Estudo in silico das interações em potencial entre flavonoides e alvos proteicos na infecção dos SARS-COV-2

Abstract

The COVID - 19 pandemic, which originated in the Chinese city of Wuhan in China, it has quickly spread worldwide and it has become an unprecedented public health problem. The consequences are reflected on the numbers of new cases and deaths that grows daily, highlighting the search for therapeutic approaches to curb the spread of the virus, such as natural products. In this context, flavonoids are polyphenolic compounds from the secondary metabolism of plants, which are highlighted in a current scenario where the availability of antiviral alternatives is reduced. Its biological actions in the face of a multitude of diseases and microorganisms are well described in the literature. Based on these findings, the work evaluated, through molecular docking assays, the interactions between flavonoids and structural and enzymatic targets of SARS-COV-2, in addition to the angiotensin-converting enzyme 2 (ACE2) that allows virus entry into cells host. In front of the main proteinase (Mpro), the flavanone hesperedin was the only compound to demonstrate the same coupling pattern as the natural inhibitor N3, while the other compounds tested showed excellent affinity scores. In addition, the natural compounds were able to interact with the NSP16-NSP10 heterodimer methyltransferase enzyme complex (Mt) in the same region as the inhibitor sinefungin. The interaction with the angiotensin-converting enzyme 2 (ACE2) occurred at the same site as the inhibitor lisinopril with variable affinities. These data suggest that flavonoids are capable of interfering in SARS-COV-2 replication and infection processes through the inhibition of posttranslational modifications of structural proteins and the interaction of the viral particle with the host cell, evidencing the theoretical pharmacological potential and the viability of these molecules for in vitro tests.