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Biology subjects

Engler, O.

Publications and source records attributed to Engler, O..

4 recordsLinked to original sources

Historical texts as a potential resource for plant-derived natural products against SARS-CoV-2 - the example of the Receptarium of Burkhard III von Hallwyl from 16th century Switzerland

In the search for more effective prophylactic and possibly curative therapeutics against SARS-CoV-2, an historical-ethnobotanical approach was used to select plants described in the Receptarium of Burkhard III von Hallwyl (RBH), an influential recipe text from 16th century Switzerland. Ten species were identified based on specific historical uses presumably linked with the treatment of viral infections as well as inflammatory conditions. For each plant candidate, aqueous and hydroethanolic extracts have been produced. CellTiter-Glo(R) Luminescent Cell Viability Assay was used to assess antiviral activity against SARS-CoV-2 and the effect on cell viability of the extracts. Of the ten plant species tested, four displayed an antiviral activity [&ge;] 50% at 16.7 {micro}g/ml with acceptable cell viability (> 75%): Sambucus nigra L. (leaves), Viola odorata L. (leaves), Geranium robertianum L. (arial parts) and Artemisia vulgaris L. (aerial parts). The crude extracts were partitioned in aqueous and organic fractions and further analyzed. The ethyl acetate fractions of S. nigra, V. odorata and G. robertianum expressed significant antiviral activity of nearly 100% at 5.6 {micro}g/ml (P < 0.05). The most potent inhibitory activity was observed for the ethyl acetate fraction of Viola odorata L. (leaves) with 87% at 1.9 {micro}g/ml (P < 0.0001). Alongside bioactivity analysis phytochemical fingerprints were made, with the aim to understand important substance classes contained. Further investigations are required to explore the active principles. Our study shows that an ethnopharmacological approach based on historical records of traditional use to select potential herbal candidates coupled with a rational screening process enables an efficient search for plant-derived natural products with antiviral activity against SARS-CoV-2.

pharmacology and toxicology↗

Molnupiravir combined with different repurposed drugs further inhibits SARS-CoV-2 infection in human nasal epithelium in vitro

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in late 2019, has caused a worldwide pandemic with unprecedented economic and societal impact. Currently, several vaccines are available, and multitudes of antiviral treatments have been proposed and tested. Although many of the vaccines show high clinical efficacy, they are not equally accessible worldwide. Additionally, due to the continuous emergence of new virus variants, and generally short duration of immunity, the development of safe and effective antiviral treatments remains of the utmost importance. Since the emergence of SARS-CoV-2, substantial efforts have been undertaken to repurpose existing and approved drugs for accelerated clinical testing and potential emergency use authorizations. However, drug-repurposing using high throughput screenings in cellular assays, often identify hits that later prove ineffective in clinical studies. Our approach was to evaluate the activity of compounds that have either been tested clinically or already undergone extensive preclinical profiling, using a standardized in vitro model of human nasal epithelium. Secondly, we evaluated drug combinations using sub-maximal doses of each active single compound. Here, we report the antiviral effects of 95 single compounds and 30 combinations. The data show that selected drug combinations including 10 M of molnupiravir, a viral RNA-dependent RNA polymerase (RdRp) inhibitor, effectively inhibit SARS-CoV-2 replication. This indicates that such combinations are worthy of further evaluation as potential treatment strategies against coronavirus disease 2019 (COVID-19).

microbiology↗

Multi-specific DARPin(R) therapeutics demonstrate very high potency against mutated SARS-CoV-2 variants in vitro

SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant to vaccine induced immunity and therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study of ensovibep, the first trispecific clinical DARPin candidate, that can simultaneously engage all three units of the spike protein trimer to potently inhibit ACE2 interaction, as revealed by structural analyses. The cooperative binding of the individual modules enables ensovibep to retain inhibitory potency against all frequent SARS-CoV-2 variants, including Omicron BA.1 and BA.2, as of February 2022. Moreover, viral passaging experiments show that ensovibep, when used as a single agent, can prevent development of escape mutations comparably to a cocktail of monoclonal antibodies (mAb). Finally, we demonstrate that the very high in vitro antiviral potency also translates into significant therapeutic protection and reduction of pathogenesis in Roborovski dwarf hamsters infected with either the SARS-CoV-2 wild-type or the Alpha variant. In this model, ensovibep prevents fatality and provides substantial protection equivalent to the standard of care mAb cocktail. These results support further clinical evaluation and indicate that ensovibep could be a valuable alternative to mAb cocktails and other treatments for COVID-19.

immunology↗

T-cell immunoglobulin and mucin (TIM) contributes to Hantaan virus entry into human airway epithelial cells

Hantaviruses are rodent-borne haemorrhagic fever viruses leading to serious diseases. Viral attachment and entry represent the first steps in virus transmission and are promising targets for antiviral therapeutic intervention. Here we investigated receptor use in human airway epithelium of the Old and New World hantaviruses Hantaan virus (HTNV) and Andes virus (ANDV). Using a biocontained recombinant vesicular stomatitis virus pseudotype platform, we provide first evidence for a role of the cellular phosphatidylserine (PS) receptors of the T-cell immunoglobulin and mucin (TIM) in HTNV and ANDV entry. In line with previous studies, HTNV, but not ANDV, was able to use the glycosaminoglycan heparan sulfate and v{beta}3 integrin as co-receptors. In sum, our studies demonstrate for the first time that hantaviruses use PS receptors and hence apoptotic mimicry to invade human airway epithelium, which may explain why these viruses can easily break the species barrier.

microbiology↗