COVID-19: Approaches for antiviral drug development

Anno
2020
Proponente Guido Antonelli - Professore Ordinario
Sottosettore ERC del proponente del progetto
LS6_7
Componenti gruppo di ricerca
Componente Categoria
Gianluca Vrenna Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group
Alessandra Carattoli Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Paolo Guglielmi Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Giammarco Raponi Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Componente Qualifica Struttura Categoria
Maria Rosaria Capobianchi Head of the Virology Laboratory INMI L. Spallanzani Rome Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships
Abstract

The proposal ¿Rational Quest toolkit for therapeUtics and risk assEssmEnt in the nCoV coNtext¿ (acronym: QUEEN) has been submitted in response to the H2020 Call: SC1-PHE-CORONAVIRUS-2020, with the participation of the Sapienza Unit leaded by prof. Guido Antonelli. The main aim of the proposal was to develop a powerful tool (the QUEEN Hit Finder tool) to quickly screen among thousands of available drugs contained in online databases through computational molecular modeling. This extensive virtual screening campaign would be supported by a massive set of wet-lab experiments (from proteins binding affinity assays to in vivo experiments). In the QUEEN project, the group of Sapienza University proposed to investigate on sensitive cell culture models, the efficacy of compounds selected by the partner¿s computational tool and perform transcriptome analysis of infected cells in the presence of the candidate drug(s).
The identification of natural compounds able to act as antiviral drugs that can inhibit SARS-CoV-2 infection and/or replication would represent a powerful step to enhance the response to a possible second wave of the pandemic virus. We will utilize experimental in vitro CoV infections, first with the low-pathogenic CoV OC43, and NL63, and then with SARS-CoV-2, to test for inhibition of viral infection, decrease in replication and activation of the innate immune response using molecular and cellular biology techniques. In particular, we here propose: 1) to screen in silico the in house library of the Department of Chemistry and Technology of Drugs (plant-derived natural compounds and antimicrobial peptides) for interactions with the processes of SARS-CoV-2 entry and replication; 2) infecting permissive cells with the CoVs OC43, NL63, and SARS-CoV-2, in the presence of the selected compounds in order to evaluate their antiviral activity; 3) studying the impact of the selected compounds on innate immunity.

ERC
LS7_4, LS7_10, LS7_3
Keywords:
MALATTIE INFETTIVE, SCOPERTA DI FARMACI, SCOPERTA E DESIGN DI FARMACI, IMMUNITA¿ INNATA, VIROLOGIA

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