Search

The pandemic that started in Wuhan (China) in 2019 has caused a large number of deaths, and infected people around the world due to the absence of effective therapy against coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2). Viral maturation requires the activity of the main viral protease (M pro ), so its inhibition stops the progress of the disease. To evaluate possible inhibitors, a computational model of the SARS-CoV-2 enzyme M pro was constructed in complex with 26 synthetic ligands derived from coumarins and quinolines. Analysis of simulations of molecular dynamics and molecular docking of the models show a high affinity for the enzyme ( ∆E binding between -5.1 and 7.1 kcal mol -1 ). The six compounds with the highest affinity show K d between 6.26 × 10 -6 and 17.2 × 10 -6 , with binding affinity between -20 and -25 kcal mol -1 , with ligand efficiency less than 0.3 associated with possible inhibitory candidates. In addition to the high affinity of these compounds for SARS-CoV-2 M pro , low toxicity is expected considering the Lipinski, Veber and Pfizer rules. Therefore, this novel study provides candidate inhibitors that would allow experimental studies which can lead to the development of new treatments for SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yañez, Osorio, Uriarte, Areche, Tiznado, Perez-Donoso, García-Beltrán and González-Nilo.)

We report a green strategy for the extraction of lichen substances from Stereocaulon glareosum . This sustainable alternative does not use volatile toxic organic solvents, but it is assisted by microwave and is checked by UHPLC/ESI/MS/MS. Ionic liquids may provide a better alternative in the extraction of natural products from lichens., (Copyright © 2020 Calla-Quispe, Robles, Areche and Sepulveda.)

It was recently shown that, when tested in cellular systems, quercetin oxidized products (Qox) have significantly better antioxidant activity than quercetin (Q) itself. The main Qox identified in the experiments are either 2,5,7,3',4'-pentahydroxy-3,4-flavandione (Fl) or its tautomer, 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2 H )-benzofuranone (Bf) . We have now performed a theoretical evaluation of different physicochemical properties using density functional theory (DFT) calculations on Q and its main Qox species. The most stable structures (for Q and Qox) were identified after a structural search on their potential energy surface. Since proton affinities (PAs) are much lower than the bond dissociation enthalpies (BDEs) of phenolic hydrogens, we consider that direct antioxidant activity in these species is mainly due to the sequential proton loss electron transfer (SPLET) mechanism. Moreover, our kinetic studies, according to transition state theory, show that Q is more favored by this mechanism. However, Qox have lower PAs than Q , suggesting that antioxidant activity by the SPLET mechanism should be a result of a balance between proclivity to transfer protons (which favors Qox) and the reaction kinetics of the conjugated base in the sequential electron transfer mechanism (which favors Q ). Therefore, our results support the idea that Q is a better direct antioxidant than its oxidized derivatives due to its kinetically favored SPLET reactions. Moreover, our molecular docking calculations indicate a stabilizing interaction between either Q or Qox and the kelch-like ECH-associated protein-1 (Keap1), in the nuclear factor erythroid 2-related factor 2 (Nrf2)-binding site. This should favor the release of the Nrf2 factor, the master regulator of anti-oxidative responses, promoting the expression of the antioxidant responsive element (ARE)-dependent genes. Interestingly, the computed Keap1-metabolite interaction energy is most favored for the Bf compound, which in turn is the most stable oxidized tautomer, according to their computed energies. These results provide further support for the hypothesis that Qox species may be better indirect antioxidants than Q , reducing reactive oxygen species in animal cells by activating endogenous antioxidants., (Copyright © 2019 Vásquez-Espinal, Yañez, Osorio, Areche, García-Beltrán, Ruiz, Cassels and Tiznado.)