Drug discovery against human infectious diseases

• Grant number: 20/12277-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2020
• End date: November 30, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carsten Wrenger
• Grantee: Edmarcia Elisa de Souza
• 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

Abstract

Infectious diseases are a threat to mankind and currently the causative pathogens are spreading geographically due to globalisation and developing drug resistance. Current resistance to chemotherapeutics is occurring to almost all pathogens and therefore new drug targets and/or novel modi of drug target efficacy is urgently needed. In this grant application the focus will be drawn on suicide drug discovery by exploiting the vitamin B1/B6 biosynthetic pathways of the human pathogens Plasmodium falciparum, the parasite responsible for predominate cases of severe malaria, and the multi-resistant bacteria Staphylococcus aureus MRSA. Compounds will be identified and designed for incorporation into pathogens' metabolism after crystal structure evaluation of the respective vitamin B1/B6 biosynthetic enzymes. Thereby the new compounds are intended to poison the respective vitamin dependent enzyme. Counter selection will be performed against human cells as well as transgenically modified human cells which are expressing nuclear receptors for xenobiotic sensing as report gene chimeras. (AU)

Scientific publications

(6)

(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)

BOTOSSO, VIVIANE FONGARO; DURIGON, EDISON LUIZ; DE SOUZA, EDMARCIA ELISA. Emerging human viruses with pandemic potential: Diagnostics, pathogenesis, and therapeutics. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 13, p. 2-pg., 2023-03-23. (20/12277-0, 21/11946-9, 15/26722-8)

MACEDO-DA-SILVA, JANAINA; ROSA-FERNANDES, LIVIA; GOMES, VINICIUS DE MORAIS; SANTIAGO, VERONICA FEIJOLI; SANTOS, DEIVID MARTINS; MOLNAR, CATARINA MARIA STANISCHESK; BARBOZA, BRUNO RAFAEL; DE SOUZA, EDMARCIA ELISA; MARQUES, RODOLFO FERREIRA; BOSCARDIN, SILVIA BEATRIZ; et al. Protein Arginylation Is Regulated during SARS-CoV-2 Infection. Viruses-Basel, v. 15, n. 2, p. 25-pg., 2023-02-01. (18/15549-1, 18/18257-1, 20/06409-1, 22/09915-0, 20/02988-7, 21/00140-3, 20/12277-0, 21/14179-9, 15/26722-8)

SRINIVASAN, VASUNDARA; BROGNARO, HEVILA; PRABHU, PRINCE R.; DE SOUZA, EDMARCIA ELISA; GUENTHER, SEBASTIAN; REINKE, PATRICK Y. A.; LANE, THOMAS J.; GINN, HELEN; HAN, HUIJONG; EWERT, WIEBKE; et al. Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease. COMMUNICATIONS BIOLOGY, v. 5, n. 1, p. 12-pg., 2022-08-11. (15/26722-8, 19/00899-0, 20/12277-0)

SUMAM DE OLIVEIRA, DAFFINY; KRONENBERGER, THALES; PALMISANO, GIUSEPPE; WRENGER, CARSTEN; DE SOUZA, EDMARCIA ELISA. Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, JUN 10 2021. (18/10150-3, 20/04923-0, 19/26771-0, 20/12277-0, 17/03966-4, 18/18257-1, 18/15549-1, 15/26722-8)

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)

MIRANDA, RENATA RANK; FERREIRA, NATALIA NORONHA; DE SOUZA, EDMARCIA ELISA; PINCELA LINS, PAULA MARIA; BARBOZA FERREIRA, LEONARDO MIZIARA; KRUGER, ARNE; DE OLIVEIRA CARDOSO, VALERIA MARIA; DURIGON, EDISON LUIZ; WRENGER, CARSTEN; ZUCOLOTTO, VALTENCIR. Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System. ACS APPLIED BIO MATERIALS, v. N/A, p. 13-pg., 2022-06-22. (19/25645-0, 20/12277-0, 18/08820-0, 15/26722-8)