Functional characterization of the replication complex (DNA polymerase) of the Monkeypox virus, aiming the search for antiviral drug candidates

• Grant number: 23/04660-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Glaucius Oliva
• Grantee: Bianca Righetti da Silva
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

In May 2022, the World Health Organization (WHO) was informed of a confirmed case of monkeypox caused by the Monkeypox virus (MPXV) in the United Kingdom, after which there was a rapid spread of the disease in other countries. To date, there are 86,500 confirmed cases around the world, with 10,878 cases in Brazil alone. Viral transmission usually occurs between people or wild animals, either through contact with lesions, body fluids, respiratory droplets or contaminated materials. So far, only one drug, Tecovirimat, has been used on an emergency basis to combat monkeypox. Despite having been approved in 2022 by the European, Brazilian and American health authorities, data from studies in animals and humans are not yet fully available, and therefore, several aspects such as possible complications, dose and long-term sequelae still need to be addressed. be evaluated. The Monkeypox virus, has a genome of 197 kb, belongs to the Orthopoxvirus genus, Poxvirus family and has double-stranded DNA. This virus has two essential polymerases, a DNA polymerase (DNApol) and a DNA-dependent RNA polymerase (DdRp). DNApol is considered one of the most important enzymes in the viral cycle, as it is directly linked to viral replication. In addition, its synthesis is precocious in the infection process and, therefore, this enzyme is considered an important pharmacological target. Thus, the main objective of this project is to carry out the biophysical and functional characterization of the DNA polymerase complex of the MPXV virus, aiming at the search for inhibitors through the standardization of kinetic assays. It is expected, therefore, to obtain valuable information that will serve as a basis for the design of inhibitors based on the structure of this target.