The natural stilbenoid (-)-hopeaphenol inhibits cellular entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7, and B.1.351 variants

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID- 19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host angiotensin-converting enzyme II (ACE2) receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here, we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (-)-hopeaphenol, a resveratrol tetramer, in addition to vatalbinoside A and vaticanol B, as potent and selective inhibitors of RBD/ACE2 binding and viral entry. For example, (-)-hopeaphenol disrupted RBD/ACE2 binding with a 50% inhibitory concentration (IC50) of 0.11 mM, in contrast to an IC50 of 28.3 mM against the unrelated host ligand/receptor binding pair PD-1/PD-L1 (selectivity index, 257.3). When assessed against the USA-WA1/2020 variant, (-)-hopeaphenol also inhibited entry of a VSVDG-GFP reporter pseudovirus expressing SARS-CoV-2 spike into ACE2-expressing Vero-E6 cells and in vitro replication of infectious virus in cytopathic effect and yield reduction assays (50% effective concentrations [EC50s], 10.2 to 23.4 mM) without cytotoxicity and approaching the activities of the control antiviral remdesivir (EC50s, 1.0 to 7.3 mM). Notably, (-)-hopeaphenol also inhibited two emerging variants of concern, B.1.1.7/Alpha and B.1.351/Beta in both viral and spike-containing pseudovirus assays with similar or improved activities over the USA-WA1/2020 variant. These results identify (-)-hopeaphenol and related stilbenoid analogues as potent and selective inhibitors of viral entry across multiple SARS-CoV-2 variants of concern

Comparative Chemical Analysis of the Essential Oil Constituents in the Bark, Heartwood and Fruits of Cryptocarya massoy (Oken) Kosterm. (Lauraceae) from Papua New Guinea

Exhaustive hydro-distillation of the bark, heartwood and fruits of Cryptocarya massoy (Lauraceae) afforded pale yellow-coloured oils in 0.7, 1.2 and 1.0 % yields, respectively. Detailed chemical evaluation of these distillates using GC/MS revealed the major components in the bark and the heartwood oils to be the C-10 (5,6-dihydro-6-pentyl-2H-pyran-2-one) and C-12 (5,6-dihydro-6-heptyl-2H-pyran-2-one) massoia lactones, while the major fruit oil constituent was benzyl benzoate (68.3 %). The heartwood also contained trace amounts of the C-14 (5,6-dihydro-6-nonyl-2H-pyran-2-one) massoia lactone (1.4 %) and the saturated C-10 derivative d-decalactone (2.5 %)

Volatile Chemical Constituents of Piper aduncum L and Piper gibbilimbum C. DC (Piperaceae) from Papua New Guinea

Exhaustive hydro-distillation of the leaves of Piper aduncum and fruits of Piper gibbilimbum (Piperaceae) afforded colorless and pale orange colored oils in 0.35 and 0.30 % yields, respectively. Detailed chemical analysis by GC/MS indicated the volatile constituents of Piper aduncum to be composed of dill apiole (43.3 %), β-caryophyllene (8.2 %), piperitione (6.7 %) and α-humulene (5.1 %), whilst the oil of P. gibbilimbum is dominated by the gibbilimbols A-D (74.2 %), with the remaining major constituents being the terpenes camphene (13.6 %) and α-pinene (6.5 %)

Volatile chemical constituents of three Ocimum species (Lamiaceae) from Papua New Guinea (SPJNS)

Fresh aerial parts of three species of basil, Ocimum basilicum, O. tacilium and O. canum were subjected to exhaustive hydrodistillation to afford pale yellow coloured oils in 1.0, 0.7 and 0.01 percent yields respectively. Detailed chemical evaluation by GC and GC/MS revealed O. basilicum to be composed of a total of eleven components representing 100 percent of the total oil composition. Neral (36.1 %) and geranial (44.5 %) were found to be the major components. Ocimum tacilium was found to be composed of five components representing 99.8 % of the total oil composition with estragole (96.6 %) being the major component. Five components were observed in O. canum, representing 72.3 percent of the total oil composition with eugenol (35.3 %) and linalool (27.2 %) as the major components. The high citral (neral + geranial) content in O. basilicum suggests that it belong to the citral chemotype while O. tacilium belong to the estragole chemotype and O. canum belong to the eugenol chemotype

New Prenylated Bi- and Tricyclic Phloroglucinol Derivatives from Hypericum papuanum

Five new prenylated tricyclic and three new bicyclic acylphloroglucinol derivs. have been isolated by bioactivity-guided fractionation of the petroleum ether ext. of the dried aerial parts of Hypericum papuanum. The tricyclic compds. (1-5) were named papuaforins A-E. The bicyclic compds. were isolated together with their corresponding tautomers and were named hyperguinones A and B (6/6a, 7/7a) and hyperpapuanone (8/8a), resp. Their structures were elucidated on the basis of extensive 1D and 2D NMR expts., as well as mass spectrometry. Furthermore, the cytotoxicity toward KB nasopharyngeal carcinoma cells and the antibacterial activity of the isolated compds. were detd