Estudos de docagem e dinâmica molecular de vitanolídeos de Athenaea velutina: potenciais inibidores da protease principal do SARS-CoV-2

Abstract

The global COVID-19 pandemic has led the scientific community to dedicate its efforts to finding effective antivirals capable of treating or minimizing the effects caused by the SARS-CoV-2 coronavirus. In this context, some targets can be chosen to test the inhibition potential of the substances studied, mainly the Principal Protease (Mpro), which is essential for the viral translation and transcription processes. Many natural compounds are being investigated for drug development because plants and natural products are crucial in medicine. Among these compounds, we can mention the withanolides, a class of steroidal lactones, which have shown positive results as inhibitors of Mpro and other essential targets for the viral cycle. In this work, a new withanolide (1), together with the already known 27-deoxywithaferin A (2) and 2,3-dihydro-27-deoxywithaferin A (3), isolated from the 1:1 hexane/ethyl acetate extract of Athenaea velutina (Solanaceae), unlike withanolide D (4), which was previously isolated from the leaves of Acnistus arborescens (Solanaceae). The structures of the withanolides were determined using spectroscopic data analysis (NMR, IR, HRESIMS). In addition, docking and molecular dynamics studies were performed on the antiviral activities of withanolides 1 – 4 against Mpro. Based on the results, compound 1 showed the best numbers regarding Mean Square Deviation of Atomic Positions (RMSD) and interaction energies.