Phytochemical rich Himalayan <i>Rhododendron arboreum</i> petals inhibit SARS-CoV-2 infection <i>in vitro</i>

Phytochemicals with potential to competitively bind to the host receptors or inhibit SARS-CoV-2 replication, may prove to be useful as adjunct therapeutics for COVID-19. We profiled and investigated the phytochemicals of <i>Rhododendron arboreum</i> petals sourced from Himalayan flora, undertook <i>in vitro</i> studies and found it as a promising candidate against SARS-CoV-2. The phytochemicals were reported in various scientific investigations to act against a range of virus <i>in vitro</i> and <i>in vivo,</i> which prompted us to test against SARS-CoV-2. <i>In vitro</i> assays of <i>R. arboreum</i> petals hot aqueous extract confirmed dose dependent reduction in SARS-CoV-2 viral load in infected Vero E6 cells (80% inhibition at 1 mg/ml; IC50 = 173 µg/ml) and phytochemicals profiled were subjected to molecular docking studies against SARS CoV-2 target proteins. The molecules 5-O-Feruloyl-quinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, Epicatechin and Catechin showed promising binding affinity with SARS-CoV-2 Main protease (M^Pro; PDB ID: 6LU7; responsible for viral replication) and Human Angiotensin Converting Enzyme-2 (ACE2; PDB ID: 1R4L; mediate viral entry in the host). Molecular dynamics (MD) simulation of 5-O-Feruloyl-quinic acid, an abundant molecule in the extract complexed with the target proteins showed stable interactions. Taken together, the phytochemical profiling, <i>in silico</i> analysis and <i>in vitro</i> anti-viral assay revealed that the petals extract act upon M^Pro and may be inhibiting SARS-CoV-2 replication. This is the first report highlighting <i>R. arboreum</i> petals as a reservoir of antiviral phytochemicals with potential anti-SARS-CoV-2 activity using an <i>in vitro</i> system. Communicated by Ramaswamy H. Sarma