2 research outputs found
Data_Sheet_1_Niclosamide as a chemical probe for analyzing SARS-CoV-2 modulation of host cell lipid metabolism.zip
IntroductionSARS-CoV-2 subverts host cell processes to facilitate rapid replication and dissemination, and this leads to pathological inflammation.MethodsWe used niclosamide (NIC), a poorly soluble anti-helminth drug identified initially for repurposed treatment of COVID-19, which activates the cells’ autophagic and lipophagic processes as a chemical probe to determine if it can modulate the host cell’s total lipid profile that would otherwise be either amplified or reduced during SARS-CoV-2 infection.ResultsThrough parallel lipidomic and transcriptomic analyses we observed massive reorganization of lipid profiles of SARS-CoV-2 infected Vero E6 cells, especially with triglycerides, which were elevated early during virus replication, but decreased thereafter, as well as plasmalogens, which were elevated at later timepoints during virus replication, but were also elevated under normal cell growth. These findings suggested a complex interplay of lipid profile reorganization involving plasmalogen metabolism. We also observed that NIC treatment of both low and high viral loads does not affect virus entry. Instead, NIC treatment reduced the abundance of plasmalogens, diacylglycerides, and ceramides, which we found elevated during virus infection in the absence of NIC, resulting in a significant reduction in the production of infectious virions. Unexpectedly, at higher viral loads, NIC treatment also resulted in elevated triglyceride levels, and induced significant changes in phospholipid metabolism.DiscussionWe posit that future screens of approved or new partner drugs should prioritize compounds that effectively counter SARS-CoV-2 subversion of lipid metabolism, thereby reducing virus replication, egress, and the subsequent regulation of key lipid mediators of pathological inflammation.</p
Expanding Per- and Polyfluoroalkyl Substances Coverage in Nontargeted Analysis Using Data-Independent Analysis and IonDecon
Per- and polyfluoroalkyl substances (PFAS) are widespread,
persistent
environmental contaminants that have been linked to various health
issues. Comprehensive PFAS analysis often relies on ultra-high-performance
liquid chromatography coupled with high-resolution mass spectrometry
(UHPLC HRMS) and molecular fragmentation (MS/MS). However, the selection
and fragmentation of ions for MS/MS analysis using data-dependent
analysis results in only the topmost abundant ions being selected.
To overcome these limitations, All Ions fragmentation (AIF) can be
used alongside data-dependent analysis. In AIF, ions across the entire m/z range are simultaneously fragmented;
hence, precursor–fragment relationships are lost, leading to
a high false positive rate. We introduce IonDecon, which filters All
Ions data to only those fragments correlating with precursor ions.
This software can be used to deconvolute any All Ions files and generates
an open source DDA formatted file, which can be used in any downstream
nontargeted analysis workflow. In a neat solution, annotation of PFAS
standards using IonDecon and All Ions had the exact same false positive
rate as when using DDA; this suggests accurate annotation using All
Ions and IonDecon. Furthermore, deconvoluted All Ions spectra retained
the most abundant peaks also observed in DDA, while filtering out
much of the artifact peaks. In complex samples, incorporating AIF
and IonDecon into workflows can enhance the MS/MS coverage of PFAS
(more than tripling the number of annotations in domestic sewage).
Deconvolution in complex samples of All Ions data using IonDecon did
retain some false fragments (fragments not observed when using ion
selection, which were not isotopes or multimers), and therefore DDA
and intelligent acquisition methods should still be acquired when
possible alongside All Ions to decrease the false positive rate. Increased
coverage of PFAS can inform on the development of regulations to address
the entire PFAS problem, including both legacy and newly discovered
PFAS