Search for inhibitory compounds of Uracil DNA Glycosylase from the Monkeypox Virus (MPXV)

• Grant number: 24/18105-8
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 07, 2025
• End date: February 26, 2025
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Glaucius Oliva
• Grantee: Felipe Alves Clarindo
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

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. Following this, there was a rapid spread of the disease in other countries. So far (Sept/2024), there are 107,725 confirmed cases worldwide, with 11,841 cases in Brazil alone. Transmission of MPXV typically occurs between people or wild animals through contact with lesions, body fluids, respiratory droplets, or contaminated materials. To date, a single drug, Tecovirimat, has been used on an emergency basis to combat monkeypox. Although it was approved in 2022 by European, Brazilian, and American health authorities, data from studies in animals and humans are still not fully available, and several aspects, such as potential complications, dosage, and long-term sequelae, still need to be evaluated. The Monkeypox virus has a genome of 197 kb, belongs to the Orthopoxvirus genus, Poxviridae 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 because it is directly linked to replication. Additionally, its synthesis is early in the infection process, making it an important pharmacological target. Thus, the main objective of this work is to search, among the libraries available in our laboratory, for compounds capable of inhibiting the enzyme Uracil DNA glycosylase, one of the enzymes participating in the MPXV replication complex formed by DNApol.