Drug repositioning identifies salvinorin A and deacetylgedunin (DCG) enriched plant extracts as novel inhibitors of Mpro, RBD-ACE2 and TMPRRS2 proteins.

The coronavirus disease 2019 (COVID-19) has spread worldwide with severe health, social, and economic repercussions. Although vaccines have significantly reduced the severity of symptoms and deaths, alternative medications derived from natural products (NPs) are vital to further decrease fatalities, especially in regions with low vaccine uptake. When paired with the latest computational developments, NPs, which have been used to cure illnesses and infections for thousands of years, constitute a renewed resource for drug discovery. In the present report, a combination of computational and in vitro methods reveals the repositioning of NPs and identifies salvinorin A and deacetylgedunin (DCG) as having potential anti-SARS-CoV-2 activities. Salvinorin A was found both in silico and in vitro to inhibit both SARS-CoV-2 spike/host ACE2 protein interactions, consistent with blocking viral cell entry, and well as live virus replication. Plant extracts from Azadirachta indica and Cedrela odorata, which contain high levels of DCG, inhibited viral cell replication by targeting the main protease (Mpro) and/or inhibited viral cell entry by blocking the interaction between spike RBD-ACE2 protein at concentrations lower than salvinorin A. Our findings suggest that salvinorin A represent promising chemical starting points where further optimization may result in effective natural product-derived and potent anti-SARS-CoV-2 inhibitors to supplement vaccine efforts.

Optical and electronic properties enhancement via chalcogenides: promising materials for DSSC applications.

CONTEXT: Comparatively, metal-free sensitizers featuring the chalcogen family receive less attention despite known electronic properties for metal-chalcogenide materials. This work reports an array of optoelectronic properties using quantum chemical methods. Observed red-shifted bands within the UV/Vis to NIR regions with absorption maxima > 500 nm were consistent with increasing chalcogenide size. There is a monotonic down-shift in the LUMO and ESOP energy consistent with O 2p, S 3p, Se 4p, to Te 5p atomic orbital energies. Excited-state lifetime and charge injection free energies follow the decreasing order of chalcogenide electronegativity. Adsorption energies of dyes on TiO2 anatase (101) range between - 0.08 and - 0.77 eV. Based on evaluated properties, selenium- and tellurium-based materials show potential use in DSSCs and futuristic device applications. Therefore, this work motivates continued investigation of the chalcogenide sensitizers and their application. METHODS: The geometry optimization was performed at B3LYP/6-31 + G(d,p) and B3LYP/LANL2DZ level of theory for lighter and heavier atoms, respectively, using Gaussian 09. The equilibrium geometries were confirmed by the absence of imaginary frequencies. Electronic spectra were obtained at CAM-B3LYP/6-31G + (d,p)/LANL2DZ level of theory. Adsorption energies for dyes on a 4 × 5 supercell TiO2 anatase (101) were obtained using VASP. The dye-TiO2 optimizations were employed using GGA and PBE with the PAW pseudo-potentials. The energy cutoff was set at 400 eV and convergence threshold for self-consistent iteration was set to 10-4, and van der Waals were accounted using DFT-D3 model and on-site Coulomb repulsion potential set at 8.5 eV for Ti.

Hydrophobic π-π stacking interactions and hydrogen bonds drive self-aggregation of luteolin in water.

Luteolin is a flavonoid obtained from different plant species. It is known for its versatile biological activities. However, the beneficial effects of luteolin have been limited to small concentrations as a result of poor water solubility. This study aimed at investigating the hydrophobic interaction and hydration of luteolin towards the improvement of its solubility when used as a drug. We report the aggregation properties of luteolin in water by varying the number of monomers using atomistic molecular dynamics simulation. Results show that the equilibrium structure of luteolin occurs in an aggregated state with different structural arrangements. As the monomers size increase, the antiparallel flipped conformation dominates over T-shaped antiparallel, T-shaped parallel, and antiparallel conformations. The formation of intramolecular hydrogen bonding of 0.19 nm between the keto-enol groups results in hydrophobic characteristics. A larger cluster exhibits slow hydrogen bond dynamics for luteolin-luteolin than luteolin-water interaction. Water structure at large cluster size exhibited slow dynamics and low self-diffusion of luteolin. The existence of hydrophobic π-π and hydrogen bonds between luteolin molecules drives strong self-aggregation resulting in poor water solubility. Breakage of these established interactions would result in increased solubility of luteolin in water.

Luteolin: a blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics.

Natural products have served human life as medications for centuries. During the outbreak of COVID-19, a number of naturally derived compounds and extracts have been tested or used as potential remedies against COVID-19. Tetradenia riparia extract is one of the plant extracts that have been deployed and claimed to manage and control COVID-19 by some communities in Tanzania and other African countries. The active compounds isolated from T. riparia are known to possess various biological properties including antimalarial and antiviral. However, the underlying mechanism of the active compounds against SARS-CoV-2 remains unknown. Results in the present work have been interpreted from the view point of computational methods including molecular dynamics, free energy methods, and metadynamics to establish the related mechanism of action. Among the constituents of T. riparia studied, luteolin inhibited viral cell entry and was thermodynamically stable. The title compound exhibit residence time and unbinding kinetics of 68.86 ms and 0.014 /ms, respectively. The findings suggest that luteolin could be potent blocker of SARS-CoV-2 cell entry. The study shades lights towards identification of bioactive constituents from T. riparia against COVID-19, and thus bioassay can be carried out to further validate such observations.

Ensemble-based screening of natural products and FDA-approved drugs identified potent inhibitors of SARS-CoV-2 that work with two distinct mechanisms.

The recent outbreak of SARS-CoV-2 is responsible for high morbidity and mortality rate across the globe. This requires an urgent identification of drugs and other interventions to overcome this pandemic. Computational drug repurposing represents an alternative approach to provide a more effective approach in search for COVID-19 drugs. Selected natural product known to have antiviral activities were screened, and based on their hits; a similarity search with FDA approved drugs was performed using computational methods. Obtained drugs from similarity search were assessed for their stability and inhibition against SARS-CoV-2 targets. Diosmin (DB08995) was found to be a promising drug that works with two distinct mechanisms, preventing viral replication and viral fusion into the host cell. Isoquercetin (DB12665) and rutin (DB01698) work by inhibiting viral replication and preventing cell entry, respectively. Our analysis based on molecular dynamics simulation and MM-PBSA binding free energy calculation suggests that diosmin, isoquercetin, rutin and other similar flavone glycosides could serve as SARS-CoV-2 inhibitor, hence an alternative solution to treat COVID-19 upon further clinical validation.

Effects of heteroatoms in π-conjugated linkers on the optical and electronic properties of modified triphenylamine based dyes: towards DSSCs' applications.

Optoelectronic properties of triphenylamine dyes arising from the embedded five-membered π-linkers C4H4X (X = O, NH, S, Se, Te) and varying anchoring groups, cyanoacrylic acid and hydantoin, in D-π-π-A model are examined. The reported properties for both, isolated dyes and dye@TiO2 complexes, are realized through density functional theory (DFT) and time-dependent DFT. The study reveals that chalcogen doping (X = S, Se, Te) enhances absorption and fluorescent emission spectra in the visible and NIR regions. The adsorption of the dyes on the TiO2 cluster has been simulated. Alteration of the UV-Vis spectra and electron density redistribution for the complexes from individual dyes are examined and analyzed. The binding energies relate to the nature of the heteroatoms X; the complexes dye@TiO2 with heavier heteroatoms Se and Te demonstrate stronger binding. Graphical abstract.

Tuning optoelectronic properties of triphenylamine based dyes through variation of pi-conjugated units and anchoring groups: A DFT/TD-DFT investigation.

Dye-sensitized solar cells (DSSCs) have attracted widespread attention due to their unique features. In the present work, molecular engineered triphenylamine based dyes featuring donor-bridge-acceptor architecture have been considered and investigated for suitable properties for DSSCs applications. Hydantoin anchoring group has been introduced replacing the commonly used cyanoacrylic acid to improve the long-term stability of the device. Results on the effects of varied anchoring groups and pi-spacers have been interpreted from the viewpoint of DFT/TD-DFT calculations. Designed sensitizers exhibit suitable light-harvesting efficiencies, excited-state lifetimes, electron injection and regeneration abilities. Red-shifted electronic spectra are observed for three hydantoin dyes compared to others in the same family. Further analysis of chemical descriptors and observation from full-electron donor-acceptor map reveal that the three dyes among nine are potential materials with promising properties towards improving DSSCs performance.

Novel Xanthate Complexes for the Size-Controlled Synthesis of Copper Sulfide Nanorods.

We present a simple, easily scalable route to monodisperse copper sulfide nanocrystals by the hot injection of a series of novel copper(I) xanthate single-source precursors [(PPh3)2Cu(S2COR)] (R = isobutyl, 2-methoxyethyl, 2-ethoxyethyl, 1-methoxy-2-propyl, 3-methoxy-1-butyl, and 3-methoxy-3-methyl-1-butyl), whose crystal structures are also reported. We show that the width of the obtained rods is dependent on the length of the xanthate chain, which we rationalize through a computational study, where we show that there is a relationship between the ground-state energy of the precursor and the copper sulfide rod width.