Interference with the Assembly of SARS-CoV-2 virions Targeting E Protein by rational drug design

• Grant number: 22/01812-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Carsten Wrenger
• Grantee: Lizdany Florez Alvarez
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/26722-8 - Drug discovery against human infectious diseases, AP.TEM
• Associated scholarship(s): 24/03520-0 - Interference with the Assembly of SARS-CoV-2 virions Targeting E Protein by rational drug design, BE.EP.DR

Abstract

The aim of this research project is to evaluate the effect of molecules selected by rational drug design to interfere with SARS-CoV-2 virion production in vitro by targeting the E protein of the virus.The capacity of CoV E protein to form homo-oligomers targeted to the Golgi membrane has been widely described. Recently, this structure forming an ion channel has been attributed to neutralization of the Golgi pH avoiding the early proteolytic processing of CoV S (spike), preserving its structure allowing an infective progeny. To Interfere with the function of the CoV E protein will affect virus assembly and release and pave the way for identifying novel antiviral therapeutics.In this sense we intend to evaluate the effect of specific compounds directed against the ion channel function of the CoV E protein trough proliferation assays located in the departmental BSL3 cell culture facility and verify the mechanism of action by visualizing the Golgi neutralization using fluorescence microscopy on Golgi membrane anchored pH sensitive deGFP4 expressing host cell lines.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FLOREZ-ALVAREZ, LIZDANY; DE SOUZA, EDMARCIA ELISA; BOTOSSO, VIVIANE FONGARO; LEAL DE OLIVEIRA, DANIELLE BRUNA; HO, PAULO LEE; TABORDA, CARLOS PELLESCHI; PALMISANO, GIUSEPPE; CAPURRO, MARGARETH LARA; REBELLO PINHO, JOAO RENATO; FERREIRA, HELENA LAGE; et al. Hemorrhagic fever viruses: Pathogenesis, therapeutics, and emerging and re-emerging potential. FRONTIERS IN MICROBIOLOGY, v. 13, p. 16-pg., 2022-10-25. (16/20045-7, 19/12303-4, 18/18257-1, 20/04923-0, 17/03966-4, 17/27131-9, 22/01812-8, 18/15549-1, 15/26722-8, 20/12277-0, 20/06409-1, 16/08730-6)