Analisi della mutabilità del proteoma di SarS-CoV-2

Anno
2020
Proponente Stefano Pascarella - Professore Ordinario
Sottosettore ERC del proponente del progetto
LS2_12
Componenti gruppo di ricerca
Componente Categoria
Martina Bianchi Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca
Abstract

The etiological agent of COVID-19 is a Coronavirus which was named Sars-CoV-2 (Severe acute respiratory syndrome CoronaVirus 2). The genome of the virus possesses a single stranded positive RNA and is about 30kb long. The genome codes for two large overlapping polyproteins that are processed by intracellular proteolysis to produce non-structural proteins involved in virus replication and assembly. The CoV evolves and adapts to the host through accumulation of mutations generated by several mechanisms also linked to the virus RNA-dependent-RNA-polymerase (RdRp) activity. Currently, many initiatives are ongoing worldwide to develop an effective vaccine or to find or to reposition drug candidates able to prevent virus infection and/or replication.
In this context, it is important to understand the dynamics of evolution of the virus and to study how its proteome changes. Indeed, modification of specific virus proteins considered promising targets for therapy may jeopardize most of the efforts; moreover, even single mutations in specific proteins can change pathogenicity or contagiousness of the virus.
In this project, we propose a systematic screening of the Sars-CoV-2 genome isolates to scrutinize the position, type and the prevalence of specific mutations in each of the protein expressed by the virus. This activity will require the development of a software workflow able to carry out all the necessary steps on a large amount of genomic data.
Sars-CoV-2 genome sequences will be taken from GISAID repository. Tools from BLAST and EMBOSS suites will be utilized to analyse and translate nucleotide sequences. Sequence redundancy will be removed by clustering techniques. Multiple sequence alignments between each reference protein and the cognate variants will be analysed by R scripts able to collect various statistics. Whenever possible, it will be attempted to correlate pervasiveness of protein variants with structural and functional properties.

ERC
LS2_12, LS6_5, LS2_13
Keywords:
BIOINFORMATICA, VIROLOGIA, GENOMICA, BIOCHIMICA

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