• IEMN Project Sponsor: Henri Happy
• Coordinator: IEMN
  
• Partners: IBMP Institut de biologie moléculaire des plantes (UPR 2357)
  ITODYS Interfaces, Traitements, Organisation et Dynamique des Systèmes
  IEMN UMR 8520 – IEMN – Institut d’Electronique, de Microélectronique et de Nanotechnologie
  University of Regensburg University of Regensburg
  UCLouvain Université catholique de Louvain
  Centre for Adv. Materials Application Centre for Advanced Materials Application

Abstract:

Viruses are small intracellular parasites, which by definition contain either a RNA or DNA genome surrounded by a protective structure consisting of proteins and additional lipids when enveloped. These parasites are very diverse in shape, size, composition and hosts covering the entire living world. Due to this diversity, the development of a simple and “general approach” for virus detection remains thus highly challenging. While polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) have become the gold standards for the identification and quantification of viruses, these methods are targeted and require prior knowledge of the specific virus to be detected similarly to antigen-based methods such as ELISA. PCR for the detection can also challenging due to the propensity of viruses to mutate at high frequency.

Long viral double-stranded RNA (dsRNA) is considered a universal biomarker for the presence of virus and a unique hallmark of many viral infections. dsRNA is produced either by RNA viruses during replication or by DNA viruses upon convergent transcription. Thus, unlike single-stranded RNA and short RNA duplexes like siRNA, the presence of dsRNA >40 base pairs in the cytoplasm of cells is generally a sign of viral infection and triggers innate immune responses. Detection of these long dsRNA is currently based on time-consuming and costly immunofluorescence using dsRNA specific antibodies.

Paradoxically, dsRNA-centred viral surveillance strategies have not yet inspired widespread research initiatives. We believe this is partially due to the lack of deeper knowledge about the dynamic viral RNA-protein interactions, essential to understanding their evolution and adaptation to distinct hosts and environments, and critical for developing virus surveillance sensors.

G-Virals aims to overcome these challenges and knowledge gaps by focusing on the extraordinary dsRNA binding properties of proteins such as B2. Integration of dsRNA binding proteins into a panel of differently constructed graphene-based field effect transistors (gFETs) and connection to lab-on-chip based pre-analytical steps will allow quantification of viral dsRNA in a point-of-need sensing platform. Next to studying the key operational characteristics of this novel virus warning systems, flash Joule heating of biomedical wait will prepare “flash” graphene inks for gFET designs in parallel. G-Virals proposes the first generic approach for viral surveillance via the development of dsRNA-to-graphene. Implementation of precision qRT-PCR and third-generation sequencing (e.g., nanopore technology) in case of a positive sensor responses, will further result in virus identification. G-Virals will strongly impact responses to future and emerging viral diseases via the proposed systems of virus surveillance.