Evaluation of nanoplastics toxicity to the human placenta in systems.

Following the discovery of plastics in the human placenta, this study evaluated the toxicity of ten different nanoplastics (NPs) in the human placenta. Since the placenta performs metabolic and excretion functions by the enzymatic system, the NPs were docked on these human enzymes including soluble epoxide hydrolase, uracil phosphoribosyltransferase, beta 1,3-glucuronyltransferase I, sulfotransferase, N-acetyltransferase 2, and cytochrome P450 1A1at their active sites with toxicity (binding affinity) determined and compared to control compounds. Density functional theory analysis were conducted on the NPs to identify their global reactivity descriptors and Artificial Neural Networks to predict toxicity based on reactivity descriptors. Polycarbonate (PC), polyethylene terephthalate (PET) and polystyrene (PS) showed the highest toxicity to all enzymes and thus the most toxic polymers due to the presence of an electron-withdrawing group in their aromatic rings, which demonstrated an improved recognition of the enzyme active site by pi- and alkyl interactions. A 210-6 fractional factorial design approach was used in conjunction with a fixed effects model to assess the primary and secondary effects of NPs in a composite system on binding affinity to the placental enzymes. The simulation results suggest that NPs mixture may pose significant risks to the placenta through inhibition of its key enzymes.

Blocking the interactions between human ACE2 and coronavirus spike glycoprotein by selected drugs: a computational perspective.

The coronavirus disease of 2019 (COVID-19) has become a global pandemic with rapid rate of transmission and fatalities worldwide. Scientists have been investigating a host of drugs that may be rechanneled to fight this malaise. Thus, in this current computational study we carried out molecular docking experiments to assess the bridging potentials of some commercial drugs such as chloroquine, hydroxychloroquine, lopinavir, ritonavir, nafamostat, camostat, famotidine, umifenovir, nitazoxanide, ivermectin, and fluvoxamine at the interface between human ACE2 and the coronavirus spike glycoprotein complex. This is aimed at ascertaining the ability of these drugs to bridge and prevent the complexing of these two proteins. The crystal structure of human ACE2 and the coronavirus spike glycoprotein complex was retrieved from protein database, while the selected drugs were retrieved from PubChem data base. The proteins and drugs were prepared for docking using Cresset Flare software. The docking was completed via AutoDock Vina module in Python Prescription software. The best hit drugs with each receptor were selected and their molecular interactions were analyzed using BIOVIA's Discovery Studio 2020. The best hit compounds on the human ACE2 were the lopinavir (-10.1 kcal/mol), ritonavir (-8.9 kcal/mol), and nafamostat (-8.7 kcal/mol). Ivermectin, nafamostat, and camostat with binding energy values -9.0 kcal/mol, -7.8 kcal/mol, and -7.4 kcal/mol respectively were the hit drugs on the coronavirus spike glycoprotein. Nafamostat showed a dual bridging potential against ACE2 and spike glycoprotein, and could therefore be a promising lead compound in the prevention and control of this disease.

In silico identification of compounds from Nigella sativa seed oil as potential inhibitors of SARS-CoV-2 targets.

BACKGROUND: The growing number of cases, severity and fatality of the COVID-19 pandemic, coupled with the fact that no cure has been found has made infected individuals especially in Africa, to resort to the consumption of different natural products to alleviate their condition. One of such plant materials that have been consumed to remedy the severity of this viral infection is the oil of Nigella sativa seed commonly called black seed oil. In this study, we extracted and characterized the oil from this seed using gas chromatography coupled to a mass selective detector to identify the component phytochemicals. Site-directed multiligand docking of the identified compounds was performed on SARS-CoV-2 molecular targets- Replicase polyprotein 1a, RNA binding protein of NSP9, ADP ribose phosphatase of NSP3, 3-chymotrypsin-like protease 3CLpro, and RNA-dependent RNA polymerase RDRP, and ACE2-angiotensin-converting enzyme from the Homo sapiens. RESULTS: The binding affinity of caryophyllene oxide was the highest on 3CLpro (- 6.0 kcal/mol), NSP3 (- 6.3 kcal/mol), NSP9 (- 6.3 kcal/mol), and RDRP (- 6.9 kcal/mol) targets, while α-bergamotene gave the best binding affinity on RPIA (5.7 kcal/mol) target. The binding affinity of ß-bisabolene on the ACE2 target (- 8.0 kcal/mol) was almost the same as Remdesivir (- 8.1 kcal/mol). The ADMET properties of these three phytochemicals showed that they are good drug leads for these SARS-CoV-2 receptors. CONCLUSION: The findings from this study strongly indicate that the reported recovery from COVID-19 infection claimed by patients who consumed black seed oil could be linked to the presence of caryophyllene oxide, α-bergamotene, and ß-bisabolene in this natural product.