Ricerc@Sapienza

Coronaviruses (CoVs) are the etiological agents of either common colds and severe diseases such as the 2002 Severe Acute Respiratory Syndrome (SARS-CoV-1) and the 2012 Middle East Respiratory Syndrome (MERS-CoV). In 2019 the viral strain SARS-CoV-2 previously not detected in humans was identified in China as responsible for the current global outbreak.
All these epidemics are commonly associated with the elevated genetic mutation rates, which translate into a high probability to infect hosts, including humans (i.e., zoonosis). No specific drugs are yet available to effectively treat COrona VIrus Diseases (COVID-19) as many associated morbidities and deaths are constantly recorded.
Currently, media brainstorm on the use of vaccines shadows and drains out important resources, which are vital to foster the progress (although discrete) in developing adequate drugs to tackle SARS-CoV-2 spreading and its associated diseases. At present, the only effective measures still are precautional and all aimed to avoid any viral transmission among individuals. However, the containment measures adopted have a dramatic impact on the economy and social life. Therefore, the identification of drugs that can impair viral replication and effective in the ongoing pandemic are in high demand.
This project aims to identify new and effective inhibitors of the main protease (Mpro) and papain-like protease (PLP) of SARS-CoV-2, as well as SARS-CoV-1 and MERS, by mean of a skillful and complementary combination of computational and experimental approaches. Specifically, the target-based in silico screening will use multiple Mpro and PLP crystallographic structures available as templates. Inhibition of Mpros and PLPs by most promising virtual hits will be assessed using lab bench biochemical assays and then further investigated for their antiviral activity through in vitro cellular and in vivo experiments.