Inhibition of SARS-CoV-2 replication by zinc gluconate in combination with hinokitiol.
Enzyme inhibition
Ionophore
Protease activity
Protein structure
SARS-CoV-2
Zinc gluconate
Journal
Journal of inorganic biochemistry
ISSN: 1873-3344
Titre abrégé: J Inorg Biochem
Pays: United States
ID NLM: 7905788
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
19
01
2022
revised:
18
02
2022
accepted:
22
02
2022
pubmed:
8
3
2022
medline:
14
4
2022
entrez:
7
3
2022
Statut:
ppublish
Résumé
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is currently the major challenge to global public health. Two proteases, papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro or Mpro), are indispensable for SARS-CoV-2 replication, making them attractive targets for antiviral therapy development. Here we screened a panel of essential metal ions using a proteolytic assay and identified that zinc gluconate, a widely-used zinc supplement, strongly inhibited the proteolytic activities of the two proteases in vitro. Biochemical and crystallographic data reveal that zinc gluconate exhibited the inhibitory function via binding to the protease catalytic site residues. We further show that treatment of zinc gluconate in combination with a small molecule ionophore hinokitiol, could lead to elevated intracellular Zn
Identifiants
pubmed: 35255411
pii: S0162-0134(22)00066-6
doi: 10.1016/j.jinorgbio.2022.111777
pmc: PMC8886686
pii:
doi:
Substances chimiques
Antiviral Agents
0
Gluconates
0
Monoterpenes
0
Tropolone
7L6DL16P1T
Peptide Hydrolases
EC 3.4.-
Zinc
J41CSQ7QDS
gluconic acid
R4R8J0Q44B
beta-thujaplicin
U5335D6EBI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111777Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Références
Cell Host Microbe. 2011 Sep 15;10(3):248-59
pubmed: 21925112
Metallomics. 2015 Feb;7(2):202-11
pubmed: 25362967
Chemistry. 2020 Nov 26;26(66):15140-15144
pubmed: 32915473
Science. 2020 Apr 24;368(6489):409-412
pubmed: 32198291
Biochemistry. 2005 Aug 2;44(30):10349-59
pubmed: 16042412
Nat Struct Mol Biol. 2020 Jun;27(6):529-532
pubmed: 32382072
Nature. 2020 Jun;582(7811):289-293
pubmed: 32272481
Immunity. 2013 Oct 17;39(4):697-710
pubmed: 24138881
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Chem Commun (Camb). 2021 Aug 10;57(64):7910-7913
pubmed: 34278402
FEBS J. 2014 Sep;281(18):4085-96
pubmed: 25039866
Nutrients. 2021 Feb 09;13(2):
pubmed: 33572045
Immunity. 2018 Apr 17;48(4):675-687.e7
pubmed: 29653696
Trends Immunol. 2007 Jan;28(1):1-4
pubmed: 17126599
J Am Chem Soc. 2020 Dec 30;142(52):21883-21890
pubmed: 33320670
J Am Chem Soc. 2007 Sep 5;129(35):10911-21
pubmed: 17696343
Nat Microbiol. 2020 Nov;5(11):1439-1448
pubmed: 33028965
Dalton Trans. 2021 Sep 14;50(35):12226-12233
pubmed: 34396374
J Cell Biol. 2007 May 21;177(4):637-45
pubmed: 17502426
Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5717-22
pubmed: 16581910
Biometals. 2001 Sep-Dec;14(3-4):315-30
pubmed: 11831462
Chem Sci. 2021 Sep 24;12(42):14098-14102
pubmed: 34760193
Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1419-41
pubmed: 16987000
Angew Chem Int Ed Engl. 2021 May 3;60(19):10716-10723
pubmed: 33606889
J Virol. 2009 Jan;83(1):58-64
pubmed: 18922875
Chem Commun (Camb). 2021 Sep 30;57(78):10083-10086
pubmed: 34514483
Science. 2017 May 12;356(6338):608-616
pubmed: 28495746
J Trace Elem Med Biol. 2021 Dec;68:126818
pubmed: 34274845
Nature. 2009 Aug 13;460(7257):823-30
pubmed: 19675642