Search for antiviral drugs, targeting RNA-dependent RNA polymerases (RdRp) from the Alphavirus Chikungunya (NSP4) and Beta-Coronavirus SARS-CoV-2 (NSP12)

Abstract

Emerging and reemerging viruses will always constitute a threat and a challenge to global public health. Despite the recent COVID-19 pandemic highlight, the emergence of diseases caused by viral agents is not a new phenomenon. In Brazil, for at least 30 years, there has been the emergence and re-emergence of viral diseases, caused mainly by arboviruses, such as the Chikungunya epidemic that began in 2014 and is still ongoing. The COVID-19 pandemic, which began in December 2019, posed additional challenges to scientific research and health services. In Brazil, there were records of a significant increase in cases of Chikungunya, Dengue and Zika in the first half of 2020. This epidemiological scenario, of simultaneous viral infections, represents a risk of mistaken health actions, in addition to the possibility of coinfections. Therefore, efforts in basic research, in search of vaccines and antiviral agents, must happen quickly, attacking different viruses simultaneously. Thus, has as its main objective the use of structural biology as a tool in the search for molecules that can help in the development of specific antiviral drugs targeting RNA-dependent RNA polymerases (RdRp), respectively from CHIKV (NSP4) and SARS -CoV-2 (NSP12). For this, it will be necessary to produce these enzymes in recombinant form, which will then be explored through biophysical and biochemical strategies for the identification and/or planning of inhibitors through the Structure-Based Drug Discovery (SBDD) and Fragment Based Drug Discovery (FBDD) methods, aimed at discovering potential drug candidate that can be used in pre-clinical studies against the Chikungunya Fever and COVID-19. This project is linked to the FAPESP's CIBFar/CEPID project. (AU)