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Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: new tricks for old dogs
Egor V. Shekunov; Polina Z. Zlodeeva; Svetlana S. Efimova; Anna A. Muryleva; Vladimir V. Zarubaev; Alexander V. Slita; Olga S. Ostroumova.
  • Egor V. Shekunov; Institute of Cytology of Russian Academy of Sciences
  • Polina Z. Zlodeeva; Institute of Cytology of Russian Academy of Sciences
  • Svetlana S. Efimova; Institute of Cytology of Russian Academy of Sciences
  • Anna A. Muryleva; Saint-Petersburg Pasteur Institute of Epidemiology and Microbiology
  • Vladimir V. Zarubaev; Saint-Petersburg Pasteur Institute of Epidemiology and Microbiology
  • Alexander V. Slita; Saint-Petersburg Pasteur Institute of Epidemiology and Microbiology
  • Olga S. Ostroumova; Institute of Cytology of Russian Academy of Sciences
Preprint in English | bioRxiv | ID: ppbiorxiv-519140
ABSTRACT
With the resurgence of the coronavirus pandemic, the repositioning of FDA-approved drugs against coronovirus and finding alternative strategies for antiviral therapy are both important. We previously identified the viral lipid envelope as a potential target for the prevention and treatment of SARS-CoV-2 infection with plant alkaloids [1]. Here, we investigated the effects of eleven cyclic lipopeptides (CLPs), including well-known antifungal and antibacterial compounds, on the liposome fusion triggered by calcium, polyethylene glycol 8000, and a fragment of SARS-CoV-2 fusion peptide (816-827) by calcein release assays. Differential scanning microcalorimetry of the gel-to-liquid-crystalline and lamellar-to-inverted hexagonal phase transitions and confocal fluorescence microscopy demonstrated the relation of the fusion inhibitory effects of CLPs to alterations in lipid packing, membrane curvature stress and domain organization. The effects of the compounds were evaluated in an in vitro Vero-based cell model, and aculeacin A, anidulafugin, iturin A, and mycosubtilin attenuated the cytopathogenicity of SARS-CoV-2 without specific toxicity.

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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental Studies Language: English Year: 2022 Document Type: Preprint

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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental Studies Language: English Year: 2022 Document Type: Preprint