Structural characterization of SARS-CoV-2 coronavirus proteins, the causative agent of the infectious disease COVID-19, and search for antiviral drugs

Abstract

Emerging and reemerging viruses will always constitute a threat and a challenge to global public health. The emergence of a new type of coronavirus (SARS-CoV-2) in December 2019 has spawned an epidemic that is currently underway resulting in more than 227,000 cases and more than 9,000 deaths. Despite the efforts made with the current epidemic and the past outbreaks (SARS and MERS) in the development of antivirals, no compound has been shown to be effective in clinical trials. Thus, this project has the central objective of using structural information from SARS-CoV-2 proteins to assist in the search for molecules that can be progressed in the clinical development of specific antiviral drugs for this virus. For this, the production and characterization of nonstructural proteins (nsps) involved in the viral replication process will be conducted, such as the protease Mpro nsp5, the RNA polymerase RdRp nsp12, the RNA helicase nsp13, the exoribonuclease nsp14 and the endoribonuclease nsp15. From these samples, we intend to use a combination of biophysical and biochemical techniques for the identification of new candidates for antivirals using the Structure-Based Drug Discovery (SBDD) methods. In this way, we intend to obtain a potential drug candidate, which can be used in pre-clinical tests. This project is linked to the project 2020/04602-9 approved at the FAPESP COVID-19 call for proposals. (AU)