Designing Sars-Cov-2 Mono-ADP-ribosyl hydrolase Enzyme Inhibitors: A New Class of Antiviral Agents?

• Grant number: 21/10124-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2022
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Nicolas Carlos Hoch
• Grantee: Isaac de Araujo Matos
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/18007-5 - Protein ADP-ribosylation: DNA damage signalling and impacts on human health, AP.JP
• Associated scholarship(s): 22/14895-9 - Validation of putative SARS-CoV-2 macrodomain inhibitors obtained by virtual screening, BE.EP.PD

Abstract

The virus that causes severe acute respiratory syndrome 2 (SARS-CoV-2) has triggered one of the biggest pandemics seen by humanity, leading to millions of deaths worldwide. Although the development of vaccines has taken place in record time and has provided a substantial reduction in the number of deaths from COVID-19, the development of drugs with antiviral activity remains a necessity, for example to treat non-vaccinated individuals, in cases of emergence of new SARS-CoV-2 variants that are insufficiently contained by current vaccines, or to be better prepared for the emergence of future pandemics caused by new emerging viruses. SARS-CoV-2 mono-ADP-ribosyl hydrolase (macrodomain) is an attractive molecular target, as it is an essential enzyme for viral replication and suppression of the host's immune response. Thus, the general objective of this project is the planning of inhibitors of the SARS-Cov-2 macrodomain using virtual screening followed by validation through enzymatic, spectroscopic and cellular assays, enabling the continuity of the participation of a Brazilian group in an international collaboration for the development of a new antiviral therapeutic class.

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)

WOELLNER-SANTOS, DAISY; TAHIRA, ANA C.; MALVEZZI, JOAO V. M.; MESEL, VINICIUS; MORALES-VICENTE, DAVID A.; TRENTINI, MONALISA M.; MARQUES-NETO, LAZARO M.; MATOS, ISAAC A.; KANNO, ALEX I.; PEREIRA, ADRIANA S. A.; et al. Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques. NPJ VACCINES, v. 9, n. 1, p. 19-pg., 2024-01-04. (18/18117-5, 20/01917-9, 21/10124-5, 15/06366-2, 19/02305-0, 16/10046-6, 19/09404-3)