% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{HernndezGonzlez:909091,
author = {Hernández González, Jorge E. and Eberle, Raphael J. and
Willbold, Dieter and Coronado, Mônika A.},
title = {{A} {C}omputer-{A}ided {A}pproach for the {D}iscovery of
{D}-{P}eptides as {I}nhibitors of {SARS}-{C}o{V}-2 {M}ain
{P}rotease},
journal = {Frontiers in molecular biosciences},
volume = {8},
issn = {2296-889X},
address = {Lausanne},
publisher = {Frontiers},
reportid = {FZJ-2022-03004},
pages = {816166},
year = {2022},
abstract = {The SARS-CoV-2 main protease, also known as
3-chymotrypsin-like protease (3CLpro), is a cysteine
protease responsible for the cleavage of viral polyproteins
pp1a and pp1ab, at least, at eleven conserved sites, which
leads to the formation of mature nonstructural proteins
essential for the replication of the virus. Due to its
essential role, numerous studies have been conducted so far,
which have confirmed 3CLpro as an attractive drug target to
combat Covid-19 and have reported a vast number of
inhibitors and their co-crystal structures. Despite all the
ongoing efforts, D-peptides, which possess key advantages
over L-peptides as therapeutic agents, have not been
explored as potential drug candidates against 3CLpro. The
current work fills this gap by reporting an in silico
approach for the discovery of D-peptides capable of
inhibiting 3CLpro that involves structure-based virtual
screening (SBVS) of an in-house library of D-tripeptides and
D-tetrapeptides into the protease active site and subsequent
rescoring steps, including Molecular Mechanics
Generalized-Born Surface Area (MM-GBSA) free energy
calculations and molecular dynamics (MD) simulations. In
vitro enzymatic assays conducted for the four top-scoring
D-tetrapeptides at 20 μM showed that all of them caused
$55-85\%$ inhibition of 3CLpro activity, thus highlighting
the suitability of the devised approach. Overall, our
results present a promising computational strategy to
identify D-peptides capable of inhibiting 3CLpro, with
broader application in problems involving protein
inhibition.},
cin = {IBI-7},
ddc = {570},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {35187076},
UT = {WOS:000759912700001},
doi = {10.3389/fmolb.2021.816166},
url = {https://juser.fz-juelich.de/record/909091},
}