Evaluation of Variant-Specific Peptides for Detection of SARS-CoV-2 Variants of Concern.

Evaluation of Variant-Specific Peptides for Detection of SARS-CoV-2 Variants of Concern.
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DOI:
10.1021/acs.jproteome.2c00325
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发表时间:
2022-10-07
影响因子:
4.4
通讯作者:
Timperman, AaronT.
Timperman, AaronT.
中科院分区:
生物学2区
文献类型:
--
作者:
Suddhapas, Kantaphon;Choi, M. Hannah;Shortreed, Michael R.;Timperman, AaronT.

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SARS-CoV-2 omicron变种对全球抗击这一流行病的努力提出了重大挑战。预计SARS-CoV-2在可预见的未来仍将流行,因此识别SARS-CoV-2变体的能力对于理解和控制大流行至关重要。主要的变异发现方法,基因组测序,是耗时的,不敏感的,和昂贵的。超高效液相色谱-质谱法(UPLC-MS)提供了一种令人兴奋的替代检测模式,前提是含有变体的肽标记物可从其串联质谱(MS/MS)中充分检测。我们合成了SARS-CoV-2变体α,β,γ,δ和Omicron的模型胰蛋白酶肽,并评估了它们的信号强度,HCD光谱,反相保留时间。对于蛋白质型肽的分子离子:β(QIAPGQTGNIADYNYK)、γ(TQLPSAYTNSFTR)、δ(VGGNYR)和Omicron(TLVKQLSSK),从纯溶液中获得的检测限为781、781、65和65 μ g。这些检测限与先前报道的来自SARS-CoV-2刺突蛋白的蛋白型肽HTPINLVR的检测限相当。这项研究证明了通过其蛋白质型肽区分SARS-CoV-2变体的潜力,该方法广泛适用于各种病原体。
The SARS-CoV-2 omicron variant presented significant challenges to the global effort to counter the pandemic. SARS-CoV-2 is predicted to remain prevalent for the foreseeable future, making the ability to identify SARS-CoV-2 variants imperative in understanding and controlling the pandemic. The predominant variant discovery method, genome sequencing, is time-consuming, insensitive, and expensive. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) offers an exciting alternative detection modality provided that variant-containing peptide markers are sufficiently detectable from their tandem mass spectra (MS/MS). We have synthesized model tryptic peptides of SARS-CoV-2 variants alpha, beta, gamma, delta, and omicron and evaluated their signal intensity, HCD spectra, reverse phase retention time. Detection limits of 781, 781, 65, and 65 amol are obtained for the molecular ions of the proteotypic peptides: beta (QIAPGQTGNIADYNYK), gamma (TQLPSAYTNSFTR), delta (VGGNYNYR), and omicron (TLVKQLSSK), from neat solutions. These detection limits are on par with the detection limits of a previously reported proteotypic peptide from the SARS-CoV-2 spike protein, HTPINLVR. This study demonstrates the potential to differentiate SARS-CoV-2 variants through their proteotypic peptides with an approach that is broadly applicable across a wide range of pathogens.
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