Astersaponin I from Aster koraiensis is a natural viral fusion blocker that inhibits the infection of SARS-CoV-2 variants and syncytium formation.

The continuous emergence of SARS-CoV-2 variants prolongs COVID-19 pandemic. Although SARS-CoV-2 vaccines and therapeutics are currently available, there is still a need for development of safe and effective drugs against SARS-CoV-2 and also for preparedness for the next pandemic. Here, we discover that astersaponin I (AI), a triterpenoid saponin in Aster koraiensis inhibits SARS-CoV-2 entry pathways at the plasma membrane and within the endosomal compartments mainly by increasing cholesterol content in the plasma membrane and interfering with the fusion of SARS-CoV-2 envelope with the host cell membrane. Moreover, we find that this functional property of AI as a fusion blocker enables it to inhibit the infection with SARS-CoV-2 variants including the Alpha, Beta, Delta, and Omicron with a similar efficacy, and the formation of syncytium, a multinucleated cells driven by SARS-CoV-2 spike protein-mediated cell-to-cell fusion. Finally, we claim that the triterpene backbone as well as the attached hydrophilic sugar moieties of AI are structurally important for its inhibitory activity against the membrane fusion event. Overall, this study demonstrates that AI is a natural viral fusion inhibitor and proposes that it can be a broad-spectrum antiviral agent against current COVID-19 pandemic and future outbreaks of novel viral pathogens.

Active search for COVID-19 cases during integrated supportive supervision using an electronic platform to improve healthcare workers performance in Niger: the legacy of the polio eradication program.

The implementation of electronic data collection during supportive supervision visits (ISS) using the Open Data Kits (ODK) Collection in Niger has provided a factual basis for monitoring the performance of the Polio eradication program (PEP) and the immunization program. With the notification of the first case of COVID-19 on 19 March 2020, there was a rapid need for quality knowledge to monitor the pandemic. For the first time in Niger, we initiated a six-month (May to October 2020) joint ISS-COVID-19 surveillance program to improve and monitor healthcare workers' performance to efficiently investigate COVID-19 cases in eight provinces. Overall, 1,378 ISS visits were performed through 390 health facilities, during which 4,638 health workers were trained and 527,151 medical records were reviewed, of which 28 suspected cases of COVID-19 were found. Field visits for contact tracing in their communities were accomplished and closed monitoring ensured until full recovery. Building on the tradition of PEP, a problem-solving process, feedback and on-the-job training on COVID-19 surveillance is set to enhance notification in the coming weeks and months. This is facilitated by accurate use of ODK Collect for real-time data surveillance successfully implemented. Other topics in the briefing included fundamentals of infection prevention and control for COVID-19 for both health professionals and community leaders. From this experience, the ISS has emerged as a key component of COVID-19 surveillance, especially in regions with a fragile health system. Our observation is a step forward for pragmatic interventional studies.

Anti-Inflammatory and Immunoregulatory Action of Sesquiterpene Lactones.

Sesquiterpene lactones (SL), characterized by their high prevalence in the Asteraceae family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure-activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure-activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.

Assessment of the Diversity of Medico-Magic Knowledge on Four Herbaceous Species in Benin.

BACKGROUND: Ethnobotanical knowledge on four herbaceous species, Acmella uliginosa (Sw.) Cass., Momordica charantia L., Phyllanthus amarus Schumach. & Thonn., and Scoparia dulcis L., in Benin was investigated. METHODS: Herbal medicine traders in six different markets were interviewed using a semi-structured questionnaire. The linear regression test was performed to check for the influence of respondent's age on ethnobotanical uses they hold. Relative frequency citation, fidelity level, use value, and Rahman similarity index were calculated to assess the diversity of medico-magic knowledge. The Informant Consensus Factor is not applicable in this study since we are dealing neither with the diversity of medicinal plants used by a community of people nor with a great number of plant species used for medicinal purposes, nor the diversity of plant species used in the treatment of a specific or group of ailments. RESULTS: The respondent's age did not influence the ethnobotanical uses they hold on the species. All thirty-six informants surveyed traded Phyllanthus amarus Schumach. & Thonn., Momordica charantia L., and Scoparia dulcis L., and the majority traded Acmella uliginosa (Sw.) Cass. The respondent's age does not influence the diversity of ethnobotanical uses they hold on the study species. Purchase in traders' own markets was the predominant source of Phyllanthus amarus Schumach. & Thonn., Momordica charantia L., and Scoparia dulcis L. while Acmella uliginosa (Sw.) Cass. was mostly purchased in other more distant markets. A noticeable proportion of traders also collect Phyllanthus amarus Schumach. & Thonn. and Momordica charantia L. from wild populations. Phyllanthus amarus Schumach. & Thonn. was the species most demanded by customers followed by Momordica charantia L. Traders confirmed the scarcity of all species in recent years and climate change and destruction of natural habitats for logging were the most cited causes. The entire plant of Phyllanthus amarus Schumach. & Thonn. was used mainly to treat malaria, diabetes, and constipation, and decoction with oral administration was the most frequent preparation for malaria treatment. To treat diabetes, informants mixed Phyllanthus amarus Schumach. & Thonn. with Momordica charantia L. used as a decoction with oral administration. Momordica charantia L. was also used to treat measles and chicken pox. Acmella uliginosa (Sw.) Cass. and Scoparia dulcis L. were mostly used for their spiritual use for luck, predominantly by chewing fresh leaves or flowers, and by bathing with the ground plant mixed with soap, respectively. Overall, Momordica charantia L. had the greatest use value followed by Phyllanthus amarus Schumach. & Thonn. The majority of traders do not plant the species. CONCLUSIONS: The harvesting and trade of the species threaten their natural populations and urgent tools, including in situ and ex situ conservation, are needed to ensure their long-term sustainable exploitation.

Antiviral Activity of Metabolites from Peruvian Plants against SARS-CoV-2: An In Silico Approach.

(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. (2) Methods: We applied in silico technics, such as virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA estimation. (3) Results: Rutin, a compound present in Peruvian native plants, showed affinity against three targets of SARS-CoV-2. The molecular dynamics simulation demonstrated the high stability of receptor-ligand systems during the time of the simulation. Our results showed that the Mpro-Rutin system exhibited higher binding free energy than PLpro-Rutin and N-Rutin systems through MM/GBSA analysis. (4) Conclusions: Our study provides insight on natural metabolites from Peruvian plants with therapeutical potential. We found Rutin as a potential candidate with multiple pharmacological properties against SARS-CoV-2.

Biologically Active Compounds in Stizolophus balsamita Inflorescences: Isolation, Phytochemical Characterization and Effects on the Skin Biophysical Parameters.

Three germacranolides, as well as five flavonoids, natural steroid and simple phenolic compounds, were isolated from the inflorescence of Stizolophus balsamita growing in Iran. The paper presents active compounds found for the first time in the inflorescence of this species. The flavonoids, simple phenolic compounds and natural steroids have been isolated for the first time in the genus Stizolophus. The MTT assay was employed to study in vitro cytotoxic effects of the taxifolin against human fibroblasts. We also evaluate the possible biological properties/cosmetic effects of Stizolophus balsamita extract and taxifolin on the human skin. Sixty healthy Caucasian adult females with no dermatological diseases were investigated. We evaluate the effects of S. balsamita extract and taxifolin on skin hydration and transepidermal water loss (TEWL). It was revealed that S. balsamita extract might decrease TEWL level and fixed the barrier function of the epidermis. The presence of bioactive phytochemical constituents in S. balsamita inflorescences makes them a valuable and safe source for creating new cosmetics and medicines.

Isodeoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber Linn., inhibits pro-inflammatory mediators' production through both NF-κB and AP-1 pathways in LPS-activated macrophages.

Isodeoxyelephantopin (IDET) has been identified as an anti-tumor natural constituent whose anti-tumor activity and mechanism have been widely investigated. Since the occurrence and development of cancer usually accompany with inflammation, and tumor signaling shares many components with inflammation signaling, the agents with anti-tumor activity are likely to possess anti-inflammation potential. Thus, the current study aims to demonstrate the anti-inflammatory activity along with the underlying mechanism of IDET in lipopolysaccharide (LPS)-primed macrophages. By using Griess method and ELISA, we found that in both bone marrow derived macrophages and alveolar macrophage cell line, IDET, at relatively low concentrations (0.75, 1.5 and 3 µM), could inhibit LPS-induced expression of various pro-inflammatory mediators including nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS), interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1) and IL-1ß. Meanwhile, in activated MH-S cells, the inhibitory action of IDET on mRNA expression levels of these cytokines was also detected using qPCR. Mechanistically, the effects of IDET on two key inflammatory signalings, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) pathways, were determined in LPS-activated MH-S cells by reporter gene along with western blot assays. On the one hand, IDET suppressed NF-κB signaling via down-regulating phosphorylation and degradation of inhibitor of NF-κB (IκB)-α and the subsequent p65 translocation. On the other hand, IDET dampened AP-1 signaling through attenuating phosphorylation of both c-jun N-terminal kinase 1/2 (JNK1/2) and extracellular signal regulated kinase 1/2 (ERK1/2). Our study indicates that IDET might be a promising constituent from the anti-inflammatory herb Elephantopus scaber Linn. in mitigating inflammatory conditions, especially respiratory inflammation.