Reference : UMR6230-ARNTES-010
Workplace : NANTES
Date of publication : Thursday, May 5, 2022
Scientific Responsible name : Arnaud Tessier
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 15 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Since the beginning of the COVID‐19 pandemic, there have been more than 6 million deaths in the
world. The current pandemic reminds us of our vulnerability to viruses, especially
emerging RNA viruses (SARS‐CoV, MERS, SARS‐CoV‐2, Zika, Dengue, Chikungunya, Ebola, etc.). As examplified by nucleosides such as remdesevir or ribavirin, this family of compounds
represents in this fight, more than half of the antivirals on the market. In this context, our
research program plans to design and evaluate new antivirals against these viruses
emerging. The objective of this PhD thesis is part of a rational approach for the design and
the development of original nucleoside analogues within a national GAVO program
(Generation of Original Antivirals). In support of this work, the biological evaluation of these analogues
originals on a large panel of viruses, will be carried out by a consortium of virologists and biologists
Based on the model of C‐nucleoside Remdesivir and based on the expertise of our team on the
synthesis of nucleoside analogues, the work of the PhD student will be focused on
the development of the 1 'position of natural nucleosides to lead to a generation of new
antivirals. For this, one of the objectives in this first phase of the PhD thesis will aim to provide
a variety of original chemical modifications, from key saccharide precursors having teir synthesis already validated in our hand.1 Thus, via this synthesis strategy that we master, a
series of C-nucleosides comprising original nucleobases will be targeted in order to evaluate new
original analogs of remdesivir, not accessible by current synthetic strategies.
The inhibitory activity of new nucleoside candidates against viral strains
available on the platforms of the ViroCrib consortium, will be evaluated in parallel with the synthesis to
establish relevant pharmacomodulation elements.
These results can be analyzed and interpreted within the GAVO consortium thanks to the contribution of bioinformaticinas specialized in the targeted
protein of interest.2 On the other hand, the introduction of relevant functional groups in position
5' du ribose will complete this PhD thesis project and will also aim to produce prodrugs of
nucleosides as new and more efficient derivatives, in order to consider their evaluation in cellulo
or in vivo.
1 Synthesis of novel C‐nucleoside analogues bearing an anomeric cyano and a 1,2,3‐triazole nucleobase as potential antiviral
agents. Sierocki P. ; Gaillard, K. ; Arellano Reyes, R.A. ; Donnart, C. ; Lambert, E. ; Grosse, S. ; Arzel, L. ; Tessier, A. ;
Guillemont, J. ; Mathé‐Allainmat, M. ; Lebreton, J. Org. Biomol. Chem. 2022, 20, 2715‐2728. DOI : 10.1039/D1OB02451E
2 Autophagy and evasion of immune system by SARS‐CoV‐2. Structural features of the Non‐structural protein 6 from Wild
Type and Omicron viral strains interacting with a model lipid bilayer. Bignon, E. ; Marazzi, M. ; Grandemange, S. ; Monari, A.
BioRxiv 2022, DOI : 10.1101/2022.01.05.475107.
The PhD student will be under the responsibility of the Director of CEISAM and will work in collaboration with a University Professor (Prof. Jacques Lebreton) and a CNRS Researcher (Arnaud Tessier).
The PhD student will be integrated into the Symbiose team which deals with the synthesis of molecules of biological interest and the development of synthetic methodology. The PhD student will interact in a strong way with the employees working in the
laboratory, whether in the field of analysis or synthesis.
Constraints and risks
The candidate must hold a master's degree in molecular chemistry. Experience and interest in the chemistry-biology interface are required.
General, theoretical or disciplinary knowledge:
- Good knowledge of the main techniques of synthesis, purification and characterization of molecules.
- Fluency in English desired
- Know how to lead a project
- Know how to communicate and promote the work (presentation of poster, participation in congress, ...)
- Know how to implement protocols in organic synthesis (batch synthesis of a few mg to a few grams).
- Know how to use specific synthesis and purification devices (Ozone generator, Rotary oven, Puriflash, etc.)
- Know how to use common analytical devices and interpret analytical data (NMR, IR, MS, UV, etc.)
- Use of software in the fields of bibliography and analytical data processing (NMR, IR, SM, UV, etc.)
- Know how to interpret analytical data
- In-depth knowledge of health and safety rules as well as good laboratory practices.).
- Have qualities of work organization and responsiveness
- Have good interpersonal skills and interact with colleagues
- Be rigorous and methodical
- Ability to work in a team.
- Take initiatives while being accountable
- Ability to meet deadlines and deadlines
- Compliance with confidentiality obligations
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