Chemical Characterization and Leishmanicidal Activity In Vitro and In Silico of Natural Products Obtained from Leaves of Vernonanthura brasiliana (L.) H. Rob (Asteraceae).

Vernonanthura brasiliana (L.) H. Rob is a medicinal plant used for the treatment of several infections. This study aimed to evaluate the antileishmanial activity of V. brasiliana leaves using in vitro and in silico approaches. The chemical composition of V. brasiliana leaf extract was determined through liquid chromatography-mass spectrometry (LC-MS). The inhibitory activity against Leishmania amazonensis promastigote was evaluated by the MTT method. In silico analysis was performed using Lanosterol 14alpha-demethylase (CYP51) as the target. The toxicity analysis was performed in RAW 264.7 cells and Tenebrio molitor larvae. LC-MS revealed the presence of 14 compounds in V. brasiliana crude extract, including flavonoids, flavones, sesquiterpene lactones, and quinic acids. Eriodictol (ΔGbind = -9.0), luteolin (ΔGbind = -8.7), and apigenin (ΔGbind = -8.6) obtained greater strength of molecular interaction with lanosterol demethylase in the molecular docking study. The hexane fraction of V. brasiliana showed the best leishmanicidal activity against L. amazonensis in vitro (IC50 12.44 ± 0.875 µg·mL-1) and low cytotoxicity in RAW 264.7 cells (CC50 314.89 µg·mL-1, SI = 25.30) and T. molitor larvae. However, the hexane fraction and Amphotericin-B had antagonistic interaction (FICI index ≥ 4.0). This study revealed that V. brasiliana and its metabolites are potential sources of lead compounds for drugs for leishmaniasis treatment.

Plant Metabolites as SARS-CoV-2 Inhibitors Candidates: In Silico and In Vitro Studies.

Since it acquired pandemic status, SARS-CoV-2 has been causing all kinds of damage all over the world. More than 6.3 million people have died, and many cases of sequelae are in survivors. Currently, the only products available to most of the world's population to fight the pandemic are vaccines, which still need improvement since the number of new cases, admissions into intensive care units, and deaths are again reaching worrying rates, which makes it essential to compounds that can be used during infection, reducing the impacts of the disease. Plant metabolites are recognized sources of diverse biological activities and are the safest way to research anti-SARS-CoV-2 compounds. The present study computationally evaluated 55 plant compounds in five SARS-CoV-2 targets such Main Protease (Mpro or 3CL or MainPro), RNA-dependent RNA polymerase (RdRp), Papain-Like Protease (PLpro), NSP15 Endoribonuclease, Spike Protein (Protein S or Spro) and human Angiotensin-converting enzyme 2 (ACE-2) followed by in vitro evaluation of their potential for the inhibition of the interaction of the SARS-CoV-2 Spro with human ACE-2. The in silico results indicated that, in general, amentoflavone, 7-O-galloylquercetin, kaempferitrin, and gallagic acid were the compounds with the strongest electronic interaction parameters with the selected targets. Through the data obtained, we can demonstrate that although the indication of individual interaction of plant metabolites with both Spro and ACE-2, the metabolites evaluated were not able to inhibit the interaction between these two structures in the in vitro test. Despite this, these molecules still must be considered in the research of therapeutic agents for treatment of patients affected by COVID-19 since the activity on other targets and influence on the dynamics of viral infection during the interaction Spro x ACE-2 should be investigated.