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Proceeding our prior studies of SARS-CoV-2, the inhibitory potential against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has been investigated for a collection of 3009 clinical and FDA-approved drugs. A multi-phase in silico approach has been employed in this study. Initially, a molecular fingerprint experiment of Remdesivir (RTP), the co-crystallized ligand of the examined protein, revealed the most similar 150 compounds. Among them, 30 compounds were selected after a structure similarity experiment. Subsequently, the most similar 30 compounds were docked against SARS-CoV-2 RNA-dependent RNA polymerase (PDB ID: 7BV2). Aloin 359, Baicalin 456, Cefadroxil 1273, Sophoricoside 1459, Hyperoside 2109, and Vitexin 2286 exhibited the most precise binding modes, as well as the best binding energies. To confirm the obtained results, MD simulations experiments have been conducted for Hyperoside 2109, the natural flavonoid glycoside that exhibited the best docking scores, against RdRp (PDB ID: 7BV2) for 100 ns. The achieved results authenticated the correct binding of 2109, showing low energy and optimum dynamics. Our team presents these outcomes for scientists all over the world to advance in vitro and in vivo examinations against COVID-19 for the promising compounds.

The cardiotoxic adverse effect of doxorubicin (DOX) is the major factor limiting its use. Recently, mesenchymal stem cells (MSCs) have been implicated in the preclinical studies of treatment of DOX-induced cardiotoxicity. The question is MSCs pretreated with platelet-rich plasma (PRP) have a better influence on DOX-induced cardiotoxicity compared to the influence of MSCs alone. Twenty-four Wistar rats were categorized into control, DOX-treated, MSC-treated, and PRP/MSC-treated groups. DOX was injected for two consecutive weeks. Light microscopic, biochemical markers (interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and creatine kinase-MB (CK-MB)), immunohistochemical (Bax, Bcl2, vascular endothelial growth factor (VEGF), and cardiac troponin-I (CT-I)), and oxidative/antioxidative markers (malondialdehyde (MDA)/superoxide dismutase (SOD)) were measured. Degenerative cardiac changes were detected in the DOX-treated group with complete loss of the architecture and coagulative necrosis. These changes were accompanied with the elevation of the serum level of CK-MB and loss of CT-I immunoreactivity. The major factors in the DOX-induced cardiotoxicity were the oxidative stress (elevated MDA/decreased SOD), inflammation (elevated TNF-α/decreased IL-10), and cardiac apoptosis (lower Bcl2, higher Bax, and lower Bcl2/Bax ratio). MSCs and PRP/MSCs attenuate DOX-induced cardiotoxicity. Better attenuation was observed in the PRP/MSC-treated group. PRP/MSC combination reduced greatly the MDA and TNF-α and increased IL-10, Bcl2/Bax ratio, and VEGF. PRP had no significant influence over the Bcl2, Bax, and SOD. In conclusion, DOX in its toxic dose induced myocardial injury. This destructive effect is related to oxidative stress, inflammation, and cardiac apoptosis. PRP/MSC possesses a better attenuation over the DOX-induced toxicity compared to MSC alone.