- ORCID
- 0000-0003-0925-2426
- ORCID
- 0000-0003-0355-7915
- LSF ID
- 11008
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- LSF ID
- 10905
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- LSF ID
- 57653
- ORCID
- 0000-0002-0335-6390
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
- ORCID
- 0000-0002-4763-1104
- ORCID
- 0000-0001-5269-8533
- LSF ID
- 59527
- ORCID
- 0000-0002-9211-5803
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
korrespondierende*r Autor*in
- GND
- 130213233
- LSF ID
- 16246
- ORCID
- 0000-0002-7003-6362
- Sonstiges
- der Hochschule zugeordnete*r Autor*in
korrespondierende*r Autor*in
- ORCID
- 0000-0001-7316-7141
- Sonstiges
- korrespondierende*r Autor*in
Abstract in Englisch:
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.