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.
