Extraction of rutin from tagetes erecta (Marigold) and preparation of peroral nano-suspension for effective antitussive/expectorant therapy

The present study narrates the extraction of rutin from Tagetes erecta (Marigold) via maceration followed by ultrasonication. The extracted rutin was further fabricated into nanoparticles by high-pressure homogenization (HPH) and assessed by HPLC, DSC, XRD, TEM, and FTIR spectroscopy. The optimized batch of nanoparticles obtained using 32 central composite design (CCD) which exhibited particle size 209±14 nm, PDI 0.234±0.06, and 92±1.3% entrapment efficiency. The lyophilized rutin nanoparticles were further converted into nano-suspension. Interestingly, the rutin nano-suspension exhibited a similar antitussive effect in vivo as that by standard treatment pentoxyverine and reduced the coughing times within 2 min. Also, the phlegm showed high UV absorbance, implying its better expectorant activity than the standard and control. The rutin nano-suspension was highly stable and shelf life was found to be ∼29.1 months. The present study, for the first time, paves a way for the use of rutin nano-suspension to overcome chest congestion, shortening of breath, and in the management of cough.

Extraction of Antioxidant Compounds from Brazilian Green Propolis Using Ultrasound-Assisted Associated with Low- and High-Pressure Extraction Methods.

The demand for bee products has been growing, especially regarding their application in complementary medicine. Apis mellifera bees using Baccharis dracunculifolia D.C. (Asteraceae) as substrate produce green propolis. Among the examples of bioactivity of this matrix are antioxidant, antimicrobial, and antiviral actions. This work aimed to verify the impact of the experimental conditions applied in low- and high-pressure extractions of green propolis, using sonication (60 kHz) as pretreatment to determine the antioxidant profile in the extracts. Total flavonoid content (18.82 ± 1.15-50.47 ± 0.77 mgQE·g-1), total phenolic compounds (194.12 ± 3.40-439.05 ± 0.90 mgGAE·g-1) and antioxidant capacity by DPPH (33.86 ± 1.99-201.29 ± 0.31 µg·mL-1) of the twelve green propolis extracts were determined. By means of HPLC-DAD, it was possible to quantify nine of the fifteen compounds analyzed. The results highlighted formononetin (4.76 ± 0.16-14.80 ± 0.02 mg·g-1) and p-coumaric acid (

Introduction pages, Notulae Scientia Biologicae 14(3), 2022

Notulae Scientia Biologicae (http://www.notulaebiologicae.ro), Issue 3, Volume 14, 2022: The papers published in this issue represent interesting novelties in different topics of life science. Among the exciting research or reviews, we invite readers to find news about: Micropropagation and potential of bioactive compounds of saffron (Crocus sativus L.) for nutrition and health;Anatomical, physiological, biochemical and molecular responses of Eucalyptus spp. under water deficit conditions and characteristics of Tunisian arid species;Escherichia coli infection, a negative prognostic factor on the evolution of patients with surgical diseases;Biological characteristics and mortality in patients with diabetes and COVID-19;The influence of Staphylococcus infections on the evolution of hospitalized patients: The experience of the surgical department of IRGH Cluj-Napoca;Parquetina nigrescens leaf infusion: a food-based approach for the management of diet-induced iron deficiency in weanling rats;Evaluation of the effects of calabash chalk on the haematological profile of Wistar rats;Inhibitory potential of rutin on lipopolysaccharide-induced toxicity and inflammatory response of raw U937 cells and macrophages;Hypoglycemic and in vitro antioxidant activities of Stereospermum kunthianum stem bark hydromethanol extract;Polyploidization and speciation: patterns of natural hybridization and gene flow in basil (Ocimum spp.);Increasing liana biomass and carbon stocks in tropical dry evergreen forests of southern India.

Phytochemicals As a Potential Inhibitor of COVID-19: An In-Silico Perspective

The current research has centered on the use of pharmacological and binding affinity methods to test the 36 compounds as bioactive constituents’ inhibitors for COVID-19. Six compounds out of 36 phytoconstituents (rutin, quercetin, catechin gallate, rhamnetin, campesterol and stigmasterol) have demonstrated outstanding molecular docking and drug-like properties as HIV inhibitors Lopinavir and Indinavir. Interestingly, the lowest binding energies (LBE) and the inhibition constant (Ki) have showed that these compounds are able to bind to the P-glycoprotein substrate of 3CLpro and Nsp15. Interestingly, rutin has been found to be an excellent potential inhibitor for COVID-19 proteins because it has the best LBE score and Ki value than those of other compounds, and of its ability to form strong H-bonds with COVID-19 proteins. The compounds that come next to the rutin compound are stigmasterol and campesterol. As a result, these compounds are considered possible novel inhibitors of COVID-19. In order to validate the computational results, more in vitro and in vivo investigations are required to support the findings of this research.

In vitro antiviral effect of Mexican and Brazilian propolis and phenolic compounds against human coronavirus 229E.

Propolis is a resinous substance collected by bees (Apis mellifera). It is used for its biological properties. This natural product is available as a safe therapeutic option. Herein, we report the antiviral effects of brown propolis extract from Mexico and green and red propolis extracts from Brazil, as well as their phenolic compounds (quercetin, caffeic acid, and rutin) in preventing infection of MRC-5 cells by HCoV-229E. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. All samples studied showed antiviral activity. Green and brown propolis extracts, and quercetin exhibited the best EC50 values with values of 19.080, 11.240, and 77.208 µg/mL against HCoV-229E, respectively, and with TC50 of 62.19, 29.192, and 298 µg/mL on MRC-5 cells, respectively. These results are the first in vitro study of the effects of propolis on HCoV-229E and provide the basis for the development of natural formulations against other coronavirus strains.

Computational screening of natural compounds from Salvia plebeia R. Br. for inhibition of SARS-CoV-2 main protease.

The novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has emerged to be the reason behind the COVID-19 pandemic. It was discovered in Wuhan, China and then began spreading around the world, impacting the health of millions. Efforts for treatment have been hampered as there are no antiviral drugs that are effective against this virus. In the present study, we have explored the phytochemical constituents of Salvia plebeia R. Br., in terms of its binding affinity by targeting COVID-19 main protease (Mpro) using computational analysis. Molecular docking analysis was performed using PyRx software. The ADMET and drug-likeness properties of the top 10 compounds showing binding affinity greater than or equal to - 8.0 kcal/mol were analysed using pkCSM and DruLiTo, respectively. Based on the docking studies, it was confirmed that Rutin and Plebeiosides B were the most potent inhibitors of the main protease of SARS-CoV-2 with the best binding affinities of - 9.1 kcal/mol and - 8.9 kcal/mol, respectively. Further, the two compounds were analysed by studying their biological activity using the PASS webserver. Molecular dynamics simulation analysis was performed for the selected protein-ligand complexes to confirm their stability at 300 ns. MM-PBSA provided the basis for analyzing the affinity of the phytochemicals towards Mpro by calculating the binding energy, and secondary structure analysis indicated the stability of protease structure when it is bound to Rutin and Plebeiosides B. Altogether, the study identifies Rutin and Plebeiosides B to be potent Mpro inhibitors of SARS-CoV-2. Supplementary Information: The online version contains supplementary material available at 10.1007/s42535-021-00304-z.

Investigation on chemical composition, antioxidant activity and SARS-CoV-2 nucleocapsid protein of endemic Ferula longipedunculata pesmen

The essential and fatty oils were investigated and a quantitative analysis of the root, green and stem parts of F. Longipedunculata was performed by GC-MS and HPLC-TOF/MS and their antioxidant (DPPH method) activities and potential binding of phytochemicals against SARS-CoV-2 nucleocapsid were determined using Molegro Virtual Docker software. In the root part of the plant, the prominent components of oil were beta-phellandrene (53.46%), ocimene (6.79%), 4-terpineol (5.94%) and santalol (5.03%). According to the quantitative results, vanillic acid (141.35 mg/kg), ferulic acid (126.19 mg/kg) and 4-hydroxybenzoic acid (119.92 mg/kg) were found in the roots;quercetin-3-beta-O-glycoside (1737.70 mg/kg), quercetin (531.35 mg/kg) and ferulic acid (246.22 mg/kg) were found in the in the green part;and fumaric acid (2100.21 mg/kg), quercetin-3-beta-O-glycoside (163.24 mg/kg), vanillic acid (57.59 mg/kg) were detected in the stem part. The antioxidant activity of all parts of the plant was higher than the control with BHT. Silibinin, rutin, and neohesperidin exhibited a stronger affinity than nucleotides. In the silico analysis, many of the phytochemicals were attached with strong hydrogen-bonds and electrostatic effects to the amino acids to which nucleotides are bound. The results indicated that the plant showed antioxidant effects and can be effective against SARS-CoV-2 thanks to the different phytochemical compounds it contains.

Flavonols and dihydroflavonols inhibit the main protease activity of SARS-CoV-2 and the replication of human coronavirus 229E.

Since December 2019, the deadly novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 pandemic. To date, vaccines are available in the developed countries to prevent the infection of this virus; however, medicines are necessary to help control COVID-19. Human coronavirus 229E (HCoV-229E) causes the common cold. The main protease (Mpro) is an essential enzyme required for the multiplication of these two viruses in the host cells, and thus is an appropriate candidate to screen potential medicinal compounds. Flavonols and dihydroflavonols are two groups of plant flavonoids. In this study, we report docking simulation with two Mpro enzymes and five flavonols and three dihydroflavonols, in vitro inhibition of the SARS-CoV-2 Mpro, and in vitro inhibition of the HCoV 229E replication. The docking simulation results predicted that (+)-dihydrokaempferol, (+)- dihydroquercetin, (+)-dihydromyricetin, kaempferol, quercetin, myricentin, isoquercitrin, and rutin could bind to at least two subsites (S1, S1', S2, and S4) in the binding pocket and inhibit the activity of SARS-CoV-2 Mpro. Their affinity scores ranged from -8.8 to -7.4 (kcal/mol). Likewise, these compounds were predicted to bind and inhibit the HCoV-229E Mpro activity with affinity scores ranging from -7.1 to -7.8 (kcal/mol). In vitro inhibition assays showed that seven available compounds effectively inhibited the SARS-CoV-2 Mpro activity and their IC50 values ranged from 0.125 to 12.9 µM. Five compounds inhibited the replication of HCoV-229E in Huh-7 cells. These findings indicate that these antioxidative flavonols and dihydroflavonols are promising candidates for curbing the two viruses.

Study on the mechanism of Lianhua Qingwen capsule absorbed components in prevention and treatment of COVID-19 by intervening on cytokines storm based on network pharmacology and molecular docking

To analyze the possible mechanism of the intervention of absorbed components of Lianhua Qingwen Capsule on COVID-19 from the perspective of cytokine storm based on network pharmacology and molecular docking. Through literature mining, the components of Lianhua Qingwen capsules into blood were determined, and the related action targets of the components were searched by TCMSP and BATMAN-TCM databases. The related targets of COVID-19 and cytokine storm were screened by GeneCards, OMIM and Drugbank databases. The protein interaction PPI network was constructed through String database. DAVID database was used for GO analysis and KEGG pathway analysis. Cytoscape 3.8.0 software was used to build the network diagram. Molecular docking was performed by AutoDock software.In addition, multiple organ tissue injury, immune injury and SARS related targets were retrieved and intersected with cytokine storm.A total of 17 absorbed components of Lianhua Qingwen Capsules were collected, 237 corresponding targets and 47 targets intersected with diseases obtained, and 22 core targets screened out.GO analysis and KEGG pathway analysis presented 174 entries and 83 entries respectively (P < 0.01). The molecular docking results showed that the compounds of Emodin, Formononetin, Rutin, Gallic acid, Liquiritigenin had good binding ability with the core target of AKT1, IL-6, TP53, JUN, TNF. The proportion of intersecting target of Lianhua Qingwen Capsule and multiple organ tissue injury and immune injury was 1.6%-2.0%, and the proportion of intersecting target and SARS was 4.3%. Absorbed components of Lianhua Qingwen Capsule could effectively prevent and treat COVID-19 by intervening cytokine storm through multi-component, multi-target and multi-pathway synergistic action, and its mechanism may be related to antigen-scavenging, immune-regulating and tissue and organ protection.

Potential Effects of Romanian Propolis Extracts against Pathogen Strains.

The impact of globalization on beekeeping brings new economic, scientific, ecological and social dimensions to this field The present study aimed to evaluate the chemical compositions of eight propolis extracts from Romania, and their antioxidant action and antimicrobial activity against seven species of bacteria, including pathogenic ones: Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Listeria monocytogenes and Salmonella enterica serovar Typhimurium. The phenolic compounds, flavonoids and antioxidant activity of propolis extracts were quantified; the presence of flavones and aromatic acids was determined. Quercetin and rutin were identified by HPLC analysis and characterized using molecular descriptors. All propolis samples exhibited antibacterial effects, especially against P. aeruginosa and L. monocytogenes. A two-way analysis of variance was used to evaluate correlations among the diameters of the inhibition zones, the bacteria used and propolis extracts used. Statistical analysis demonstrated that the diameter of the inhibition zone was influenced by the strain type, but no association between the propolis origin and the microbial activity was found.

Berberis Vulgaris Fruit: Determination of Phenolic Compounds in Extracts Obtained by Supercritical CO2 and Soxhlet Methods Using HPLC.

Recently, research studies on nutraceutically important polyphenolic substances have attracted intensive attention. Berberis vulgaris is an important source of polyphenolic compounds and is often used in traditional medicine. In this study, the extraction of rutin and apigenin rich oil from Berberis vulgaris fruits was evaluated by supercritical carbon dioxide (Sc-CO2) extraction method with and without co-solvent. As valuable antioxidants, rutin and apigenin content of extracts were analyzed by HPLC, and their amounts were maximized via parametric optimization. The rutin compound studied in this research has the potential to be a drug against the COVID-19 virus. The operating conditions were considered in the range of 35-70 °C temperatures, 140-240 bar of pressures, 0.35-1.00 mm of mean particle sizes, 3-7 l/min of CO2 flow rates, and 0-8% w/w co-solvent. As a result of Sc-CO2 extractions, the amounts of rutin and apigenin were found as 173 ± 14.97 µg/g and 2.91 ± 0.11 µg/g, respectively, with the 8% (w/w) co-solvent addition. The amounts of rutin and apigenin obtained by Soxhlet extractions were found as 208.81 ± 8.48 µg/g and 6.55 ± 0.21 µg/g, respectively. When the Sc-CO2 method was compared with the Soxhlet method, it was seen that the fast and eco-friendly Sc-CO2 method was an ideal extraction method by providing 76.89% rutin and 44.53% apigenin recoveries. As a result of this study, the maximum extraction conditions for rutin and apigenin were obtained as 160 bar, 40 °C, 0.35 mm particle size, 3 l/min CO2, 8% w/w co-solvent ratio, and 120 min extraction period. Supplementary Information: The online version contains supplementary material available at 10.1007/s12161-021-02136-8.

l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells.

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutin/l-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.

Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies.

In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (1-4) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC50) and SARS-CoV-2 inhibitory concentrations (IC50). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1ß, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2, gallic acid 3, and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC50 values of 31 µg/mL, 108 µg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.

Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19).

The Coronavirus Disease 2019 (COVID-19) has been declared as a global pandemic, but specific medicines and vaccines are still being developed. In China, interventional therapies with traditional Chinese medicine for COVID-19 have achieved significant clinical efficacies, but the underlying pharmacological mechanisms are still unclear. This article reviewed the etiology of COVID-19 and clinical efficacy. Both network pharmacological study and literature search were used to demonstrate the possible action mechanisms of Chinese medicines in treating COVID-19. We found that Chinese medicines played the role of antivirus, anti-inflammation and immunoregulation, and target organs protection in the management of COVID-19 by multiple components acting on multiple targets at multiple pathways. AEC2 and 3CL protein could be the direct targets for inhibiting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Quercetin, kaempferol, luteolin, isorhamnetin, baicalein, naringenin, and wogonin could be the main active ingredients of Chinese medicines for the management of COVID-19 by targeting on AEC2 and 3CL protein and inhibiting inflammatory mediators, regulating immunity, and eliminating free radicals through COX-2, CASP3, IL-6, MAPK1, MAPK14, MAPK8, and REAL in the signaling pathways of IL-17, arachidonic acid, HIF-1, NF-κB, Ras, and TNF. This study may provide meaningful and useful information on further research to investigate the action mechanisms of Chinese medicines against SARS-CoV-2 and also provide a basis for sharing the "China scheme" for COVID-19 treatment.

Antiviral Activity of Metabolites from Peruvian Plants against SARS-CoV-2: An In Silico Approach.

(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. (2) Methods: We applied in silico technics, such as virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA estimation. (3) Results: Rutin, a compound present in Peruvian native plants, showed affinity against three targets of SARS-CoV-2. The molecular dynamics simulation demonstrated the high stability of receptor-ligand systems during the time of the simulation. Our results showed that the Mpro-Rutin system exhibited higher binding free energy than PLpro-Rutin and N-Rutin systems through MM/GBSA analysis. (4) Conclusions: Our study provides insight on natural metabolites from Peruvian plants with therapeutical potential. We found Rutin as a potential candidate with multiple pharmacological properties against SARS-CoV-2.

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.

Interaction of small molecules with the SARS-CoV-2 papain-like protease: In silico studies and in vitro validation of protease activity inhibition using an enzymatic inhibition assay.

The SARS-CoV-2 virus is causing COVID-19, an ongoing pandemic, with extraordinary global health, social, and political implications. Currently, extensive research and development efforts are aimed at producing a safe and effective vaccine. In the interim, small molecules are being widely investigated for antiviral effects. With respect to viral replication, the papain-like (PLpro) and main proteases (Mpro), are critical for processing viral replicase polypeptides. Further, the PLpro possesses deubiquitinating activity affecting key signalling pathways, including inhibition of interferon and innate immune antagonism. Therefore, inhibition of PLpro activity with small molecules is an important research direction. Our aim was to focus on identification of potential inhibitors of the protease activity of SARS-CoV-2 PLpro. We investigated 300 small compounds derived predominantly from our OliveNet™ library (222 phenolics) and supplemented with synthetic and dietary compounds with reported antiviral activities. An initial docking screen, using the potent and selective noncovalent PLpro inhibitor, GRL-0617 as a control, enabled a selection of 30 compounds for further analyses. From further in silico analyses, including docking to scenes derived from a publicly available molecular dynamics simulation trajectory (100 µs PDB 6WX4; DESRES-ANTON-11441075), we identified lead compounds for further in vitro evaluation using an enzymatic inhibition assay measuring SARS-CoV-2 PLpro protease activity. Our findings indicate that hypericin possessed inhibition activity, and both rutin and cyanidin-3-O-glucoside resulted in a concentration-dependent inhibition of the PLpro, with activity in the micromolar range. Overall, hypericin, rutin, and cyanidin-3-O-glucoside can be considered lead compounds requiring further characterisation for potential antiviral effects in appropriate model systems.

Dual inhibition of SARS-CoV-2 spike and main protease through a repurposed drug, rutin.

The global health emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to alarming numbers of fatalities across the world. So far the researchers worldwide have not been able to discover a breakthrough in the form of a potent drug or an effective vaccine. Therefore, it is imperative to discover drugs to curb the ongoing menace. In silico approaches using FDA approved drugs can expedite the drug discovery process by providing leads that can be pursued. In this report, two drug targets, namely the spike protein and main protease, belonging to structural and non-structural class of proteins respectively, were utilized to carry out drug repurposing based screening. The exposed nature of the spike protein on the viral surface along with its instrumental role in host infection and the involvement of main protease in processing of polyproteins along with no human homologue make these proteins attractive drug targets. Interestingly, the screening identified a common high efficiency binding molecule named rutin. Further, molecular dynamics simulations in explicit solvent affirmed the stable and sturdy binding of rutin with these proteins. The decreased Rg value (4 nm for spike-rutin and 2.23 nm for main protease-rutin) and stagnant SASA analysis (485 nm/S2/N in spike-rutin and 152 nm/S2/N in main protease-rutin) for protein surface and its orientation in the exposed and buried regions suggests a strong binding interaction of the drug. Further, cluster analysis and secondary structure analysis of complex trajectories validated the conformational changes due to binding of rutin.

Breeding Buckwheat for Increased Levels of Rutin, Quercetin and Other Bioactive Compounds with Potential Antiviral Effects.

Common buckwheat (Fagopyrum esculentum Moench) and Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) are sources of many bioactive compounds, such as rutin, quercetin, emodin, fagopyrin and other (poly)phenolics. In damaged or milled grain under wet conditions, most of the rutin in common and Tartary buckwheat is degraded to quercetin by rutin-degrading enzymes (e.g., rutinosidase). From Tartary buckwheat varieties with low rutinosidase activity it is possible to prepare foods with high levels of rutin, with the preserved initial levels in the grain. The quercetin from rutin degradation in Tartary buckwheat grain is responsible in part for inhibition of α-glucosidase in the intestine, which helps to maintain normal glucose levels in the blood. Rutin and emodin have the potential for antiviral effects. Grain embryos are rich in rutin, so breeding buckwheat with the aim of producing larger embryos may be a promising strategy to increase the levels of rutin in common and Tartary buckwheat grain, and hence to improve its nutritional value.

Discovery of Potential Flavonoid Inhibitors Against COVID-19 3CL Proteinase Based on Virtual Screening Strategy.

The outbreak of 2019 novel coronavirus (COVID-19) has caused serious threat to public health. Discovery of new anti-COVID-19 drugs is urgently needed. Fortunately, the crystal structure of COVID-19 3CL proteinase was recently resolved. The proteinase has been identified as a promising target for drug discovery in this crisis. Here, a dataset including 2030 natural compounds was screened and refined based on the machine learning and molecular docking. The performance of six machine learning (ML) methods of predicting active coronavirus inhibitors had achieved satisfactory accuracy, especially, the AUC (Area Under ROC Curve) scores with fivefold cross-validation of Logistic Regression (LR) reached up to 0.976. Comprehensive ML prediction and molecular docking results accounted for the compound Rutin, which was approved by NMPA (National Medical Products Administration), exhibited the best AUC and the most promising binding affinity compared to other compounds. Therefore, Rutin might be a promising agent in anti-COVID-19 drugs development.