1260-1263. (PMID: 32075877)
Trials. 2020 Jan 3;21(1):8. (PMID: 31900204)
N Engl J Med. 2020 Feb 20;382(8):727-733. (PMID: 31978945)
N Engl J Med. 2012 Nov 8;367(19):1814-20. (PMID: 23075143)
J Comput Chem. 2009 Dec;30(16):2785-91. (PMID: 19399780)
J Chem Inf Model. 2013 Aug 26;53(8):2141-53. (PMID: 23834142)
Viruses. 2012 Jun;4(6):1011-33. (PMID: 22816037)
N Engl J Med. 2003 May 15;348(20):1967-76. (PMID: 12690091)
Thorax. 2004 Mar;59(3):252-6. (PMID: 14985565)
Cell Discov. 2020 Mar 18;6:16. (PMID: 32194981)
Infect Chemother. 2015 Sep;47(3):212-22. (PMID: 26483999)
Nat Rev Drug Discov. 2020 Mar;19(3):149-150. (PMID: 32127666)
mBio. 2018 Mar 6;9(2):. (PMID: 29511076)
Chem Phys Lett. 2020 Jul;750:137489. (PMID: 32313296)
Proteins. 2004 May 1;55(2):288-304. (PMID: 15048822)
Pharmgenomics Pers Med. 2014 Aug 14;7:241-9. (PMID: 25206310)
Nat Rev Microbiol. 2015 Jan;13(1):28-41. (PMID: 25417656)
Nat Biotechnol. 2007 Jan;25(1):71-5. (PMID: 17211405)
Trends Microbiol. 2016 Jun;24(6):490-502. (PMID: 27012512)
Nature. 2016 Mar 17;531(7594):381-5. (PMID: 26934220)
Science. 2020 Apr 24;368(6489):409-412. (PMID: 32198291)
Lancet. 2003 Oct 25;362(9393):1353-8. (PMID: 14585636)
Nat Commun. 2020 Jan 10;11(1):222. (PMID: 31924756)
Nat Rev Microbiol. 2019 Mar;17(3):181-192. (PMID: 30531947)
Lancet. 2020 Feb 15;395(10223):497-506. (PMID: 31986264)
Methods Mol Biol. 2015;1282:1-23. (PMID: 25720466)
Cell. 2018 Mar 8;172(6):1157-1159. (PMID: 29522735)
Cell Mol Immunol. 2020 Jul;17(7):765-767. (PMID: 32047258)
Antiviral Res. 2009 Jun;82(3):95-102. (PMID: 19428599)
Grant Information:: CAPES; 19/2551-0001784-7 FAPERGS; PDA-UNIPAMPA
Contributed Indexing:: Keywords: 3D Structures; COVID19; Cavity Search; Molecular Docking; SARS-CoV-2
Substance Nomenclature:: 0 (Antiviral Agents)
0 (Coronavirus Nucleocapsid Proteins)
0 (Ligands)
0 (Phosphoproteins)
0 (Spike Glycoprotein, Coronavirus)
0 (Viral Matrix Proteins)
0 (membrane protein, SARS-CoV-2)
0 (nucleocapsid phosphoprotein, SARS-CoV-2)
0 (spike protein, SARS-CoV-2)
Entry Date(s):: Date Created: 20200805 Date Completed: 20210216 Latest Revision: 20231103
Update Code:: 20240105
PubMed Central ID:: PMC7436870
DOI:: 10.1002/minf.202000096
PMID:: 32750187
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The emergence of the COVID-19 has caused public health problems worldwide and there is no effective pharmacological treatment for this disease. Research on 3D models of proteins and the search for active molecular sites are important tools to assist in the discovery of effective antiviral drugs to combat COVID-19. To address this problem, the 3D protein structures of SARS-CoV 2 were analyzed and submitted to cavities research, evaluation of their druggabillity and liganbility, and applied to molecular docking studies with potential ligand candidates actually assayed against COVID-19. Eight druggable potential cavity sites were determined in model structures' PDB code, 6W4B, 6VWW, 6W01, 6M3M, and 6VYO, and these are the good alternatives to be characterized as targets for antiviral compounds. The good cavity model of the protease 3D structure was used in molecular docking, and this allowed verifying the theoric interactions of this protein and lopinavir and ritonavir antiviral drugs. These results may assist in the use of 3D protein models in drug design studies aiming to develop drugs against the COVID-19 pandemic.
(© 2020 Wiley-VCH GmbH.)

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