Exploring the non-structural protease NSP2 from Chikungunya and Mayaro viruses: structures and inhibition

• Grant number: 18/07572-3
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): October 01, 2018
• Status: Discontinued
• Field of knowledge: Biological Sciences - Biophysics
• Principal Investigator: Raghuvir Krishnaswamy Arni
• Grantee: Raphael Josef Eberle
• Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated scholarship(s): 19/05614-3 - Identification of bioactive molecules which inhibit both Chikungunya and Mayaro virus activities, BE.EP.PD

Abstract

Infection by the Chikungunya virus results in considerable social and economic trauma and requires urgent attention. The lack of efficacious treatments is compounded by potential co-infection by Chikungunya and Mayaro which exacerbates and magnifies the problem since both trigger similar reactions and analogous clinical symptoms.The cleavage of the Chikungunya and Mayaro nsP-polyproteins, by the nsP2 cysteine protease is crucial for viral replication; therefore, the identification and characterization of specific inhibitors of the nsP2 cysteine protease is potentially relevant for understanding viral replication and also to serve as a platform for the development of inhibitors that can help develop drugs. A large number of compounds will be screened for binding and inhibition and will be used for structural studies to form complexes with the Chikungunya and Mayaro nsP2 cysteine proteases. These molecules will be subsequently tested in vivo for toxicity and efficacy in collaboration with Prof. Dr. Maurício Lacerda Nogueira (Faculdade de Medicina de São José do Rio Preto (FAMERP), Departamento de Doenças Infecciosas e Parasitárias, Laboratório de Pesquisas Em Virologia).Our earlier research with Zika virus(Led by Dr. M.A. Coronado) has resulted in the expression and purification of the NS2B-NS3 protease and the identification of potent inhibitors that were subsequently characterized by biochemical and biophysical techniques in collaboration with Prof. D. Willbold (Institute of Complex Systems, Structural Biochemistry, Forschungszentrum Jülich, Germany). These results form the basis of three patent applications, which are being jointly prepared for submission.