In the present study, the toxicity of gold nanoparticles (Au NPs) was evaluated on various trophic organisms. Bacteria, algae, cell line, and mice were used as models representing different trophic levels. Two different sizes (CIT30 and CIT40) and surface-capped (CIT30-polyvinyl pyrrolidone (PVP)-capped) Au NPs were selected. CIT30 Au NP aggregated more rapidly than CIT40 Au NP, while an additional capping of PVP (CIT30-PVP capped Au NP) was found to enhance its stability in sterile lake water medium. Interestingly, all the forms of NPs evaluated were stable in the cell culture medium during the exposure period. Size- and dose-dependent cytotoxicities were observed in both bacteria and algae, with a strong dependence on reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) release. CIT30-PVP capped Au NP showed a significant decrease in toxicity compared to CIT30 Au NP in bacteria and algae. In the SiHa cell line, dose- and exposure-dependent decline in cell viability were noted for all three types of Au NPs. In mice, the induction of DNA damage was size and dose dependent, and surface functionalization with PVP reduced the toxic effects of CIT30 Au NP. The exposure to CIT30, CIT40, and CIT30-PVP capped Au NPs caused an alteration of the oxidative stress-related endpoints in mice hepatocytes. The toxic effects of the gold nanoparticles were found to vary in diverse test systems, accentuating the importance of size and surface functionalization at different trophic levels.
Background
This world is currently witnessing a pandemic outbreak of 'COVID-19' caused by a positive-strand RNA virus 'SARS-CoV-2’. Millions have succumbed globally to the disease, and the numbers are increasing day by day. The viral genome enters into the human host through interaction between the spike protein (S) and host angiotensin-converting enzyme-2 (ACE2) proteins. S is the common target for most recently rolled-out vaccines across regions. A recent surge in single/multiple mutations in S region is of great concern as it may escape vaccine induced immunity. So far, the treatment regime with repurposed drugs has not been too successful.
Hypothesis
Natural compounds are capable of targeting mutated spike protein by binding to its active site and destabilizing the spike-host ACE2 interaction.
Materials and methods
A hypothetical mutated spike protein was constructed by incorporating 12 different mutations from twelve geographical locations simultaneously into the receptor-binding domain (RBD) and docked with ACE2 and seven phytochemicals namely allicin, capsaicin, cinnamaldehyde, curcumin, gingerol, piperine and zingeberene. Molecular Dynamic (MD) simulation and Principal Component Analysis (PCA) were finally used for validation of the docking results.
Result
The docking results showed that curcumin and piperine were most potent to bind ACE2, mutated spike, and mutated spike-ACE2 complex, thereby restricting viral entry. ADME analysis also proved their drug candidature. The docking complexes were found to be stable by MD simulation.
Conclusion
This result provides a significant insight about the phytochemicals' role, namely curcumin and piperine, as the potential therapeutic entities against mutated spike protein of SARS-CoV-2.
BackgroundNatural compounds can be alternative sources for finding new lead anti-cancer molecules. Marine algae have been a traditional source for bioactive compounds. Enteromorpha intestinalis and Rhizoclonium riparium are two well distributed saline/brackish water algae from Sundarbans. There’s no previous report of these two for their anti-proliferative activities.MethodsCytotoxicity of the algal methanolic extracts (AMEs) on HeLa cells were assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) reduction assay. Morphological examinations were done by Haematoxylin, Hoechst 33258 and Acridine orange staining. DNA fragmentation was checked. Gene expressions of Cysteine aspartate protease (Caspase) 3, Tumor protein (TP) 53, Bcl-2 associated protein X (Bax) were studied by Reverse transcription- polymerase chain reaction (RT-PCR) keeping Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as internal control. Protein expressions were studied for Caspase 3, phospho-p53, Bax, Microtubule associated proteins-1/ light chain B (MAP1/LC3B) by western blot.ResultsThe AMEs were found to be cytotoxic with Inhibitory concentration 50 (IC50) values 309.048 ± 3.083 μg/ml and 506.081 ± 3.714 μg/ml for E. intestinalis and R. riparium extracts respectively. Treated cells became round with blebbings with condensed nuclei. Acidic lysosomal vacuoles formation occurred in treated cells. Expression of apoptotic genes in both mRNA and protein level was lowered. Expression of LC3B-II suggested occurrence of autophagy in treated cells.ConclusionsThese two algae can be potent candidates for isolating new lead anticancer molecules. So they need further characterization at both molecular and structural levels.
The reaction of 2-hydroxybenzoylhydrazine (Hbh) separately with equimolar amounts of [VO(aa)] and [VO(ba)] in CHCl afforded the complexes [VO(HL)] (1) and [VO(HL)] (2) respectively in good to excellent yield ((HL) and (HL) represent respectively the dianionic form of 2-hydroxybenzoylhydrazones of acetylacetone (HL) and benzoylacetone (HL) (general abbreviation HL)). From X-ray structure analysis, the V-O-V angle was found to be ∼115° and 180° in 1 and 2 respectively. Upon one-electron reduction selectively at one V centre at an appropriate potential, each of 1 and 2 generated mixed-valence [(HL)VO-(μ-O)-OV(HL)] species 1A and 2A respectively, which showed valence delocalization at room temperature and localization at 77 K, and the V-O-V bond angles were calculated to be 177.5° and 180° respectively. The intercalative mode of binding of the two complexes 1 and 2 with CT DNA has been suggested by UV-visible spectroscopy (K = 7.31 × 10 M and 8.71 × 10 M respectively for 1 and 2), fluorescence spectroscopy (K = 6.85 × 10 M and 8.53 × 10 M respectively for 1 and 2) and circular dichroism spectroscopy. Such intercalative mode of binding of these two complexes with CT DNA and HPV DNA has also been confirmed by molecular docking study. Both complexes 1 and 2 exhibited promising anti-cancer activity against SiHa cervical cancer cells with IC values of 28 ± 0.5 μM and 25 ± 0.5 μM respectively for 24 h which is significantly better than that of widely used cisplatin (with IC value of 63.5 μM). Nuclear staining experiments reveal that these complexes kill the SiHa cells through apoptotic mode. It is interesting to note that these two complexes are non-toxic to normal T293 cell line. Complex 2 showed higher DNA binding ability with CT DNA and HPV DNA as well as better anti-cancer properties towards SiHa cervical cancer cells in comparison to complex 1, a fact which can be explained by considering the lower energy of LUMO (which favours electron transition from DNA to the metal complex) and also the higher surface area of complex 2 in comparison to complex 1 due to the presence of one extra electron-withdrawing phenyl group in the former.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.