Patent Blue V (PBV) is a water-soluble synthetic dyestuff that is used as a coloring agent in the food industry and for medical imaging in health monitoring. The aim of this study was to investigate the in vitro clastogenic, aneugenic and cytotoxic effects of PBV in human peripheral lymphocytes using micronucleus assay, comet assay, as well as plasmid DNA interaction and bacterial AMES tests. In addition to in vitro tests, the affinity of PBV against DNA was determined by molecular docking analysis in silico. PBV produced significant MN formation only at high doses and longer treatment time, however, it did not significantly affect the nuclear division index (NDI). Furthermore, PBV was unable to cause DNA single-strand breaks and significant oxidative damage on the pBR322 plasmid DNA and it didn’t reverse the harmful effects caused by the clastogenic treatment of UV + H₂O₂ on plasmid DNA. In the Ames test, no significant increase was detected in the number of revertant colonies of mutant strains, TA98 and TA100, following PBV treatment. No significant molecular interaction between B-DNA and PBV occured in molecular docking simulations. In conclusion, PBV had no significant genotoxic and cytotoxic effects in this study. However, considering that the information intensity related to the genotoxic effects of PBV in the literature is still insufficient, reports of further studies with different genotoxicity endpoints will be needed to elucidate the exact genotoxic feature.

Coronavirus Disease 2019 (COVID-19) has infected more than thirty five million people worldwide and caused nearly 1 million deaths as of October 2020. The microorganism causing COVID-19 was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV). The aim of this study was to investigate the interactions of twenty-three phytochemicals belonging to different flavonoid subgroups with the receptor binding domain (RBD) of the spike glycoprotein of 2019-nCoV, and cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B and L (CatB/L)]. The compounds interacted more strongly with CatB and CatL than with the other proteins. Van der Waals and hydrogen bonds played an important role in the receptor-ligand interactions. As a result of RBCI (relative binding capacity index) analysis conducted to rank flavonoids in terms of their interactions with the target proteins, (-)-epicatechin gallate interacted strongly with all the proteins studied. The results obtained from molecular dynamics and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) methods also supported this data. According to Lipinski's rule of five, (-)-epicatechin gallate showed drug-likeness properties. Although this molecule is not capable of crossing the blood-brain barrier (BBB), it was concluded that (-)-epicatechin gallate can be evaluated as a candidate molecule in drug development studies against 2019-nCoV since it was not the substrate of P-gp (P-glycoprotein), did not inhibit any of the cytochrome Ps, and did not show AMES toxicity or hepatotoxicity on eukaryotic cells.

As of June 2020, the coronavirus disease 19 (COVID-19) caused by the 2019 new type coronavirus (2019-nCoV) infected more than 7,000,000 people worldwide and caused the death of more than 400,000 people. The aim of this study was to investigate the molecular interactions between monoterpenoids and spike protein of 2019-nCoV together with the cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B (CatB), and cathepsin L (CatL)]. As a result of the relative binding capacity index (RBCI) analysis, carvone was found to be the most effective molecule against all targets when binding energy and predicted (theoretical) IC50 data were evaluated together. It was found to exhibit drug-likeness property according to the Lipinski’s rule-of-five. Carvone has also been determined to be able to cross the blood-brain barrier (BBB) effectively, not a substrate for P-glycoprotein (P-gp), not to inhibit any of the cytochrome P molecules, and to have no toxic effects even on liver cells. In addition, the LD50 dose of carvone in rats was 1.707 mol/kg. Due to its interaction profile with target proteins and excellent pharmacokinetic properties, it has been concluded that carvone can be considered as an alternative agent in drug development studies against 2019-nCoV.

Covid-19 is a viral disease caused by the virus SARS-CoV-2 that spread worldwide and caused more than 4.3 million deaths. Moreover, SARS-CoV-2 still continues to evolve, and specifically the E484K, N501Y, and South Africa triple (K417N + E484K + N501Y) spike protein mutants remain as the ‘escape’ phenotypes. The aim of this study was to compare the interaction between the receptor binding domain (RBD) of the E484K, N501Y and South Africa triple spike variants and ACE2 with the interaction between wild-type spike RBD-ACE2 and to show whether the obtained binding affinities and conformations corraborate clinical findings. The structures of the RBDs of the E484K, N501Y and South Africa triple variants were generated with DS Studio v16 and energetically minimized using the CHARMM22 force field. Protein-protein dockings were performed in the HADDOCK server and the obtained wild-type and mutant spike-ACE2 complexes were submitted to 200-ns molecular dynamics simulations with subsequent free energy calculations using GROMACS. Based on docking binding affinities and free energy calculations the E484K, N501Y and triple mutant variants were found to interact stronger with the ACE2 than the wild-type spike. Interestingly, molecular dynamics and MM-PBSA results showed that E484K and spike triple mutant complexes were more stable than the N501Y one. Moreover, the E484K and South Africa triple mutants triggered greater conformational changes in the spike glycoprotein than N501Y. The E484K variant alone, or the combination of K417N + E484K + N501Y mutations induce significant conformational transitions in the spike glycoprotein, while increasing the spike-ACE2 binding affinity. Communicated by Ramaswamy H. Sarma

The aim of this study was to investigate the chemical composition, antioxidant and enzyme inhibitory activities of methanol (MeOH) extracts from Onosma bourgaei (Boiss.) and O. trachytricha (Boiss.). In addition, the interactions between phytochemicals found in extracts in high amounts and the target enzymes in question were revealed at the molecular scale by performing in silico molecular docking simulations. While the total amount of flavonoid compounds was higher in O. bourgaei, O. trachytricha was richer in phenolics. Chromatographic analysis showed that the major compounds of the extracts were luteolin 7-glucoside, apigenin 7-glucoside and rosmarinic acid. With the exception of the ferrous ion chelating assay, O. trachytricha exhibited higher antioxidant activity than O. bourgaei. O. bourgaei exhibited also slightly higher activity on digestive enzymes. The inhibitory activities of the Onosma species on tyrosinase were almost equal. In addition, the inhibitory activities of the extracts on acetylcholinesterase (AChE) were stronger than the activity on butyrylcholinesterase (BChE). Molecular docking simulations revealed that luteolin 7-glucoside and apigenin 7-glucoside have particularly strong binding affinities against ChEs, tyrosinase, α-amylase and α-glucosidase when compared with co-crystallized inhibitors. Therefore, it was concluded that the compounds in question could act as effective inhibitors on cholinesterases, tyrosinase and digestive enzymes.