Spectral entropy outperforms MS/MS dot product similarity for small-molecule compound identification

2021 ◽  
Author(s):  
Yuanyue Li ◽  
Tobias Kind ◽  
Jacob Folz ◽  
Arpana Vaniya ◽  
Sajjan Singh Mehta ◽  
...  
Keyword(s):  
Small Molecule ◽  
Spectral Entropy ◽  
Compound Identification ◽  
Small Molecule Compound ◽  
Dot Product

scholarly journals A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shin-ichiro Hattori ◽  
Nobuyo Higashi-Kuwata ◽  
Hironori Hayashi ◽  
Srinivasa Rao Allu ◽  
Jakka Raghavaiah ◽  
...  
Keyword(s):  
Small Molecule ◽  
Covalent Bond ◽  
Amino Acid Residues ◽  
X Ray ◽  
Viral Breakthrough ◽  
Main Protease ◽  
Small Molecule Compound ◽  
Polar Interactions ◽  
High Concentrations

AbstractExcept remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (Mpro). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 with EC50 values of 15 ± 4 and 4.2 ± 0.7 μM for GRL-1720 and 5h, respectively. Remdesivir permitted viral breakthrough at high concentrations; however, compound 5h completely blocks SARS-CoV-2 infection in vitro without viral breakthrough or detectable cytotoxicity. Combination of 5h and remdesivir exhibits synergism against SARS-CoV-2. Additional X-ray structural analysis show that 5h forms a covalent bond with Mpro and makes polar interactions with multiple active site amino acid residues. The present data suggest that 5h might serve as a lead Mpro inhibitor for the development of therapeutics for SARS-CoV-2 infection.

scholarly journals Expression of SSEA4 and TRA1-60 as Marker of Induced Pluripotent Stem Cells by Small Molecule Compound VC6TFZ on Peripheral Blood Mononuclear Cell

2020 ◽  
Author(s):  
A Andrianto ◽  
Adityo Basworo ◽  
Ivana Purnama Dewi ◽  
Budi Susetio Pikir
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Mononuclear Cells ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Induced Pluripotency ◽  
Small Molecule Compound ◽  
Induced Pluripotent

IntroductionIt is possible to induce pluripotent stem cells from somatic cells, offering an infinite cell resource with the potential for disease research and use in regenerative medicine. Due to ease of accessibility, minimum invasive treatment, and can be kept frozen, peripheral blood mononuclear cells (PBMC) were an attractive source cell. VC6TFZ, a small molecule compound, has been successfully reprogrammed from mouse fibroblast induced pluripotent stem cells (iPSCs). However, it has not been confirmed in humans.ObjectiveThe aim of this research is to determine whether the small molecule compound VC6TFZ can induced pluripotency of PBMC to generate iPSCs detected with expression of SSEA4 and TRA1-60.MethodsUsing the centrifugation gradient density process, mononuclear cells were separated from peripheral venous blood. Mononuclear cells were cultured for 6 days in the expansion medium. The cells were divided into four groups; group 1 (P1), which was not exposed to small molecules (control group) and groups 2-4 (P2-P4), the experimental groups, subjected to various dosages of the small molecule compound VC6TFZ (VPA, CHIR, Tranylcypromine, FSK, Dznep, and TTNPB). The induction of pluripotency using small molecule compound VC6TFZ was completed within 14 days, then for 7 days the medium shifted to 2i medium. iPSCs identification in based on colony morphology and pluripotent gene expression, SSEA4 and TRA1-60 marker, using immunocytochemistry.ResultsColonies appeared on reprogramming process in day 7th. These colonies had round, large, and cobble stone morphology like ESC. Gene expression of SSEA4 and TRA 1-60 increased statisticaly significant than control group (SSEA4 were P2 p=0.007; P3 p=0.001; P4 p=0.009 and TRA 1-60 were P2 p=0.002; P3 p=0.001; P4 p=0.001).ConclusionSmall molecule compound VC6TFZ could induced pluripotency of human PBMC to generate iPSCs. Pluripotxency marker gene expression, SSEA 4 and TRA 1-60, in the experimental group was statistically significantly higher than in the control group.

scholarly journals pH-Induced Activation of Arenavirus Membrane Fusion Is Antagonized by Small-Molecule Inhibitors

2008 ◽  
Vol 82 (21) ◽  
pp. 10932-10939 ◽  
Author(s):  
Joanne York ◽  
Dongcheng Dai ◽  
Sean M. Amberg ◽  
Jack H. Nunberg
Keyword(s):  
Membrane Fusion ◽  
Small Molecule ◽  
Viral Entry ◽  
De Novo ◽  
Lassa Fever ◽  
Molecular Target ◽  
Active Inhibitor ◽  
Hemorrhagic Fevers ◽  
Lassa Fever Virus ◽  
Small Molecule Compound

ABSTRACT The arenavirus envelope glycoprotein (GPC) mediates viral entry through pH-induced membrane fusion in the endosome. This crucial process in the viral life cycle can be specifically inhibited in the New World arenaviruses by the small-molecule compound ST-294. Here, we show that ST-294 interferes with GPC-mediated membrane fusion by targeting the interaction of the G2 fusion subunit with the stable signal peptide (SSP). We demonstrate that amino acid substitutions at lysine-33 of the Junín virus SSP confer resistance to ST-294 and engender de novo sensitivity to ST-161, a chemically distinct inhibitor of the Old World Lassa fever virus. These compounds, as well as a broadly active inhibitor, ST-193, likely share a molecular target at the SSP-G2 interface. We also show that both ST-294 and ST-193 inhibit pH-induced dissociation of the G1 receptor-binding subunit from GPC, a process concomitant with fusion activation. Interestingly, the inhibitory activity of these molecules can in some cases be overcome by further lowering the pH used for activation. Our results suggest that these small molecules act to stabilize the prefusion GPC complex against acidic pH. The pH-sensitive interaction between SSP and G2 in GPC represents a robust molecular target for the development of antiviral compounds for the treatment of arenavirus hemorrhagic fevers.

A new small-molecule compound, Q308, silences latent HIV-1 provirus by suppressing Tat- and FACT-mediated transcription

2021 ◽  
Author(s):  
Chen-liang Zhou ◽  
Yi-fan Huang ◽  
Yi-bin Li ◽  
Tai-zhen Liang ◽  
Teng-yi Zheng ◽  
...  
Keyword(s):  
Small Molecule ◽  
Difficult Problem ◽  
Viral Reservoir ◽  
Functional Cure ◽  
Latently Infected ◽  
Small Molecule Compound ◽  
Infected Cells ◽  
Latent Hiv ◽  
Anti Hiv ◽  
Hiv 1

Eliminating the latent HIV reservoir remains a difficult problem for creating an HIV functional cure or achieving remission. The “block-and-lock” strategy aims to steadily suppress transcription of the viral reservoir and lock the HIV promoter in deep latency using latency-promoting agents (LPAs). However, to date, most of the investigated LPA candidates are not available for clinical trials, and some of them exhibit immune-related adverse reactions. The discovery and development of new, active, and safe LPA candidates for an HIV cure are necessary to eliminate residual HIV-1 viremia through the “block-and-lock” strategy. In this study, we demonstrated that a new small-molecule compound, Q308, silenced the HIV-1 provirus by inhibiting Tat-mediated gene transcription and selectively downregulating the expression levels of the facilitated chromatin transcription (FACT) complex. Strikingly, Q308 induced the preferential apoptosis in HIV-1 latently infected cells, indicating that Q308 may reduce the size of the viral reservoir and thus further prevent viral rebound. These findings highlight that Q308 is a novel and safe anti-HIV-1 inhibitor candidate for a functional cure.

Crystal aggregation into periodically grating-banded assemblies in phthalic acid modulated by molten poly(ethylene oxide)

CrystEngComm ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 467-477 ◽  
Author(s):  
Tzu-Yu Chen ◽  
Eamor M. Woo ◽  
Selvaraj Nagarajan
Keyword(s):  
Ethylene Oxide ◽  
Small Molecule ◽  
Phthalic Acid ◽  
Ordered Structures ◽  
Crystal Aggregation ◽  
Banded Spherulites ◽  
Small Molecule Compound ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene

A small-molecule compound, phthalic acid (PA), crystallized in the presence of poly(ethylene oxide) (PEO) with various compositions was utilized as a model to investigate the morphology and crystal assembly of periodically ordered structures in banded spherulites.

scholarly journals EC330, a small-molecule compound, is a potential novel inhibitor of LIF signaling

2020 ◽  
Vol 12 (6) ◽  
pp. 477-480
Author(s):  
Xuetian Yue ◽  
Fangnan Wu ◽  
Jianming Wang ◽  
Kaitlin Kim ◽  
Bindu Santhamma ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Compound
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