Inhibition of coronaviruses infections using innovative nanostructures – NanoMERS

The nanoMERS project is planned for 42 months and the work is structured into four work packages. The activities within the WPs will be carried out in close synergy with each other.
WP 1: Coordination, Management and Dissemination
WP 2 : Synthesis/Characterization of nanomaterials with anti-MERS activity
WP 3 : Identification of most efficient anti-MERS-CoV structures: in vitro tests
WP4: Nanoparticle encapsulation in PLGA nanoparticles; lung biodistribution, in vivo lung toxicity

We showed lately the antiviral activity of seven different carbon quantum dots (CQDs) for the treatment of human coronavirus HCoV-229E infections, a very timy topic under the COVID-19 panepedemi. The first generation of antiviral CQDs was derived by hydrothermal carbonization from ethylenediamine/citric acid as carbon precursors and post-modified with boronic acid ligands. These nanostructures showed a concentration dependent virus inactivation with an estimated EC50 of 52±8 µg mL-1. CQDs derived from 4-aminophenylboronic acid without any further modification resulted in the second-generation of anti-HCoV nanomaterials with an EC50 lowered to 5.2±0.7 µg mL-1. The underlying mechanism of action of these CQDs revealed to be inhibition of HCoV-229E entry that could be due to interaction of the functional groups of the CQDs with HCoV-229E entry receptors; surprisingly, an equally large inhibition activity was observed at the viral replication step.

Identification of anti-MERS-CoV activity of peptides and/or monoclonal nanostructures

Integration of MERS specific ligands to the nanostructures

Pulmonary delivery of the best antiviral nanostructure

Analysis of inflammation markers to understand better eventual lung toxicity of nanoparticles

Testing of most promising anti-MERS structures in MERS-CoV infected 3D reconstructed human respiratory epitheliums.

A. Loczechin, K. Séron, A. Barras, S. Belouzard, Y.-T. Chen, N. Metzler-Nolte, R. Boukherroub, J. Dubuisson, S. Szunerits
ACS Applied Materials and Interfacs 2019, 11, 46, 42964-42974
Functional Carbon quantum dot as medical countermeasures to humancorona virus (HCoV)

The eradication of viral infections is an ongoing challenge in the medical field, not only due to the problem of spreading but also to virus ability to evolve by genetic mutations. In contrast to bacterial infections which are mostly treated using antibiotics, antiviral treatment development is difficult and immunization against viral infections is not always possible. These considerations apply also to respiratory diseases caused by human coronavirus (HCoV) infections. Initially, Middle-East Respiratory Syndrome coronavirus (MERS-CoV) infections occurred sporadically; however, horizontal infection among human patients observed particularly in hospital and nosocomial settings has raised concerns about the pandemic potential of MERS-CoV.

The main goal of the NanoMERS project is the identification of specific and efficient nanomaterials derived anti-MERS-CoV agents effectively inhibiting viral entry and their in vitro and in vivo testing. This multi-disciplinary project involves 3 teams (IEMN-University Lille, Institut Galien Paris-Sud; Center for Infection & Immunity of Lille) that are highly complementary due to the technical pre-existing know-how of each partner. The focus will be on the use of carbon based nanostructures, notably modified C-dots and graphene-dots and nanoparticle formulations of poly(D, L-lactide-co-glycolide) (PLGA). Identification of most promising anti-MERS-CoV nanostructures using in vitro tests, determination of the pharmacokinetic of the best nanostructures, the possibility of pulmonary delivery using nebulization of mice as well as testing of most promising anti-MERS structures in MERS-CoV infected 3D reconstituted human respiratory epitheliums are the main objectives.