Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs

The pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has stimulated the search for antivirals to tackle COVID-19 infection. Molecules with known pharmacokinetics and already approved for human use have been demonstrated or predicted to be suitable to be used either directly or as a base for a scaffold-based drug design. Among these substances, quercetin is known to be a potent in vitro inhibitor of 3CLpro, the SARS-CoV-2 main protease. However, its low in vivo bioavailability calls for modifications to its molecular structure. In this work, this issue is addressed by using rutin, a natural flavonoid that is the most common glycosylated conjugate of quercetin, as a model. Combining experimental (spectroscopy and calorimetry) and simulation techniques (docking and molecular dynamics simulations), we demonstrate that the sugar adduct does not hamper rutin binding to 3CLpro, and the conjugated compound preserves a high potency (inhibition constant in the low micromolar range, Ki = 11 μM). Although showing a disruption of the pseudo-symmetry in the chemical structure, a larger steric volume and molecular weight, and a higher solubility compared to quercetin, rutin is able to associate in the active site of 3CLpro, interacting with the catalytic dyad (His41/Cys145). The overall results have implications in the drug-design of quercetin analogs, and possibly other antivirals, to target the catalytic site of the SARS-CoV-2 3CLpro.

Combining Theory and Experiment for Understanding of Ultrafast Photoinduced Charge-Transfer Processes

This article gives a brief overview of the longstanding collaboration between our experimental spectroscopy group in Geneva and the theoretical group lead by Prof. A.I. Ivanov in Volgograd. This fruitful collaboration resulted in a significant increase of our understanding of the dynamics of several ultrafast chargetransfer processes in the condensed phase.

Quantum chemical calculation of NIR spectra of practical materials

In the third issue of the series on modern quantum chemical methods in the support role of NIR spectroscopy we continue to introduce the researchers from the field of experimental spectroscopy to practical aspects and applications of modern anharmonic theoretical approaches. The first two issues focused on explaining the necessary theoretical and practical background, allowing readers to get more familiar with the topic. An overview of recent literature reports highlighted the advantages stemming from using quantum chemical calculation in the support role to NIR spectroscopy. These deliberations were based on several cases of small- to medium-sized molecules. This part overviews the topic of applications of quantum theoretical methods to complex molecules with practical significance, which typically prove to be challenging objects for theoretical studies. An exemplary application of presented methodology to the case of Rosmarini folium biological samples is also examined here. The rosemary specific active compound, rosmarinic acid, is a relatively complex polyphenol with growing phytopharmaceutical importance, and therefore provides an excellent object of applied studies. The possibilities of combining the information stemming from quantum chemical calculation with the methods of advanced spectral data analysis, which are commonly used in experimental NIR spectroscopy (chemometrics, two-dimensional (2D) correlation spectra) are also overviewed. Again, these deliberations are based directly on the most recent reports published in the field.

Experimental and theoretical studies on compositions, structures, and IR and NMR spectra of functionalized protic ionic liquids

DMCEAP and DMEOAP are composed of neutral and ionized species in the liquid phase as investigated through experimental spectroscopy and DFT calculations.

Laboratory and theoretical work applied to planetary atmospheres

We look at applications of recent work in theoretical and experimental spectroscopy for the analysis of IR data concerning giant planets, Titan and possibly exoplanets.

Precise Determination of Band Gap Naturally via Absorption/Reflectance/Transmission Spectra

A set of nonlinear equations about the band gap and the indexnof material property with the absorptance, reflectance and transmittance were produced based on Tauc relation. Optimizing fitting the experimental spectroscopy data, such as absorption, reflection and transmission, the band gapand the indexnrelated to the material property could be obtained accurately and reliably. Meanwhile, the experimental data were used as more as possible, and the artificial errors at pre-determining the indexnwere avoided. The lowest correlation coefficient and the largest average relative error between the experimental and the calculated data are 0.9588 and 2.7% in all considered cases respectively. The best results show the band gap obtained from this method is more accurate, easier and faster than traditional extrapolation. Hence, this work would promote the precision and reliability for predicting the band gap and index of materials naturally.

Glycan synthesis, structure, and dynamics: A selection

Glycan structural information is a prerequisite for elucidation of carbohydrate function in biological systems. To this end we employ a tripod approach for investigation of carbohydrate 3D structure and dynamics based on organic synthesis; different experimental spectroscopy techniques, NMR being of prime importance; and molecular simulations using, in particular, molecular dynamics (MD) simulations. The synthesis of oligosaccharides in the form of glucosyl fluorides is described, and their use as substrates for the Lam16A E115S glucosyl synthase is exemplified as well as a conformational analysis of a cyclic β-(1→3)-heptaglucan based on molecular simulations. The flexibility of the N-acetyl group of aminosugars is by MD simulations indicated to function as a gatekeeper for transitions of glycosidic torsion angles to other regions of conformational space. A novel approach to visualize glycoprotein (GP) structures is presented in which the protein is shown by, for example, ribbons, but instead of stick or space-filling models for the carbohydrate portion it is visualized by the colored geometrical figures known as CFG representation in a 3D way, which we denote 3D-CFG, thereby effectively highlighting the sugar residues of the glycan part of the GP and the position(s) on the protein.