Investigation of antimalarial activity and molecular targets of natural compounds identified by chemoinformatics against Plasmodium vivax

• Grant number: 19/02171-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2019
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Fabio Trindade Maranhão Costa
• Grantee: Letícia Tiburcio Ferreira
• 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
• Associated scholarship(s): 21/13809-9 - Investigation of antimalarial activity and molecular targets of natural compounds identified by chemoinformatics and genetic analysis of Plasmodium falciparum parasites, BE.EP.DR

Abstract

Malaria remains a public health issue, with about 219 million cases registered globally in 2017. Alongside with Venezuela, Brazil still accounts for most of the disease cases in the Americas. Among the species able to infect humans, P. Vivax is responsible for almost all cases in Brazil and presents more and more severe cases, breaking the paradigm of Vivax Malaria as a benign infection. Parasite strains resistant to chloroquine already circulate in endemic areas and therefore there is a need to search for new antimalarial drugs, especially against Vivax Malaria. Regions such as the Amazon - endemic to Malaria- are rich in biodiversity and therefore harbor potential bioactive compounds. Natural products are part of the development process of one third of the drugs introduced in the market in the last thirty years. Hence, as an abundant and diverse source of chemical structures with biological activity, natural products share the pharmacophoric characteristics and are a rich source of scaffolds for medicinal chemistry. Facing drug discovery, the computer-aided drug design optimizes the identification of drug candidate bioactive molecules, including potential antimalarials, reducing the burden of phenotypic screening trials and increasing the chances of success. Thus, combining chemoinformatics and experimental strategies, this project aims to perform ligand-based in silico screenings for the identification and later experimental validation of natural and synthetic compounds with potential antimalarial activity, seeking to identify the molecular targets for the more promising compounds. Thus, we sought to cooperate with knowledge availability and new treatments for the control of Vivax Malaria. (AU)

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)

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)

VOLPE-ZANUTTO, FABIANA; FERREIRA, LETICIA TIBURCIO; PERMANA, ANDI DIAN; KIRKBY, MELISSA; PAREDES, ALEJANDRO J.; VORA, LALITKUMAR K.; BONFANTI, AMANDA P.; CHARLIE-SILVA, IVES; RAPOSO, CATARINA; FIGUEIREDO, MARIANA C.; et al. Artemether and lumefantrine dissolving microneedle patches with improved pharmacokinetic performance and antimalarial efficacy in mice infected with Plasmodium yoelii. JOURNAL OF CONTROLLED RELEASE, v. 333, p. 298-315, MAY 10 2021. (19/02171-3, 16/18384-8, 14/16008-3, 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)