ABSTRACT
This study aimed to establish a validated HPLC-UV analytical method for the determination of gallic acid, catechin, scopoletin, and umckalin in phytoformulations containing P. sidoides. Also, to assess the anti-SARS-CoV-2 effect of P. sidoides and these biomolecules in vitro. An HPLC-UV method was developed and verified by testing the commercial forms, Kalobin® and Umca®. It revealed low detectable scopoletin and high umckalin levels. Pelargonium sidoides exhibited a significant reduction of SARS-CoV-2-induced cytopathic effect in Vero E6 cells (IC50 13.79 µg/mL and selectivity index, SI 6.3), whereas scopoletin showed a remarkable anti-SARS-CoV-2 activity with better selectivity (IC50 17.79 µg/mL and SI 14.22). An in-silico prediction of the drugability indicated that the studied biomolecules are under the acceptable norms of Lipinski's rule, water-soluble, and showed high GIT absorption and bioavailability. Docking study towards the essential molecular targets for viral replication and entry of SARS-CoV-2 indicated good binding affinity of scopoletin (-6.4 Kcal/mol) towards the interface region between the SARS-CoV-2 spike protein RBD and the ACE2 surface receptor indicating the probability of interference with the viral entry to the human cells and showed H-bonding with His-41 in the active site of the main protease which may explain its high antiviral activity.
ABSTRACT
Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.