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Interaction studies between cellular proteins and viral proteins of the new coronavirus 2019 (SARS-CoV-2)

Grant number: 20/05346-6
Support type:Regular Research Grants
Duration: July 01, 2020 - June 30, 2022
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Fernando Moreira Simabuco
Grantee:Fernando Moreira Simabuco
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Assoc. researchers:Adriana Franco Paes Leme ; Armando Morais Ventura ; Augusto Ducati Luchessi ; Carlos Frederico Martins Menck ; Isadora Carolina Betim Pavan
Associated research grant:18/14818-9 - Study of molecular targets important for the control of cancer metabolism: the mTOR/S6K pathway as a central role, AP.JP2

Abstract

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), like SARS-CoV from 2003 and MERS-CoV from 2012, is part of the Betacoronavirus genus of the Nidovirales order and is currently the virus that causes the pandemic called COVID- 19 (Coronavirus disease 2019). SARS-CoV-2 causes an acute respiratory disease or SARS, characterized by fever, cough, fatigue and severe cases of pneumonia, having affected more than 1.9 million people worldwide so far. Three of the structural proteins of the virus, the E, M, and N proteins, are responsible for assembling the viral particle, among other processes. N protein has a high affinity for the viral RNA, forming the viral nucleocapsid. The membrane proteins E and M are responsible for virion morphology and for interactions with S protein, which recognizes the cell receptor, and with the viral nucleocapsid. The replication process of the coronaviruses is highly regulated, involving different actions between the structural and the nonstructural proteins of the virus. However, few are known regarding the cellular proteins involved in the assembly of viral particles of coronaviruses. This project aims to identify the interactome of SARS-CoV-2 E, M and N proteins in human cells, understanding their molecular interactions with cellular proteins and the cellular pathways that benefit the virus to carry out its replication cycle. Therefore, we will optimize the viral genes that encode E, M, and N for expression in human cells, followed by immunoprecipitation and mass spectrometry characterization of the interacting cellular proteins. Once validated, these interactions will be challenged with pharmacological interventions in vitro, to verify their potential to block or interfere with viral replication. These compounds will be finally tested in an in vitro model of human cells infected with SARS-CoV-2, analyzing viral load, cytopathic effect and molecular changes in the cells. The present research project intends, therefore, to contribute to a better understanding of the molecular and cellular mechanisms associated with the replication of SARS-CoV-2 in human cells and to a rationalization of possible future therapies against COVID-19. (AU)