In Silico Studies on Zinc Oxide Based Nanostructured Oil Carriers with Seed Extracts of Nigella sativa and Pimpinella anisum as Potential Inhibitors of 3CL Protease of SARS-CoV-2

Abstract

Coming into the second year of the pandemic, the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants continue to be a serious health hazard globally. A surge in the omicron wave, despite the discovery of the vaccines, has shifted the attention of research towards the discovery and use of bioactive compounds, being potential inhibitors of the viral structural proteins. The present study aimed at the green synthesis of zinc oxide (ZnO) nanoparticles with seed extracts of Nigella sativa and Pimpinella anisum—loaded nanostructured oil carriers (NLC)—using a mixture of olive and black seed essential oils. The synthesized ZnO NLC were extensively characterized. In addition, the constituent compounds in ZnO NLC were investigated as a potential inhibitor for the SARS-CoV-2 main protease (3CLpro or Mpro) where 27 bioactive constituents, along with ZnO in the nanostructure, were subjected to molecular docking studies. The resultant high-score compounds were further validated by molecular dynamics simulation. The study optimized the compounds dithymoquinone, δ-hederin, oleuropein, and zinc oxide with high docking energy scores (ranging from −7.9 to −9.9 kcal/mol). The RMSD and RMSF data that ensued also mirrored these results for the stability of proteins and ligands. RMSD and RMSF data showed no conformational change in the protein during the MD simulation. Histograms of every simulation trajectory explained the ligand properties and ligand–protein contacts. Nevertheless, further experimental investigations and validation of the selected candidates are imperative to take forward the applicability of the nanostructure as a potent inhibitor of COVID-19 (Coronavirus Disease 2019) for clinical trials.

Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles

“…The overall RMSF values for the protein alone, as well as when it interacted with ligands, were in the range of 3.6 Å to 4.8 Å, with the exception of Zinc Oxide. These results are fairly similar to those obtained by Hendi and others [ 22 ].…”

“…The final ligand, meropenem, presented three hydrogen bonds with the residues LUS 21, GLY 117, and TRP 299. This indicates that these amino acid residues are necessary for target binding and that they exert activity [ 22 ]. A favorable and stable binding position of the compounds within the binding pocket of the target protein is indicated by extremely low energy scores [ 21 , 23 ].…”

“…The protein–ligand interaction diagram, the root-mean-square deviation of the protein–phytocompound complex, the root-mean-square fluctuation of the protein, the interacting amino acid residues with the ligand in each trajectory frame, and the trajectory of various ligand properties were all examined. Ramachandran plot analysis was used to further evaluate the protein’s overall stability [ 22 ].…”

A Multidimensional Review of Pimpinella anisum and Recommendation for Future Research to Face Adverse Climatic Conditions

“…All LCs were found to inhibit the adsorption of viruses to the host cell surface and disable them via induction of iNOS mRNA of cytokines including IL-1β and IL-10. Currently, seed extracts of P. anisum showed significant effects against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) considered a serious health hazard internationally [ 93 ]. Preparation of green synthesis combining zinc oxide nanoparticles, seed extracts of P. anisum and Nigella sativa loaded nanostructured oil carriers (NLC) (composed from black seed and olive essential oils) were extensively characterized (high docking energy scores (ranging from − 7.9 to − 9.9 kcal/mol) and tested against SARS-CoV-2 main protease (3CLpro or Mpro).…”

Improving Dietary Zinc Bioavailability Using New Food Fortification Approaches: A Promising Tool to Boost Immunity in the Light of COVID-19

“…Furthermore, several recent in silico studies have demonstrated by molecular docking analysis that Zn could have a strong affinity and inhibit the main cellular compound targets of SARS-CoV-2, including the angiotensin-converting enzyme 2 (ACE2) receptor (which could be considered the main entry target of the virus), RNA-dependent RNA polymerase (RdRp), and the main protease activities (3-chyomotrypsin-like protease (3CLpro), etc.) used for virus replication [ 47 , 48 , 49 , 50 ]. Interestingly, the results from recent in vitro studies have confirmed the findings from in silico screening and revealed that Zn alone or in conjugation with other compounds (Zn ionophore, drug, etc.)…”