Banca de QUALIFICAÇÃO: ERICA ERLANNY DA SILVA RODRIGUES

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ERICA ERLANNY DA SILVA RODRIGUES
DATE: 25/03/2022
TIME: 14:00
LOCAL: Google Meet
TITLE:

Molecular docking, synthesis and antiviral evaluation of potentially active peptidomimetics against Chikungunya virus

KEY WORDS:

Viral proteases, Neglected tropical diseases, Antivirals, Peptidomimetics, CHIKV.

PAGES: 150
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SUMMARY:

Chikungunya virus (CHIKV) is an arbovirus of the Alphavirus genus transmitted by Aedes sp. and Culex sp. mosquitoes. It is responsible for causing Chikungunya fever (CHIKF) which leads to great economic and public health impacts. Throughout history, it appears that CHIKV infections are mainly associated with developing countries, and are responsible for endemic and recurrent outbreaks. However, in recent decades, CHIKV has spread globally. In general, its clinical manifestations range from a self-limited febrile state to debilitating polyarthralgia, which has been responsible for significant impacts on the economy of the region  it affects since its symptoms can last for months or years. Such symptoms become even more severe in patients with other pre-existing diseases/comorbidities, which can lead to death. Despite advances in the search for new specific antiviral agents against CHIKV, including immunological strategies such as vaccines, current treatments are non-specific and focused on symptom relief. Different approaches have been used in the discovery and development processes of anti-CHIKV compounds such as drug repositioning, monoclonal antibodies, gene silencing, and inhibitors that target different structures of the viral cycle. In this scenario, peptidomimetics stand out as a promising chemical class in the development of new drugs since they have been reported as viral protease inhibitors, acting in submicromolar concentrations. Given the above, this work sought to develop new antiviral agents against CHIKV, acting through the inhibition of essential viral proteins during the replication cycle. For this, peptidomimetics were planned using in silico strategies and then only the most promising candidates were synthesized in solid phase using the traditional F-moc strategy with Rink Amide®️ resin. All obtained peptidomimetics were characterized by spectroscopic and spectrometric techniques and then biologically evaluated. The cytotoxic and antiviral effect on the CHIKV virus were investigated in vitro in cells susceptible to infection. To date, new tri-peptides containing Gly and Leu have been developed. In particular, the PEP12 compound (%inhibition ~45% at 10 µM) represents the most promising compound obtained in the initial investigations. Finally, the results obtained so far have allowed an increase in the knowledge of scaffolds against CHIKV and enabled the planning of new rational modifications in potential inhibitors..

BANKING MEMBERS:
Externo à Instituição - MARCELO SANTOS CASTILHO
Interno - 3182336 - EDEILDO FERREIRA DA SILVA JUNIOR
Externo ao Programa - 1612086 - ENIO JOSE BASSI
Interna - 1820117 - ISIS MARTINS FIGUEIREDO
Presidente - 1369387 - JOAO XAVIER DE ARAUJO JUNIOR