: Development of novel broad-spectrum antivirals targeting Enterovirus capsid through medicinal chemistry and structure-guided design

Subject / Objective

Enteroviruses represent a persistent global public health threat, being responsible for a wide spectrum of diseases ranging from mild infections to severe complications such as neurological disorders, myocarditis, and ocular infections. The recent emergence of more virulent variants, notably EV-A71 and EV-D68, associated with severe neurological manifestations, highlights the urgent need for the development of new therapeutic strategies. To date, no specific antiviral targeting enteroviruses is available in clinical practice.

This PhD project aims to develop new antiviral inhibitors targeting the viral capsid protein VP1, a key component involved in viral attachment and entry into host cells. The conserved hydrophobic pockets of this protein represent a strategic opportunity for the design of broad-spectrum antivirals.

Building on previous work conducted in the laboratory, which led to the synthesis and evaluation of more than 400 compounds, this project seeks to optimize initial “hit” molecules displaying micromolar to submicromolar antiviral activity to identify new “lead” candidates [1–9].

The project will rely on a multidisciplinary strategy integrating computer-aided drug design, innovative medicinal chemistry approaches (including radical photocatalysis) [10], in vitro biological evaluation, and pharmacokinetic optimization (ADMET studies and formulation strategies). The goal is to identify broad-spectrum drug candidates targeting enteroviruses and polioviruses, paving the way for future preclinical development.

Candidate’s Profile

We are seeking a highly motivated and talented candidate with a strong interest in antiviral drug discovery and interdisciplinary research at the interface of chemistry and biology.

The ideal candidate should hold (or be close to obtaining) a Master’s degree (MSc) in Medicinal Chemistry, Organic Chemistry, Pharmaceutical Sciences, or a closely related field. A solid background in organic synthesis and medicinal chemistry is essential.

Experience or knowledge in one or more of the following areas will be highly appreciated:

Organic chemirsty

Computer-aided drug design and molecular modelling

Structure-based drug discovery

The candidate should demonstrate:

Strong analytical and problem-solving skills

Ability to work independently as well as in a multidisciplinary team

Interest in translational drug discovery and antiviral research

Good scientific communication skills in English (both written and oral)

Previous research experience through internships or Master’s thesis in medicinal chemistry, antiviral research, or drug design will be considered a strong asset.

The successful candidate will join a multidisciplinary research environment, collaborating with chemists, virologists, and computational scientists, and will contribute to the development of innovative antiviral strategies targeting enteroviruses.