COVID-19 infection in human cellular models: search for effective therapeutic strategies

Abstract

The Center of Excellence in New Target Discovery (CENTD) is the result of a partnership between the Butantan Institute and the São Paulo Research Foundation (FAPESP) and the Pharmaceutical GlaxoSmithKline (GSK). It aims to identify and validate new molecular targets and signaling pathways involved in inflammatory diseases. For the identification of these molecular targets, animal venoms, toxins, molecules isolated from different animal secretions, as well as their peptide derivatives are being used. The discovery of new targets and their validation may allow the development of new drugs. There is a new public health crisis that threatens the world with the emergence and spread of the new coronavirus 2019 (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease is mild in most people, but in the elderly and individuals with comorbidities, it can progress to pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. The lethality rate currently stands at 4%. Treatment is essentially supportive. The role of antiviral agents has not yet been established. Faced with the pandemic situation of the disease caused by SARS-CoV-2 and the competence developed by CENTD, throughout these years of its activity, our team in association with new collaborators from the Viral Biotechnology, Virology and Biopharmaceutical Laboratories of the Butantan Institute, Virology Laboratory of the Institute of Biomedical Sciences of the University of São Paulo and the Institutes of Biotechnology / Molecular Biology and Experimental Medicine at CONICET, Argentina, intends to make efforts to contribute to a better understanding of this disease. Thus, this project aims to evaluate the inflammatory events triggered by SARS-CoV-2, in different cell models (pulmonary epithelial cells, endothelial cells and in human monocytes / macrophages), and their regulation by the use of molecules derived from animal secretions, potentially antiviral drugs, human monoclonal antibodies, as well as mesenchymal stem cells. Such an analysis will be carried out using a multidisciplinary approach that includes classic virology methods, cellular and molecular biology techniques and analyzes of immunological and pharmacological aspects. To identify the possible signaling pathways involved, additional approaches will be applied, including the use of specific pathway agonists or inhibitors.