Kinase prioritization and discovery of compounds with anti-malarial activity against different stages of Plasmodium vivax using chemogenomics, bioinformatics, cheminformatics, and experimental evaluation tools

• Grant number: 19/21854-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2020
• End date: May 31, 2022
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Fabio Trindade Maranhão Costa
• Grantee: Joyce Villa Verde Bastos Borba
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax, AP.TEM

Abstract

Malaria is one of the main diseases in tropical and subtropical countries in the world, caused by protozoa from the genus Plasmodium. Nowadays, the main strategy in the control of Malaria is based on the treatment. The always-recurrent resistance to the antimalarial drugs is a big barrier to the battle against Malaria, leading to new outbreaks of the disease. Among the potential new therapeutic targets against Malaria, the protein kinases stand out for their capabilities to interfere in other protein's activities through phosphorylation and for their involvement in almost all cellular processes. The kinome study is very important for the understanding of parasite physiology and gives information about how to interrupt adaptive mechanisms of these organisms. Computer-Aided Drug Design (CADD) is considered a great strategy to increase the success rate in the discovery of active compounds with a smaller cost. In this sense, the goal of this work plan is the identification of compounds that target kinases with antiplasmodial activity in P. vivax isolates through chemogenomics, bioinformatics, cheminformatics, and experimental assays strategies. To achieve this goal, we will characterize and update the kinome of different Plasmodium species, prioritize kinases as therapeutic targets and repurpose drugs that might target these kinases. We will also develop an integrative in silico platform to the discovery of new multistage antimalarial drugs. (AU)

Scientific publications

(5)

(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)

VERDE BASTOS BORBA, JOYCE VILLA; SILVA, ARTHUR CARVALHO; NASCIMENTO LIMA, MARILIA NUNES; MENDONCA, SABRINA SILVA; FURNHAM, NICHOLAS; MARANHAO COSTA, FABIO TRINDADE; ANDRADE, CAROLINA HORTA; DONEV, R. Chemogenomics and bioinformatics approaches for prioritizing kinases as drug targets for neglected tropical diseases. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY, VOL 124: PROTEIN KINASES IN DRUG DISCOVERY, v. 124, p. 37-pg., 2021-01-01. (17/18611-7, 19/21854-4)

LIMA, MARILIA N. N.; BORBA, JOYCE V. B.; CASSIANO, GUSTAVO C.; MOTTIN, MELINA; MENDONCA, SABRINA S.; SILVA, ARTHUR C.; TOMAZ, KAIRA C. P.; CALIT, JULIANA; BARGIERI, DANIEL Y.; COSTA, FABIO T. M.; et al. Artificial Intelligence Applied to the Rapid Identification of New Antimalarial Candidates with Dual-Stage Activity. CHEMMEDCHEM, v. 16, n. 7, p. 1093-1103, APR 8 2021. (15/20774-6, 13/13119-6, 17/18611-7, 18/24878-9, 18/07007-4, 19/21854-4)

VERDE BASTOS BORBA, JOYCE VILLA; SILVA, ARTHUR DE CARVALHO E.; DO NASCIMENTO, MARILIA NUNES; FERREIRA, LETICIA TIBURCIO; RIMOLDI, ALINE; STARLING, LUISA; PEREIRA RAMOS, PABLO IVAN; MARANHAO COSTA, FABIO TRINDADE; ANDRADE, CAROLINA HORTA. Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malaria. COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, v. 20, p. 10-pg., 2022-07-15. (19/21854-4, 20/02158-4, 19/02171-3)

BORBA, JOYCE V. B.; DE AZEVEDO, BEATRIZ ROSA; FERREIRA, LARISSA A.; RIMOLDI, ALINE; ALVAREZ, LUIS C. SALAZAR; CALIT, JULIANA; BARGIERI, DANIEL Y.; COSTA, FABIO T. M.; ANDRADE, CAROLINA HORTA. Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity. ACS OMEGA, v. 8, n. 37, p. 7-pg., 2023-09-05. (18/24878-9, 19/21854-4, 21/06769-0, 17/18611-7)

FERREIRA, LETICIA TIBURCIO; BORBA, JOYCE V. B.; MOREIRA-FILHO, JOSE TEOFILO; RIMOLDI, ALINE; ANDRADE, CAROLINA HORTA; COSTA, FABIO TRINDADE MARANHAO. QSAR-Based Virtual Screening of Natural Products Database for Identification of Potent Antimalarial Hits. BIOMOLECULES, v. 11, n. 3, MAR 2021. (19/21854-4, 19/02171-3, 20/02158-4, 17/18611-7)