Compounds derived from Humulus lupulus inhibit SARS-CoV-2 papain-like protease and virus replication.

BACKGROUND: Selected natural compounds exhibit very good antiviral properties. Especially, the medicinal plant Humulus lupulus (hop) contains several secondary plant metabolites some of which have previously shown antiviral activities. Among them, the prenylated chalcone xanthohumol (XN) demonstrated to be a potent inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). HYPOTHESIS/PURPOSE: Following the finding that xanthohumol (XN) is a potent inhibitor of SARS-CoV-2 Mpro, the effect of XN and its major derivatives isoxanthohumol (IXN), 6-prenylnaringenin (6-PN), and 8-prenylnaringenin (8-PN) from hops on SARS-CoV-2 papain-like protease (PLpro) were investigated. STUDY DESIGN: The modulatory effect of the hop compounds on PLpro were studied first in silico and then in vitro. In addition, the actual effect of hop compounds on the replication of SARS-CoV-2 in host cells was investigated. METHODS: In silico docking analysis was used to predict the binding affinity of hop compounds to the active site of PLpro. A recombinant PLpro was cloned, purified, characterized, and analyzed by small-angle X-ray scattering (SAXS), deISGylation assays, and kinetic analyses. Antiviral activity of hop compounds was assessed using the fluorescently labeled wildtype SARS-CoV-2 (icSARS-CoV-2-mNG) in Caco-2 host cells. RESULTS: Our in silico docking suggests that the purified hop compounds bind to the active site of SARS-CoV-2 PLpro blocking the access of its natural substrates. The hop-derived compounds inhibit SARS-CoV-2 PLpro with half maximal inhibitory concentration (IC50) values in the range of 59-162 µM. Furthermore, we demonstrate that XN and 6-PN, in particular, impede viral replication with IC50 values of 3.3 µM and 7.3 µM, respectively. CONCLUSION: In addition to the already known inhibition of Mpro by XN, our results show, for the first time, that hop-derived compounds target also SARS-CoV-2 PLpro which is a promising therapeutic target as it contributes to both viral replication and modulation of the immune system. These findings support the possibility to develop new hop-derived antiviral drugs targeting human coronaviruses.

A review on the environmental impact of phosphogypsum and potential health impacts through the release of nanoparticles.

Many industrial by-products have been disposed along coastlines, generating profound marine changes. Phosphogypsum (PG) is a solid by-product generated in the production of phosphoric acid (PA) using conventional synthesis methods. The raw material, about 50 times more radioactive as compared to unperturbed soils, is dissolved in diluted sulfuric acid (70%) forming PG and PA. The majority of both, reactive hazardous elements and natural radionuclides, remain bound to the PG. A nonnegligible fraction of PG occurs as nanoparticles (<0.1 µm). When PG are used for e.g., agriculture or construction purposes, nanoparticles (NPs) can be re-suspended by Aeolian and fluvial processes. Here we provide an overview and evaluation of the geochemical and radiological hazardous risks associated with the different uses of PG. In this review, we show that NPs are important residues in both raw and waste materials originating from the uses of phosphate rock. Different industrial processes in the phosphate fertilizer industries are discussed in the context of the chemical and mineralogical composition as well as size and reactivity of the released NP. We also review how incidental NPs of PG impact the global environment, especially with respect to the distribution of rare earth elements (REEs), toxic elements such as As, Se, and Pb, and natural radionuclides. We also propose the application of advanced techniques and methods to better understand formation and transport of NPs containing elements of high scientific, economic, and environmental importance.

Multiplexed Serum Antibody Screening Platform Using Virus Extracts from Endemic Coronaviridae and SARS-CoV-2.

The presence of antibodies against endemic coronaviruses has been linked to disease severity after SARS-CoV-2 infection. Assays capable of concomitantly detecting antibodies against endemic coronaviridae such as OC43, 229E, NL63, and SARS-CoV-2 may help to elucidate this question. We developed a serum screening platform using a bead-based Western blot system called DigiWest, capable of running hundreds of assays using microgram amounts of protein prepared directly from different viruses. Characterization of the immunoassay for detection of SARS-CoV-2 specific antibodies revealed a sensitivity of 90.3% and a diagnostic specificity of 98.1%. Concordance analysis with the SARS-CoV-2 immunoassays available by Roche, Siemens, and Euroimmun indicates comparable assay performances (Cohen's κ ranging from 0.8874 to 0.9508). Analogous assays for OC43, 229E, and NL63 were established and combined into one multiplex with the SARS-CoV-2 assay. Seroreactivity for different coronaviruses was detected with high incidence, and the multiplex assay was adapted for serum screening.

Practical advice on monitoring of U and Pu with marine bivalve mollusks near the Fukushima Daiichi Nuclear Power Plant.

Following the Fukushima Daiichi nuclear power plant accident in 2011, some marine radionuclide monitoring studies report a lack of evidence for contamination of Japanese coastal waters by U and Pu, or state that marine contamination by them was negligible. Nevertheless, Fukushima-derived U and Pu were reported as associated with Cs-rich microparticles (CsMPs) found in local soil, vegetation, and river/lake sediments. Over time, CsMPs can be transported to the sea via riverine runoff where actinides, as expected, will leach. We recommend establishing a long-term monitoring of U and Pu in the nearshore area of the Fukushima Prefecture using marine bivalve mollusks; shells, byssal threads and soft tissues should all be analyzed. Here, based on results from Th biosorption experiments, we propose that U and Pu could be present at concentrations several times higher in shells with a completely destroyed external shell layer (periostracum) than in shells with intact periostracum.

Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins.

Novel therapeutic options are urgently needed to improve global treatment of virus infections. Herbal products with confirmed clinical safety features are attractive starting material for the identification of new antiviral activities. Here we demonstrate that Cistus incanus (Ci) herbal products inhibit human immunodeficiency virus (HIV) infections in vitro. Ci extract inhibited clinical HIV-1 and HIV-2 isolates, and, importantly, a virus isolate with multiple drug resistances, confirming broad anti-HIV activity. Antiviral activity was highly selective for virus particles, preventing primary attachment of the virus to the cell surface and viral envelope proteins from binding to heparin. Bioassay-guided fractionation indicated that Ci extract contains numerous antiviral compounds and therefore has favorably low propensity to induce virus resistance. Indeed, no resistant viruses emerged during 24 weeks of continuous propagation of the virus in the presence of Ci extracts. Finally, Ci extracts also inhibited infection by virus particles pseudotyped with Ebola and Marburg virus envelope proteins, indicating that antiviral activity of Ci extract extends to emerging viral pathogens. These results demonstrate that Ci extracts show potent and broad in vitro antiviral activity against viruses that cause life-threatening diseases in humans and are promising sources of agents that target virus particles.

The root extract of the medicinal plant Pelargonium sidoides is a potent HIV-1 attachment inhibitor.

Global HIV-1 treatment would benefit greatly from safe herbal medicines with scientifically validated novel anti-HIV-1 activities. The root extract from the medicinal plant Pelargonium sidoides (PS) is licensed in Germany as the herbal medicine EPs®7630, with numerous clinical trials supporting its safety in humans. Here we provide evidence from multiple cell culture experiments that PS extract displays potent anti-HIV-1 activity. We show that PS extract protects peripheral blood mononuclear cells and macrophages from infection with various X4 and R5 tropic HIV-1 strains, including clinical isolates. Functional studies revealed that the extract from PS has a novel mode-of-action. It interferes directly with viral infectivity and blocks the attachment of HIV-1 particles to target cells, protecting them from virus entry. Analysis of the chemical footprint of anti-HIV activity indicates that HIV-1 inhibition is mediated by multiple polyphenolic compounds with low cytotoxicity and can be separated from other extract components with higher cytotoxicity. Based on our data and its excellent safety profile, we propose that PS extract represents a lead candidate for the development of a scientifically validated herbal medicine for anti-HIV-1 therapy with a mode-of-action different from and complementary to current single-molecule drugs.