Abordagem bioisostérica e de triagem virtual para identificar inibidores naturais da nsp3 do Alphavírus chikungunya

Abstract

Chikungunya fever is characterized by fever and debilitating joint pain that can progress to a chronic form. It is a disease caused by the Chikungunya virus (CHIKV) transmitted to humans through the bite of the female Aedes mosquito. This virus is a public health concern, since part of the world's population is at risk of infection. In addition to bringing negative effects to society and considerable economic losses, the symptomatological picture of CHIKV still does not have a specific drug for treatment. That said, this work aims to predict (in silico) natural compounds that have inhibitory activity against a protein that acts on the viral replication of CHIKV. The nonstructural protein 3 of the virus was used as a receptor, and 84,215 ligands obtained from the ZINC20 database. The Autodock Vina software allowed the performance of molecular docking, through the LigPlot+ and PyMol programs the interactions and structures were observed; The pkCSM server was suitable for analyzing the pharmacokinetic characteristics of the compounds, enabling the prediction of factors such as absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Finally, Bioisosterism was performed through the MolOpt server to improve the pharmacokinetics and performance of the identified natural compounds. At the end of the analyses, three bioisosteres were obtained, Chikv_bio1, Chikv_bio2, Chikv_bio3, which contemplate good binding energies, ideal pharmacokinetics, and interact with the active site of the protein, being considered potential inhibitory compounds of nsP3. Furthermore, in vitro and in vivo tests are necessary to confirm the predictive results presented here, ensuring continuity in the search for an effective drug in the treatment of Chikungunya, a disease that affects part of the population and directly impacts the quality of life of patients.