Quinolizidines as Novel SARS-CoV-2 Entry Inhibitors.
COVID-19, caused by the highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread and become a pandemic since its outbreak in 2019. We have previously discovered that aloperine is a new privileged scaffold that can be modified to become a specific antiviral compound with markedly improved potency against different viruses, such as the influenza virus. In this study, we have identified a collection of aloperine derivatives that can inhibit the entry of SARS-CoV-2 into host cells. Compound 5 is the most potent tested aloperine derivative that inhibited the entry of SARS-CoV-2 (D614G variant) spike protein-pseudotyped virus with an IC50 of 0.5 µM. The compound was also active against several other SARS-CoV-2 variants including Delta and Omicron. Results of a confocal microscopy study suggest that compound 5 inhibited the viral entry before fusion to the cell or endosomal membrane. The results are consistent with the notion that aloperine is a privileged scaffold that can be used to develop potent anti-SARS-CoV-2 entry inhibitors.
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Related Subject Headings
- Virus Internalization
- SARS-CoV-2
- Quinolizidines
- Pandemics
- Humans
- HIV Fusion Inhibitors
- Chemical Physics
- COVID-19 Drug Treatment
- 3404 Medicinal and biomolecular chemistry
- 3107 Microbiology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Location
Related Subject Headings
- Virus Internalization
- SARS-CoV-2
- Quinolizidines
- Pandemics
- Humans
- HIV Fusion Inhibitors
- Chemical Physics
- COVID-19 Drug Treatment
- 3404 Medicinal and biomolecular chemistry
- 3107 Microbiology