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Advanced Molecular Tweezers with Lipid Anchors against SARS-CoV-2 and Other Respiratory Viruses
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Weil, Tatjana (author)
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Kirupakaran, Abbna (author)
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Le, My-Hue (author)
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Rebmann, Philipp (author)
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Mieres-Perez, Joel (author)
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Issmail, Leila (author)
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Conzelmann, Carina (author)
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Müller, Janis A. (author)
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Rauch, Lena (author)
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Gilg, Andrea (author)
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Wettstein, Lukas (author)
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Groß, Rüdiger (author)
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Read, Clarissa (author)
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Bergner, Tim (author)
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- Axberg Pålsson, Sandra, 1991- (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Uhlig, Nadja (author)
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Eberlein, Valentina (author)
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Wöll, Heike (author)
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Klärner, Frank-Gerrit (author)
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Stenger, Steffen (author)
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Kümmerer, Beate M. (author)
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Streeck, Hendrik (author)
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Fois, Giorgio (author)
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Frick, Manfred (author)
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Braubach, Peter (author)
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- Spetz, Anna-Lena, 1947- (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Grunwald, Thomas (author)
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Shorter, James (author)
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Sanchez-Garcia, Elsa (author)
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Schrader, Thomas (author)
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Münch, Jan (author)
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(creator_code:org_t)
- 2022-09-06
- 2022
- English.
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In: JACS Au. - : American Chemical Society (ACS). - 2691-3704. ; 2:9, s. 2187-2202
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- The COVID-19 pandemic caused by SARS-CoV-2 presents a global health emergency. Therapeutic options against SARS-CoV-2 are still very limited but urgently required. Molecular tweezers are supramolecular agents that destabilize the envelope of viruses resulting in a loss of viral infectivity. Here, we show that first-generation tweezers, CLR01 and CLR05, disrupt the SARS-CoV-2 envelope and abrogate viral infectivity. To increase the antiviral activity, a series of 34 advanced molecular tweezers were synthesized by insertion of aliphatic or aromatic ester groups on the phosphate moieties of the parent molecule CLR01. A structure-activity relationship study enabled the identification of tweezers with a markedly enhanced ability to destroy lipid bilayers and to suppress SARS-CoV-2 infection. Selected tweezer derivatives retain activity in airway mucus and inactivate the SARS-CoV-2 wildtype and variants of concern as well as respiratory syncytial, influenza, and measles viruses. Moreover, inhibitory activity of advanced tweezers against respiratory syncytial virus and SARS-CoV-2 was confirmed in mice. Thus, potentiated tweezers are broad-spectrum antiviral agents with great prospects for clinical development to combat highly pathogenic viruses.
Subject headings
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Keyword
- broad-spectrum antivirals
- SARS-CoV-2
- RSV
- molecular tweezers
- respiratory viruses
Publication and Content Type
- ref (subject category)
- art (subject category)
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JACS Au
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- By the author/editor
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Weil, Tatjana
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Kirupakaran, Abb ...
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Le, My-Hue
-
Rebmann, Philipp
-
Mieres-Perez, Jo ...
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Issmail, Leila
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show more...
-
Conzelmann, Cari ...
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Müller, Janis A.
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Rauch, Lena
-
Gilg, Andrea
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Wettstein, Lukas
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Groß, Rüdiger
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Read, Clarissa
-
Bergner, Tim
-
Axberg Pålsson, ...
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Uhlig, Nadja
-
Eberlein, Valent ...
-
Wöll, Heike
-
Klärner, Frank-G ...
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Stenger, Steffen
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Kümmerer, Beate ...
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Streeck, Hendrik
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Fois, Giorgio
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Frick, Manfred
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Braubach, Peter
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Spetz, Anna-Lena ...
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Grunwald, Thomas
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Shorter, James
-
Sanchez-Garcia, ...
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Schrader, Thomas
-
Münch, Jan
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
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JACS Au
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Stockholm University