Titolo della tesi: Structural bioinformatics analysis of the SARS-COV-2 proteome evolution to characterize the emerging variants of the virus and to suggest possible therapeutic strategies
SARS-CoV-2 is a new coronavirus responsible for the global COVID-19 pandemic, detected in China in December 2019 and that has spread rapidly across the world. Our unit, with its specific expertise in structural bioinformatics and molecular modelling, has been involved in collaboration with epidemiology and molecular genetics groups to study SARS-CoV-2 proteome and to suggest possible molecular strategies able to inhibit virus infection. All coronaviruses, including SARS-CoV-2, evolves and adapts to the host through accumulation of mutations generated by characteristics of the virus RNA-polymerase. This work can be divided into two parts: the first part is focused onto the predictions of the potential effects of the mutations on the functions of the SARS-CoV-2 Spike glycoprotein, whereas the second part is focused at suggesting possible therapeutic strategies. In particular, I performed docking analyses to study the possible mode ad sites of interaction of inorganic polyphosphates with ACE2 and RdRp because the molecular genetics group with whom we collaborate suggested that polyphosphates can enhance ACE2 proteasomal degradation and impair synthesis of viral RNA. In addition, I developed a pipeline to predict the most frequent sites of interaction between Spike glycoprotein and neutralizing monoclonal antibodies in order to propose therapeutic alternatives more specific and selective.