No abstract

No abstract

This study aimed to identify potential inhibitors and investigate the mechanism of action on SARS-CoV-2 ACE2 receptors using a molecular modeling study and theoretical determination of biological activity. Hydroxychloroquine was used as a pivot structure and antimalarial analogues of 1,2,4,5 tetraoxanes were used for the construction and evaluation of pharmacophoric models. The pharmacophore-based virtual screening was performed on the Molport® database (~7.9 million compounds) and obtained 313 structures. Additionally, a pharmacokinetic study was developed, obtaining 174 structures with 99% confidence for human intestinal absorption and penetration into the blood–brain barrier (BBB); posteriorly, a study of toxicological properties was realized. Toxicological predictions showed that the selected molecules do not present a risk of hepatotoxicity, carcinogenicity, mutagenicity, and skin irritation. Only 54 structures were selected for molecular docking studies, and five structures showed binding affinity (ΔG) values satisfactory for ACE2 receptors (PDB 6M0J), in which the molecule MolPort-007-913-111 had the best ΔG value of −8.540 Kcal/mol, followed by MolPort-002-693-933 with ΔG = −8.440 Kcal/mol. Theoretical determination of biological activity was realized for 54 structures, and five molecules showed potential protease inhibitors. Additionally, we investigated the Mpro receptor (6M0K) for the five structures via molecular docking, and we confirmed the possible interaction with the target. In parallel, we selected the TopsHits 9 with antiviral potential that evaluated synthetic accessibility for future synthesis studies and in vivo and in vitro tests.

Edited by J Van Staden Mosquitoes, such as Aedes aegypti and Culex quinquefasciatus, are important vectors of diseases, such as dengue fever, chikungunya fever, Zika virus, and filariasis, and these diseases are public health problems. The present study was carried out to evaluate the larvicidal activity of the hydroethanolic extract from leaves of Acmella oleracea leaves against 3rd instar larvae of the Ae. aegypti dengue vector and the Cx. quinquefasciatus filariasis vector. The hydroethanolic extract caused significant mortality in Ae. aegypti and Cx. quinquefasciatus. After 24 h of exposure to the extract, it was possible to establish the LC 50 values for the extract: 11.41 ppm for Ae. aegypti and LC 50 32.40 ppm for Cx. quinquefasciatus. The hydroethanolic extract from leaves of A. oleracea showed very low ecotoxicity suggesting that it can be used without causing environmental damage. This is the first study that shows the use of hydroethanolic extract from leaves of A. oleracea as an alternative to synthetic larvicides to eliminate larvae of Ae. aegypti and Cx. quinquefasciatus in an easy, cheap and safe way.

No abstract