About: GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection

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About: GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection Goto Sponge NotDistinct Permalink

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection
Creator	Okamura, Tadashi Takamatsu, Yuki Davis, David Ghosh, Arun Richman, Douglas Bulut, Haydar Das, Debananda Hattori, Shin-Ichiro Higshi-Kuwata, Nobuyo Kishimoto, Naoki Maeda, Kenji Matsuda, Kouki Mitsuya, Hiroaki Misumi, Shogo Raghavaiah, Jakka Takamune, Nobutoki Yarchoan, Robert
Source	Medline; PMC
abstract	We assessed various newly generated compounds that target the main protease (M(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and various previously known compounds reportedly active against SARS-CoV-2, employing RNA quantitative PCR (RNA-qPCR), cytopathicity assays, and immunocytochemistry. Here, we show that two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, exerted potent activity against SARS-CoV-2 in cell-based assays performed using VeroE6 cells and TMPRSS2-overexpressing VeroE6 cells. While GRL-0820 and the nucleotide analog remdesivir blocked SARS-CoV-2 infection, viral breakthrough occurred. No significant anti-SARS-CoV-2 activity was found for several compounds reportedly active against SARS-CoV-2 such as lopinavir, nelfinavir, nitazoxanide, favipiravir, and hydroxychroloquine. In contrast, GRL-0920 exerted potent activity against SARS-CoV-2 (50% effective concentration [EC(50)] = 2.8 μM) and dramatically reduced the infectivity, replication, and cytopathic effect of SARS-CoV-2 without significant toxicity as examined with immunocytochemistry. Structural modeling shows that indole and chloropyridinyl of the derivatives interact with two catalytic dyad residues of M(pro), Cys145 and His41, resulting in covalent bonding, which was verified using high-performance liquid chromatography–mass spectrometry (HPLC/MS), suggesting that the indole moiety is critical for the anti-SARS-CoV-2 activity of the derivatives. GRL-0920 might serve as a potential therapeutic for coronavirus disease 2019 (COVID-19) and might be optimized to generate more-potent anti-SARS-CoV-2 compounds.
has issue date	2020-08-20(xsd:dateTime)
bibo:doi	10.1128/mbio.01833-20
bibo:pmid	32820005
has license	no-cc
sha1sum (hex)	e4edf962755cc4073e1ed12a48b1dbd9deab31d0
schema:url	https://doi.org/10.1128/mbio.01833-20
resource representing a document's title	GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection
has PubMed Central identifier	PMC7441487
has PubMed identifier	32820005
schema:publication	mBio
resource representing a document's body	covid:e4edf962755cc4073e1ed12a48b1dbd9deab31d0#body_text
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