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Biology subjects

Ruedin, Y.

Publications and source records attributed to Ruedin, Y..

2 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↗

Highly potent bispecific sybodies neutralize SARS-CoV-2

The ongoing COVID-19 pandemic represents an unprecedented global health crisis. Here, we report the identification of a synthetic nanobody (sybody) pair (Sb#15 and Sb#68) that can bind simultaneously to the SARS-CoV-2 spike-RBD and efficiently neutralize pseudotyped and live-viruses by interfering with ACE2 interaction. Two spatially-discrete epitopes identified by cryo-EM translated into the rational design of bispecific and tri-bispecific fusions constructs, exhibiting up to 100- and 1000-fold increase in neutralization potency. Cryo-EM of the sybody-spike complex further revealed a novel up-out RBD conformation. While resistant viruses emerged rapidly in the presence of single binders, no escape variants were observed in presence of the bispecific sybody. The multivalent bispecific constructs further increased the neutralization potency against globally-circulating SARS- CoV-2 variants of concern. Our study illustrates the power of multivalency and biparatopic nanobody fusions for the development of clinically relevant therapeutic strategies that mitigate the emergence of new SARS-CoV-2 escape mutants.

biochemistry↗