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A key strategy to mitigate postprandial hyperglycemia involves inhibiting α-amylases, which commence the starch digestion process in the gut. This study examined the inhibitory effects of resveratrol and stilbenoid tetramers, vaticanol B, (-)-hopeaphenol, and vatalbinoside A on human salivary and pancreatic α-amylases experimentally and through molecular docking studies. Vaticanol B demonstrated the most potent inhibition with IC 50 values of 5.3 ± 0.3 μM for salivary and 6.1 ± 0.5 μM for pancreatic α-amylase (compared to acarbose with IC 50 values of 1.2 ± 0.1 μM and 0.5 ± 0.0 μM, respectively). Kinetic analysis suggested a competitive inhibition mode for vaticanol B. Resveratrol and vatalbinoside A were poor inhibitors of human α-amylases, while (-)-hopeaphenol exhibited moderate inhibition. Molecular docking supported the inhibition data, and several aspects of the structural configurations explained the stronger inhibition exerted by vaticanol B. Overall, vaticanol B shows promise as a natural alternative to acarbose for inhibiting α-amylase.

In the current study we investigate the antifouling potential of three polyphenolic resveratrol multimers (-)-hopeaphenol, vaticanol B and vatalbinoside A, isolated from two species of Anisoptera found in the Papua New Guinean rainforest. The compounds were evaluated against the growth and settlement of eight marine microfoulers and against the settlement and metamorphosis of Amphibalanus improvisus barnacle cyprids. The two isomeric compounds (-)-hopeaphenol and vaticanol B displayed a high inhibitory potential against the cyprid larvae metamorphosis at 2.8 and 1.1 μM. (-)-Hopeaphenol was also shown to be a strong inhibitor of both microalgal and bacterial adhesion at submicromolar concentrations with low toxicity. Resveratrol displayed a lower antifouling activity compared to the multimers and had higher off target toxicity against MCR-5 fibroblasts. This study illustrates the potential of natural products as a valuable source for the discovery of novel antifouling leads with low toxicity.

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (-)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production. In contrast, it does not substantially inhibit the early PKC-mediated T-cell activation marker CD69 production of IL-6 or NF-κB signaling induced by tumor necrosis factor alpha (TNF-α). We further show that hopeaphenol can inhibit cyclin-dependent kinase 9 (CDK9) enzymatic activity required for HIV transcription. Finally, it inhibits HIV replication in peripheral blood mononuclear cells (PBMCs) infected in vitro and dampens viral reactivation in CD4 + cells from PLWH. Our study identifies hopeaphenol as a novel inhibitor that targets a subset of PKC-mediated T-cell activation pathways in addition to CDK9 to block HIV expression. Hopeaphenol-based therapies could complement current antiretroviral therapy otherwise not targeting cell-associated HIV RNA and residual antigen production in PLWH.

The COVID-19 pandemic has highlighted the significance of every role within the interdisciplinary team and has exacerbated the challenges posed to every member. From the nursing perspective, many of these challenges were present before the pandemic but have become significantly larger problems that continue to demand global attention. This has provided an opportunity to critically evaluate and learn from the challenges the pandemic has both highlighted and created. We conclude that the nursing infrastructure requires a revolution in order to support, grow and retain nurses, who are vital to the delivery of high-quality healthcare., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © 2022, Radcliffe Cardiology.)

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 (IC 50 ) of 0.11 μM, in contrast to an IC 50 of 28.3 μM 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 VSVΔG-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 [EC 50 s], 10.2 to 23.4 μM) without cytotoxicity and approaching the activities of the control antiviral remdesivir (EC 50 s, 1.0 to 7.3 μM). 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.

Due to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has renewed the interest in exploring natural products as anthelmintics. In the present study, we screened 7500 plant extracts for in vitro-activity against the barber's pole worm, Haemonchus contortus, a highly significant pathogen of ruminants. The anthelmintic extracts from two plants, Cryptocarya novoguineensis and Piper methysticum, were fractionated by high-performance liquid chromatography (HPLC). Subsequently, compounds were purified from fractions with significant biological activity. Four α-pyrones, namely goniothalamin (GNT), dihydrokavain (DHK), desmethoxyyangonin (DMY) and yangonin (YGN), were purified from fractions from the two plants, GNT from C. novoguineensis, and DHK, DMY and YGN (= kavalactones) from P. methysticum. The three kavalactones induced a lethal, eviscerated (Evi) phenotype in treated exsheathed third-stage larvae (xL3s), and DMY and YGN had moderate potencies (IC 50 values of 31.7 ± 0.23 μM and 23.7 ± 2.05 μM, respectively) at inhibiting the development of xL3s to fourth-stage larvae (L4s). Although GNT had limited potency (IC 50 of 200-300 μM) at inhibiting L4 development, it was the only compound that reduced L4 motility (IC 50 of 6.25-12.50 μM). The compounds purified from each plant affected H. contortus in an irreversible manner. These findings suggest that structure-activity relationship studies of α-pyrones should be pursued to assess their potential as anthelmintics., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Two prenylated benzophenones, guttiferones O (1) and P (2), were isolated from the stem bark of the Papua New Guinean plant Garcina solomonensis. The structures of these compounds and their relative configurations were determined by spectroscopic methods. Both compounds inhibited the phosphorylation of the synthetic biotinylated peptide substrate KKLNRTLSVA by the serine/threonine protein kinase MAPKAPK-2 with IC(50) values of 22.0 microM.

Bioassay-guided fractionation of an organic extract from the leaves of Cupaniopsis macropetala resulted in the isolation of a new alkaloid, galloyl tyramine ( 1), together with the known flavonoid glycoside quercitrin ( 2). The structure of 1 was determined following 1D and 2D NMR, IR, UV, and MS data analysis. Compounds 1 and 2 displayed IC 50 values of 161 and 25 microM, respectively, in a Pim2 enzyme assay.