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15 results on '"Remm, Sille"'

8. Biparatopic sybodies neutralize SARS‐CoV‐2 variants of concern and mitigate drug resistance

Author

Walter, Justin D, primary, Scherer, Melanie, additional, Hutter, Cedric A J, additional, Garaeva, Alisa A, additional, Zimmermann, Iwan, additional, Wyss, Marianne, additional, Rheinberger, Jan, additional, Ruedin, Yelena, additional, Earp, Jennifer C, additional, Egloff, Pascal, additional, Sorgenfrei, Michèle, additional, Hürlimann, Lea M, additional, Gonda, Imre, additional, Meier, Gianmarco, additional, Remm, Sille, additional, Thavarasah, Sujani, additional, van Geest, Geert, additional, Bruggmann, Rémy, additional, Zimmer, Gert, additional, Slotboom, Dirk J, additional, Paulino, Cristina, additional, Plattet, Philippe, additional, and Seeger, Markus A, additional

Published
2022
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10. Synthetic nanobodies targeting the SARS-CoV-2 receptor-binding domain

Author

Walter, Justin D., Hutter, Cedric A.J., Zimmermann, Iwan, Earp, Jennifer, Egloff, Pascal, Sorgenfrei, Michèle, Hürlimann, Lea M., Gonda, Imre, Meier, Gianmarco, Remm, Sille, Thavarasah, Sujani, Plattet, Philippe, and Seeger, Markus A.

Abstract

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has resulted in a global health and economic crisis of unprecedented scale. The high transmissibility of SARS-CoV-2, combined with a lack of population immunity and prevalence of severe clinical outcomes, urges the rapid development of effective therapeutic countermeasures. Here, we report the generation of synthetic nanobodies, known as sybodies, against the receptor-binding domain (RBD) of SARS-CoV-2. In an expeditious process taking only twelve working days, sybodies were selected entirely in vitro from three large combinatorial libraries, using ribosome and phage display. We obtained six strongly enriched sybody pools against the isolated RBD and identified 63 unique anti-RBD sybodies which also interact in the context of the full-length SARS-CoV-2 spike protein. It is anticipated that compact binders such as these sybodies could feasibly be developed into an inhalable drug that can be used as a convenient prophylaxis against COVID-19. Moreover, generation of polyvalent antivirals, via fusion of anti-RBD sybodies to additional small binders recognizing secondary epitopes, could enhance the therapeutic potential and guard against escape mutants. We present full sequence information and detailed protocols for the identified sybodies, as a freely accessible resource. This report will be updated as we further characterize the identified sybodies, in terms of affinities, scaled-up purification yields, and their potential to neutralize SARS-CoV-2 infections.

Published
2020
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11. Biparatopic sybody constructs neutralize SARS-CoV-2 variants of concern and mitigate emergence of drug resistance

Author

Walter, Justin D., primary, Hutter, Cedric A.J., additional, Garaeva, Alisa A., additional, Scherer, Melanie, additional, Zimmermann, Iwan, additional, Wyss, Marianne, additional, Rheinberger, Jan, additional, Ruedin, Yelena, additional, Earp, Jennifer C., additional, Egloff, Pascal, additional, Sorgenfrei, Michèle, additional, Hürlimann, Lea M., additional, Gonda, Imre, additional, Meier, Gianmarco, additional, Remm, Sille, additional, Thavarasah, Sujani, additional, van Geest, Gerrit, additional, Bruggman, Rémy, additional, Zimmer, Gert, additional, Slotboom, Dirk J., additional, Paulino, Cristina, additional, Plattet, Philippe, additional, and Seeger, Markus A., additional

Published
2020
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12. Multicenter analysis of sputum microbiota in tuberculosis patients

Author

Sala, Claudia, primary, Benjak, Andrej, additional, Goletti, Delia, additional, Banu, Sayera, additional, Mazza-Stadler, Jesica, additional, Jaton, Katia, additional, Busso, Philippe, additional, Remm, Sille, additional, Leleu, Marion, additional, Rougemont, Jacques, additional, Palmieri, Fabrizio, additional, Cuzzi, Gilda, additional, Butera, Ornella, additional, Vanini, Valentina, additional, Kabir, Senjuti, additional, Rahman, S. M. Mazidur, additional, Nicod, Laurent, additional, and Cole, Stewart T., additional

Published
2020
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13. Critical discussion on drug efflux in Mycobacterium tuberculosis.

Author

Remm, Sille, Earp, Jennifer C, Dick, Thomas, Dartois, Véronique, and Seeger, Markus A

Subjects
*MYCOBACTERIUM tuberculosis, *MEMBRANE transport proteins, *SMALL molecules, *ATP-binding cassette transporters, *DRUG resistance, *ANTIBIOTICS, *DRUGS
Abstract

Mycobacterium tuberculosis (Mtb) can withstand months of antibiotic treatment. An important goal of tuberculosis research is to shorten the treatment to reduce the burden on patients, increase adherence to the drug regimen and thereby slow down the spread of drug resistance. Inhibition of drug efflux pumps by small molecules has been advocated as a promising strategy to attack persistent Mtb and shorten therapy. Although mycobacterial drug efflux pumps have been broadly investigated, mechanistic studies are scarce. In this critical review, we shed light on drug efflux in its larger mechanistic context by considering the intricate interplay between membrane transporters annotated as drug efflux pumps, membrane energetics, efflux inhibitors and cell wall biosynthesis processes. We conclude that a great wealth of data on mycobacterial transporters is insufficient to distinguish by what mechanism they contribute to drug resistance. Recent studies suggest that some drug efflux pumps transport structural lipids of the mycobacterial cell wall and that the action of certain drug efflux inhibitors involves dissipation of the proton motive force, thereby draining the energy source of all active membrane transporters. We propose recommendations on the generation and interpretation of drug efflux data to reduce ambiguities and promote assigning novel roles to mycobacterial membrane transporters. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Sybodies targeting the SARS-CoV-2 receptor-binding domain

Author

Walter, Justin D, primary, Hutter, Cedric A.J., additional, Zimmermann, Iwan, additional, Wyss, Marianne, additional, Egloff, Pascal, additional, Sorgenfrei, Michèle, additional, Hürlimann, Lea M, additional, Gonda, Imre, additional, Meier, Gianmarco, additional, Remm, Sille, additional, Thavarasah, Sujani, additional, Plattet, Philippe, additional, and Seeger, Markus A, additional

Published
2020
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