Antiviral molecules against Coronavirus employing PROTACs Technology

Anno
2021
Proponente Domenico Raimondo - Professore Associato
Sottosettore ERC del proponente del progetto
LS2_12
Componenti gruppo di ricerca
Componente Categoria
Alessia Mariano Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca
Abstract

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic represents a tragic phenomenon reminding us that new viral pandemics can occur at any time.
Vaccination is the first choice to contain a pandemic, but there are issues related to massive active immunization campaigns, as individual resistance. Moreover, there are categories who cannot be vaccinated or do not respond efficiently to vaccination, e.g., immunosuppressed patients and transplant recipients. Vaccines are also usually expensive and a long time is needed to reach the herd immunity. Finally, their storage and distribution are not always straightforward. Conversely, broad-spectrum antiviral drugs would have the advantages to be outbreak-ready and the possibility to be administered also to people for which vaccination is not recommended.
In recent years, PROteolytic TArgeting Chimeras (PROTACs) technology has emerged as one of the most intriguing approaches in drug design. PROTACs are bifunctional molecules able to induce target protein degradation rather than inhibition and represent a new frontier of pharmaceutical research, with two PROTACs already in phase I clinical trials.
This proposal aims to rationally search new potential molecules based on PROTAC technology against one target of SARS-CoV-2.
Despite the great interest, the use of PROTAC technology is still marginal in the field of antivirals. We will develop small molecule PROTACs targeting the main protease (Mpro). Both the catalytic site and the dimerization surface will be explored as druggable targets, since Mpro is active in its dimeric form. The collaborative work of different research units will guarantee a multidisciplinary approach to develop a starting platform for the development of anti-CoVs agents.

ERC
LS2_12, LS7_4, LS9_1
Keywords:
MEDICINA MOLECOLARE, BIOINFORMATICA, SCOPERTA E DESIGN DI FARMACI, BIOLOGIA COMPUTAZIONALE, CHIMICA COMPUTAZIONALE

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