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Asarum heterotropoides var. mandshuricum F. Maekawa (Aristolochiaceae), well-known as "Marchurian Wildginger", shows many bioactivities that contribute to its therapeutic effects against a wide range of diseases. In this study, phytochemical investigation of A. hetertotropoides var. mandshuricum root extract led to the isolation of one previously undescribed amide (asamide A) with a rare five-membered-ring acetonide group in natural sources and one new amide mixture (asamide B/C) together with fifteen known alkaloids and one known amide mixture. Structural elucidation of the new alkaloids was carried out based on conventional NMR spectroscopy, HRESI-MS, and ECD calculation. To the best of our knowledge, this is the first report on the isolation of asaroidoxazine B from A. heterotropoides var. mandshuricum and compounds N -feruloyl tyramine, trans - N -feruloyl octopamine, and N - trans - p -coumaroyltopamin from the genus Asarum. The isolated alkaloids were examined for their inhibitory effects on PDB6LU7 protein of SARS-CoV-2 by molecular docking. Accordingly, the isolated aristolactams, especially aristolactam glycosides were found to be promising agents for the research and development of the new anti-SARS-CoV-2 drugs. [Display omitted] • Sixteen alkaloids and two amide mixtures were isolated from A. heterotropoides root. • Among them, one new amide and one new amide mixture were discovered. • Their structures were identified by spectroscopic data and ECD calculation. • The new amide contained a rare five-membered-ring acetonide in natural sources. • Aristolactams showed promising inhibitory effects against PDB6LU7 SARS-CoV-2 protein. [ABSTRACT FROM AUTHOR]

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, remarkable advances have been made in vaccine development to reduce mortality. However, therapeutic interventions for COVID-19 are comparatively limited despite these intensive efforts. Furthermore, the rapid mutation capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a characteristic of its RNA structure, has led to the emergence of multiple variants, necessitating a shift from a predominantly vaccine-centric approach to one that encompasses therapeutic strategies. 6′-Hydroxy justicidin B (6′-HJB), an arylnaphthalene lignan isolated from Justicia procumbens , a traditional Chinese medicine, is known for its antiviral properties. The aim of the present study was to assess the effectiveness and safety of 6′-HJB against SARS-CoV-2 in order to determine its potential as a therapeutic agent against COVID-19. The efficacy of 6′-HJB was evaluated both in vitro using Vero and Calu-3 cell lines and in vivo using ferrets. The safety assessment included toxicokinetics, safety pharmacology, and Good Laboratory Practice (GLP)-compliant toxicity evaluations following single- and repeated-dose toxicity studies in dogs. The anti-SARS-CoV-2 efficacy of 6′-HJB was evaluated through dose-response curve (DRC) analysis using immunofluorescence; 6′-HJB demonstrated superior inhibition of SARS-CoV-2 growth and lower cytotoxicity than remdesivir. In SARS-CoV-2-infected ferret, 6′-HJB showed efficacy comparable to that of the positive control, Truvada. Further GLP toxicity studies corroborated the safety profile of 6′-HJB. Single-dose and 4-week repeated oral toxicity studies in Beagle dogs demonstrated minimal harmful effects at the highest dosages. The lethal dose of 6′-HJB exceeded 2,000 mg kg-1 in Beagle dogs. Toxicokinetic and GLP safety pharmacology studies demonstrated no adverse effects of 6′-HJB on metabolic processes, respiratory or central nervous systems, or cardiac functions. This research highlights both the antiviral efficacy and safety profile of 6′-HJB, underscoring its potential as a novel COVID-19 treatment option. The potential of 6′-HJB was demonstrated using modern scientific methodologies and standards. [Display omitted] [ABSTRACT FROM AUTHOR]