Perilla (Perilla frutescens) leaf extract inhibits SARS-CoV-2 via direct virus inactivation.

BACKGROUND: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presents with mild or no symptoms in most cases, a significant number of patients become critically ill. Remdesivir has been approved for the treatment of coronavirus disease 2019 (COVID-19) in several countries, but its use as monotherapy has not substantially lowered mortality rates. Because agents from traditional Chinese medicine (TCM) have been successfully utilized to treat pandemic and endemic diseases, we designed the current study to identify novel anti-SARS-CoV-2 agents from TCM. METHODS: We initially used an antivirus-induced cell death assay to screen a panel of herbal extracts. The inhibition of the viral infection step was investigated through a time-of-drug-addition assay, whereas a plaque reduction assay was carried out to validate the antiviral activity. Direct interaction of the candidate TCM compound with viral particles was assessed using a viral inactivation assay. Finally, the potential synergistic efficacy of remdesivir and the TCM compound was examined with a combination assay. RESULTS: The herbal medicine Perilla leaf extract (PLE, approval number 022427 issued by the Ministry of Health and Welfare, Taiwan) had EC50 of 0.12 ± 0.06 mg/mL against SARS-CoV-2 in Vero E6 cells - with a selectivity index of 40.65. Non-cytotoxic PLE concentrations were capable of blocking viral RNA and protein synthesis. In addition, they significantly decreased virus-induced cytokine release and viral protein/RNA levels in the human lung epithelial cell line Calu-3. PLE inhibited viral replication by inactivating the virion and showed additive-to-synergistic efficacy against SARS-CoV-2 when used in combination with remdesivir. CONCLUSION: Our results demonstrate for the first time that PLE is capable of inhibiting SARS-CoV-2 replication by inactivating the virion. Our data may prompt additional investigation on the clinical usefulness of PLE for preventing or treating COVID-19.

Qualitative and Quantitative Analysis of Ukrainian Iris Species: A Fresh Look on Their Antioxidant Content and Biological Activities.

The major groups of antioxidant compounds (isoflavonoids, xanthones, hydroxycinnamic acids) in the rhizome methanol extracts of four Ukrainian Iris sp. (Iris pallida, Iris hungarica, Iris sibirica, and Iris variegata) were qualitatively and quantitatively analyzed using HPLC-DAD and UPLC-MS/MS. Gallic acid, caffeic acid, mangiferin, tectoridin, irigenin, iristectorigenin B, irisolidone, 5,6-dihydroxy-7,8,3',5'-tetramethoxyisoflavone, irisolidone-7-O-ß-d-glucopyranoside, germanaism B, and nigricin were recognized by comparing their UV/MS spectra, chromatographic retention time (tR) with those of standard reference compounds. I. hungarica and I. variegata showed the highest total amount of phenolic compounds. Germanaism B was the most abundant component in the rhizomes of I. variegata (7.089 ± 0.032 mg/g) and I. hungarica (6.285 ± 0.030 mg/g). The compound analyses showed good calibration curve linearity (r2 > 0.999) and low detection and quantifications limit. These results validated the method for its use in the simultaneous quantitative evaluation of phenolic compounds in the studied Iris sp. I. hungarica and I. variegata rhizomes exhibited antioxidant activity, as demonstrated by the HPLC-ABTS system and NRF2 expression assay and anti-inflammatory activity on respiratory burst in human neutrophils. Moreover, the extracts showed anti-allergic and cytotoxic effects against cancer cells. Anti-coronavirus 229E and lipid formation activities were also evaluated. In summary, potent antioxidant marker compounds were identified in the examined Iris sp.

Anti-inflammatory, antiallergic and COVID-19 protease inhibitory activities of phytochemicals from the Jordanian hawksbeard: identification, structure-activity relationships, molecular modeling and impact on its folk medicinal uses.

On Wednesday 11th March, 2020, the world health organization (WHO) announced novel coronavirus (COVID-19, also called SARS-CoV-2) as a pandemic. Due to time shortage and lack of either a vaccine and/or an effective treatment, many trials focused on testing natural products to find out potential lead candidates. In this field, an edible and folk medicinal Jordanian plant Crepis sancta (Asteraceae) was selected for this study. Phytochemical investigation of its enriched polyphenolic extract afforded four eudesmane sesquiterpenes (1-4) together with (6S,9R)-roseoside (5) and five different methylated flavonols (6-10). Structure elucidation of isolated compounds was unambiguously determined based on HRESIMS, X-ray crystallography, and exhaustive 1D and 2D NMR experiments. All isolated compounds were assessed for their in vitro anti-inflammatory, antiallergic and in silico COVID-19 main protease (Mpro) inhibitory activities. Among the tested compounds, compounds 5-10 revealed potent anti-inflammatory, antiallergic and COVID-19 protease inhibitory activities. Chrysosplenetin (10) is considered as a promising anti-inflammatory and antiallergic lead structure adding to the phytotherapeutic pipeline. Moreover, its inhibitory activity against SARS-CoV-2 Mpro, supported by docking and molecular dynamic studies, strengthens its potential as a lead structure paving the way toward finding out a natural remedy to treat and/or to control the current COVID-19 pandemic.

A CMOS-compatible poly-Si nanowire device with hybrid sensor/memory characteristics for System-on-Chip applications.

This paper reports a versatile nano-sensor technology using "top-down" poly-silicon nanowire field-effect transistors (FETs) in the conventional Complementary Metal-Oxide Semiconductor (CMOS)-compatible semiconductor process. The nanowire manufacturing technique reduced nanowire width scaling to 50 nm without use of extra lithography equipment, and exhibited superior device uniformity. These n type polysilicon nanowire FETs have positive pH sensitivity (100 mV/pH) and sensitive deoxyribonucleic acid (DNA) detection ability (100 pM) at normal system operation voltages. Specially designed oxide-nitride-oxide buried oxide nanowire realizes an electrically V(th)-adjustable sensor to compensate device variation. These nanowire FETs also enable non-volatile memory application for a large and steady V(th) adjustment window (>2 V Programming/Erasing window). The CMOS-compatible manufacturing technique of polysilicon nanowire FETs offers a possible solution for commercial System-on-Chip biosensor application, which enables portable physiology monitoring and in situ recording.

Transcranial magnetic stimulation after conditioning stimulation in two adrenomyeloneuropathy patients: delayed but facilitated motor-evoked potentials.

Two male patients were diagnosed with adrenomyeloneuropathy. Their chief problems were progressive spastic paraparesis, sensory impairment, hyperpigmentation and testis atrophy. Transcranial magnetic stimulation (TMS) does not easily elicit motor-evoked potentials (MEPs) in patients with a central nervous system dysfunction, even though a few methods, such as contraction of the target muscles and the Jendrassik maneuver (JM), are used in the attempt to facilitate them. In these two patients, we used a conditioning method (prior electrical stimulation over the cutaneous nerve of the left index finger) in order to facilitate MEPs, elicited by TMS, in the left tibialis anterior muscle. In patient 1, facilitation of MEPs was present at conditioning-test (C-T) intervals in the range 60-220 ms, with the maximal MEP recorded at C-T 160 ms; in patient 2, it occurred in the C-T interval range 110-140 ms, with the maximal MEP recorded at C-T 130 ms. By means of conditioning electrical stimulation, we can facilitate MEPs elicited by TMS in those subjects in whom MEPs are minimal or difficult to elicit even using the conventional JM or muscle contraction. The facilitation of MEPs by conditioning stimuli allowed us not only to assess central motor conduction time, but also to demonstrate the preserved continuity of the corticospinal tract in these two patients.