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@ARTICLE{Eberle:892431,
author = {Eberle, Raphael and Olivier, Danilo S. and Amaral, Marcos
S. and Gering, Ian and Willbold, Dieter and Arni, Raghuvir
K. and Coronado, Monika A.},
title = {{T}he {R}epurposed {D}rugs {S}uramin and {Q}uinacrine
{C}ooperatively {I}nhibit {SARS}-{C}o{V}-2 3{CL}pro {I}n
{V}itro},
journal = {Viruses},
volume = {13},
number = {5},
issn = {1999-4915},
address = {Basel},
publisher = {MDPI},
reportid = {FZJ-2021-02077},
pages = {873 -},
year = {2021},
abstract = {Since the first report of a new pneumonia disease in
December 2019 (Wuhan, China) the WHO reported more than 148
million confirmed cases and 3.1 million losses globally up
to now. The causative agent of COVID-19 (SARS-CoV-2) has
spread worldwide, resulting in a pandemic of unprecedented
magnitude. To date, several clinically safe and efficient
vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson $\&$
Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs
for emergency use have been approved. However, increasing
numbers of SARS-Cov-2 variants make it imminent to identify
an alternative way to treat SARS-CoV-2 infections. A
well-known strategy to identify molecules with inhibitory
potential against SARS-CoV-2 proteins is repurposing
clinically developed drugs, e.g., antiparasitic drugs. The
results described in this study demonstrated the inhibitory
potential of quinacrine and suramin against SARS-CoV-2 main
protease (3CLpro). Quinacrine and suramin molecules
presented a competitive and noncompetitive inhibition mode,
respectively, with IC50 values in the low micromolar range.
Surface plasmon resonance (SPR) experiments demonstrated
that quinacrine and suramin alone possessed a moderate or
weak affinity with SARS-CoV-2 3CLpro but suramin binding
increased quinacrine interaction by around a factor of
eight. Using docking and molecular dynamics simulations, we
identified a possible binding mode and the amino acids
involved in these interactions. Our results suggested that
suramin, in combination with quinacrine, showed promising
synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We
suppose that the identification of effective, synergistic
drug combinations could lead to the design of better
treatments for the COVID-19 disease and repurposable drug
candidates offer fast therapeutic breakthroughs, mainly in a
pandemic moment.},
cin = {IBI-7},
ddc = {050},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34068686},
UT = {WOS:000654617600001},
doi = {10.3390/v13050873},
url = {https://juser.fz-juelich.de/record/892431},
}