The attachment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike to angiotensin-converting enzyme 2 (ACE-2) leads the cell fusion process, so spike blockade may be a promising therapy combating COVID-19. Bee pollen bioflavonoids with intrinsic bioactivities are of outmost importance to block SARS-CoV-2-ACE-2 interaction. Herein, we conducted a molecular docking assessment through natural phenolics/non-phenolics of pollen to investigate their affinity against SARS-CoV-2 spike. Finally, kaempferol 3-neohesperidoside 7-O-rhamnoside (compound a), quercetin 7-rhamnoside (compound b), delphinidin-3-O-(6-p-coumaroyl) glucoside (compound c), and luteolin-7-O-6″-malonylglucoside (compound d) showed the lowest binding affinity of −8.1, −7.7, −7.3 and −6.7 kcal/mol. The docking procedure was validated using protein-protein interactions between ACE-2 and SARS-CoV-2 RBD via HADDOCK webserver. MD simulations were fulfilled to investigate different ligands’ effects on protein movements. Collectively, compound a may possess the potency to disturb the binding of SARS-CoV-2 spike-ACE-2, which can be on the call for further in vitro and in vivo study to investigate its antiviral potential against SARS-CoV-2. Graphical Abstract

In this study, phytochemicals extracted from three different Achillea genera were identified and analyzed to be screened for their interactions with the SARS-CoV-2 main protease. In particular, the antiviral potential of these natural products against the SARS-CoV-2 main protease was investigated, as was their effectiveness against the SARS-CoV-1 main protease as a standard (due to its high similarity with SARS-CoV-2). These enzymes play key roles in the proliferation of viral strains in the human cytological domain. GC-MS analysis was used to identify the essential oils of the Achillea species. Chemi-informatics tools, such as AutoDock 4.2.6, SwissADME, ProTox-II, and LigPlot, were used to investigate the action of the pharmacoactive compounds against the main proteases of SARS-CoV-1 and SARS-CoV-2. Based on the binding energies of kessanyl acetate, chavibetol (m-eugenol), farnesol, and 7-epi-β-eudesmol were localized at the active site of the coronaviruses. Furthermore, these molecules, through hydrogen bonding with the amino acid residues of the active sites of viral proteins, were found to block the progression of SARS-CoV-2. Screening and computer analysis provided us with the opportunity to consider these molecules for further preclinical studies. Furthermore, considering their low toxicity, the data may pave the way for new in vitro and in vivo research on these natural inhibitors of the main SARS-CoV-2 protease.

Catalytic C-H activation is a powerful method for organic synthesis. In recent years, scientists have made great progress by developing transitional metals for catalyzing C-H functionalization reaction. In this review, we summarized and highlighted recent progress in C-H activation with copper, cobalt, iron, manganese, and nickel as catalysts.