Abstract:The first corona-pandemic, coronavirus disease 2019 (COVID-19) caused a huge health crisis and incalculable damage worldwide. Knowledge of how to cure the disease is urgently needed. Emerging immune escaping mutants of the virus suggested that it may be potentially persistent in human society as a regular health threat as the flu virus. Therefore, it is imperative to identify appropriate biomarkers to indicate pathological and physiological states, and more importantly, clinic outcomes. Proteins are the perfor… Show more
“…Among these were two types of N-linked glycosylation: HexNAc(1)dHex (2) [N] was up in control (Figure 4, middle), and HexNAc [N], was up in bottom). Notably, changes in glycosylation were previously observed on the viral SARS-CoV-2 proteins during COVID-19 (Praissman and Wells, 2021;Reis et al, 2021;Shajahan et al, 2021;Zhong et al, 2021), even though such changes in the host organism, to the best of our knowledge, were not previously reported. Additional modifications on this list were detected at very low levels.…”
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus of the coronavirus family that causes coronavirus disease-19 (COVID-19) in humans and a number of animal species. COVID-19 has rapidly propagated in the world in the past 2 years, causing a global pandemic. Here, we performed proteomic analysis of plasma samples from COVID-19 patients compared to healthy control donors in an exploratory study to gain insights into protein-level changes in the patients caused by SARS-CoV-2 infection and to identify potential proteomic and posttranslational signatures of this disease. Our results suggest a global change in protein processing and regulation that occurs in response to SARS-CoV-2, and the existence of a posttranslational COVID-19 signature that includes an elevation in threonine phosphorylation, a change in glycosylation, and a decrease in arginylation, an emerging posttranslational modification not previously implicated in infectious disease. This study provides a resource for COVID-19 researchers and, longer term, and will inform our understanding of this disease and its treatment.
“…Among these were two types of N-linked glycosylation: HexNAc(1)dHex (2) [N] was up in control (Figure 4, middle), and HexNAc [N], was up in bottom). Notably, changes in glycosylation were previously observed on the viral SARS-CoV-2 proteins during COVID-19 (Praissman and Wells, 2021;Reis et al, 2021;Shajahan et al, 2021;Zhong et al, 2021), even though such changes in the host organism, to the best of our knowledge, were not previously reported. Additional modifications on this list were detected at very low levels.…”
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus of the coronavirus family that causes coronavirus disease-19 (COVID-19) in humans and a number of animal species. COVID-19 has rapidly propagated in the world in the past 2 years, causing a global pandemic. Here, we performed proteomic analysis of plasma samples from COVID-19 patients compared to healthy control donors in an exploratory study to gain insights into protein-level changes in the patients caused by SARS-CoV-2 infection and to identify potential proteomic and posttranslational signatures of this disease. Our results suggest a global change in protein processing and regulation that occurs in response to SARS-CoV-2, and the existence of a posttranslational COVID-19 signature that includes an elevation in threonine phosphorylation, a change in glycosylation, and a decrease in arginylation, an emerging posttranslational modification not previously implicated in infectious disease. This study provides a resource for COVID-19 researchers and, longer term, and will inform our understanding of this disease and its treatment.
“…Among these were three types of glycosylation (N-linked up in controls, and S-linked and N-terminal up in COVID-19). Notably, changes in glycosylation were previously observed on the viral SARS-CoV-2 proteins during COVID-19 [26][27][28][29] , even though such changes in the host organism, to the best of our knowledge, were not previously reported. Additional modifications on this list were detected at very low levels.…”
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus of the coronavirus family that causes coronavirus disease-19 (COVID-19) in humans and a number of animal species. COVID-19 has rapidly propagated in the world in the past 2 years, causing a global pandemic. Here, we performed proteomic analysis of plasma samples from COVID-19 patients compared to healthy control donors in an exploratory study to gain insights into protein-level changes in the patients caused by SARS-CoV-2 infection and to identify potential proteomic and posttranslational signatures of this disease. Our results suggest a global change in protein processing and regulation that occurs in response to SARS-CoV-2, and the existence of a posttranslational COVID-19 signature that includes an elevation in threonine phosphorylation, a change in glycosylation, and a decrease in arginylation, an emerging posttranslational modification not previously implicated in infectious disease. This study provides a resource for COVID-19 researchers and, longer term, will inform our understanding of this disease and its treatment.Key PointsPlasma from COVID-19 patients exhibits prominent protein- and peptide-level changesProteins from COVID-19 patient plasma exhibit prominent changes in several key posttranslational modifications
“…The in silico data of the selected peptides were then compared with the literature data. 16 , 21 , 22 , 29 Peptides defined by Skyline analysis monitored for each protein are reported in the Supporting Information Table ST2 . This method contained a total of 77 peptides and 407 precursor ion–daughter ions transitions associated with the peptides selected from the defined target proteins that constitute the protein signature of CoV-2 as reported in Table ST2 .…”
Section: Results
and Discussionmentioning
confidence: 99%
“…A number of unique peptides belonging to each target protein were then defined on the basis of their mass spectrometric behavior together with their specific precursor ion–product ion transitions as defined by their unique amino acid sequence by in silico analysis using the Skyline software. The in silico data of the selected peptides were then compared with the literature data. ,,, Peptides defined by Skyline analysis monitored for each protein are reported in the Supporting Information Table ST2. This method contained a total of 77 peptides and 407 precursor ion–daughter ions transitions associated with the peptides selected from the defined target proteins that constitute the protein signature of CoV-2 as reported in Table ST2.…”
Numerous reverse
transcription polymerase chain reaction (RT-PCR)
tests have emerged over the past year as the gold standard for detecting
millions of cases of SARS-CoV-2 reported daily worldwide. However,
problems with critical shortages of key reagents such as PCR primers
and RNA extraction kits and unpredictable test reliability related
to high viral replication cycles have triggered the need for alternative
methodologies to PCR to detect specific COVID-19 proteins. Several
authors have developed methods based on liquid chromatography with
tandem mass spectrometry (LC–MS/MS) to confirm the potential
of the technique to detect two major proteins, the spike and the nucleoprotein,
of COVID-19. In the present work, an S-Trap mini spin column digestion
protocol was used for sample preparation prodromal to LC–MS/MS
analysis in multiple reactions monitoring ion mode (MRM) to obtain
a comprehensive method capable of detecting different viral proteins.
The developed method was applied to n. 81 oro/nasopharyngeal swabs
submitted in parallel to quantitative reverse transcription PCR (RT-qPCR)
assays to detect RdRP, the S and N genes specific for COVID-19, and
the E gene for all
Sarbecoviruses
, including SARS-CoV-2
(with cycle negativity threshold set to 40). A total of 23 peptides
representative of the six specific viral proteins were detected in
the monitoring of 128 transitions found to have good ionic currents
extracted in clinical samples that reacted differently to the PCR
assay. The best instrumental response came from the FLPFQFGR sequence
of spike [558−566] peptide used to test the analytical performance
of the method that has good sensitivity with a low false-negative
rate. Transition monitoring using a targeted MS approach has the great
potential to detect the fragmentation reactions of any peptide molecularly
defined by a specific amino acid sequence, offering the extensibility
of the approach to any viral sequence including derived variants and
thus providing insights into the development of new types of clinical
diagnostics.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.