Imperial College London
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DrElenaChekmeneva

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Research Associate - Structural Elucidation
 
 
 
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e.chekmeneva

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mehta:2022:10.1016/j.medj.2022.01.009,
author = {Mehta, R and Chekmeneva, E and Jackson, H and Sands, C and Mills, E and Arancon, D and Li, HK and Arkell, P and Rawson, T and Hammond, R and Amran, M and Haber, A and Cooke, G and Noursadeghi, M and Kaforou, M and Lewis, M and Takats, Z and Sriskandan, S},
doi = {10.1016/j.medj.2022.01.009},
journal = {Med},
pages = {204--215.e6},
title = {Antiviral metabolite 3’-Deoxy-3’,4’-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19},
url = {http://dx.doi.org/10.1016/j.medj.2022.01.009},
volume = {3},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:There is a critical need for rapid viral infection diagnostics to enable prompt case identification in pandemic settings and support targeted antimicrobial prescribing.Methods:Using untargeted high-resolution liquid chromatography coupled with mass spectrometry, we compared the admission serum metabolome of emergency department patients with viral infections including COVID-19, bacterial infections, inflammatory conditions, and healthy controls. Sera from an independent cohort of emergency department patients admitted with viral or bacterial infections underwent profiling to validate findings. Associations between whole-blood gene expression and the identified metabolite of interest were examined.Findings:3'-Deoxy-3',4'-didehydro-cytidine (ddhC), a free base of the only known human antiviral small molecule ddhC-triphosphate (ddhCTP), was detected for the first time in serum. When comparing 60 viral to 101 non-viral cases in the discovery cohort, ddhC was the most differentially abundant metabolite, generating an area under the receiver operating characteristic curve (AUC) of 0.954 (95% CI: 0.923-0.986). In the validation cohort, ddhC was again the most significantly differentially abundant metabolite when comparing 40 viral to 40 bacterial cases, generating an AUC of 0.81 (95% CI 0.708-0.915). Transcripts of viperin and CMPK2, enzymes responsible for ddhCTP synthesis, were amongst the five genes most highly correlated to ddhC abundance.Conclusions:The antiviral precursor molecule ddhC is detectable in serum and an accurate marker for acute viral infection. Interferon-inducible genes viperin and CMPK2 are implicated in ddhC production in vivo. These findings highlight a future diagnostic role for ddhC in viral diagnosis, pandemic preparedness, and acute infection management.
AU  - Mehta,R
AU  - Chekmeneva,E
AU  - Jackson,H
AU  - Sands,C
AU  - Mills,E
AU  - Arancon,D
AU  - Li,HK
AU  - Arkell,P
AU  - Rawson,T
AU  - Hammond,R
AU  - Amran,M
AU  - Haber,A
AU  - Cooke,G
AU  - Noursadeghi,M
AU  - Kaforou,M
AU  - Lewis,M
AU  - Takats,Z
AU  - Sriskandan,S
DO  - 10.1016/j.medj.2022.01.009
EP  - 215
PY  - 2022///
SN  - 2666-6340
SP  - 204
TI  - Antiviral metabolite 3’-Deoxy-3’,4’-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19
T2  - Med
UR  - http://dx.doi.org/10.1016/j.medj.2022.01.009
UR  - https://www.sciencedirect.com/science/article/pii/S2666634022000447?via%3Dihub
UR  - http://hdl.handle.net/10044/1/94024
VL  - 3
ER  -
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