High-throughput virtual screening in the design of main protease inhibitors of the novel coronavirus

• Grant number: 23/18211-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Cristiane Rodrigues Guzzo Carvalho
• Grantee: Anacleto Silva de Souza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 25/05583-1 - Multiscale coarse-grained molecular dynamics simulations of Wuhan, Delta, and Omicron strains of SARS-CoV-2 and novel HKU5-CoV Lineage 2, BE.EP.PD

Abstract

The emergence of new variants of concern (VOCs) of the novel coronavirus has generated uncertainties about the outcome of the greatest pandemic of the 21st century. These variants are capable of evading the immune system and are more transmissible. Despite progress in vaccination in Brazil, immunization alone is not sufficient to contain the virus's spread. Therefore, it becomes essential to explore effective alternatives in the treatment of the disease, especially given the high cost of drugs approved by ANVISA. In this context, we propose the initial construction of an extensive database, comprising over 1500 bioactive molecules in the main enzyme of SARS-CoV-2. In subsequent phases, advanced molecular filtering strategies will be applied, involving decision tree models, Bayesian networks, deep learning, and other machine learning approaches. These techniques will be combined with molecular docking, and molecular dynamics, enabling virtual screening of 230 million chemical structures in the ZINC20 database. The goal is to identify new bioactive frameworks in the virus's enzyme. Upon completion of this study, we aim to discover new bioactive molecules, which will undergo in vitro testing on 3CLpro and cells infected by SARS-CoV-2. This research aims to establish a solid foundation for innovation in the development of new generations of anti-SARS-CoV-2 drugs, characterized by effectiveness and, crucially, affordability.

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)

VISNARDI, ALINE BIAZOLA; RIBEIRO, RODOLFO ALVARENGA; DE SOUZA, ANACLETO SILVA; VINCES, TANIA GERALDINE CHURASACARI; LLONTOP, EDGAR E.; FERRARI, ANIELLE SALVIANO DE ALMEIDA; HENRIQUE, PEDRO ANTONIO FRANCA; VALDIVIESO, DANIELA; SANCHEZ-LIMACHE, DANIEL ENRIQUE; SILVA, GABRIELA ROBERTO; et al. Insertion of a Divergent GAF-like Domain Defines a Novel Family of YcgR Homologues That Bind c-di-GMP in Leptospirales. ACS OMEGA, v. 10, n. 4, p. 19-pg., 2025-01-21. (20/04680-0, 19/00195-2, 21/05262-0, 21/00070-5, 21/10577-0, 17/17303-7, 23/10432-7, 17/06394-1, 16/09047-8, 23/18211-0, 22/08730-7)

DE ALMEIDA, MICHELLE TEIXEIRA; MERIGHI, DAVI GABRIEL SALUSTIANO; VISNARDI, ALINE BIAZOLA; GONCALVES, CAUE AUGUSTO BONETO; AMORIM, VITOR MARTINS DE FREITAS; FERRARI, ANIELLE SALVIANO DE ALMEIDA; DE SOUZA, ANACLETO SILVA; GUZZO, CRISTIANE RODRIGUES. Latin America's Dengue Outbreak Poses a Global Health Threat. Viruses-Basel, v. 17, n. 1, p. 32-pg., 2025-01-01. (23/13894-1, 21/05262-0, 21/10577-0, 23/18211-0, 22/08730-7, 23/07366-2)