Anti-SARS-CoV-2 activity of cyanopeptolins produced by Nostoc edaphicum CCNP1411

Robert Konkel; Aleksandra Milewska; Nguyen Dan Thuc Do; Emilia Barreto Duran; Artur Szczepanski; Jacek Plewka; Ewa Wieczerzak; Sofia Iliakopoulou; Triantafyllos Kaloudis; Dirk Jochmans; Johan Neyts; Krzysztof Pyrc; Hanna Mazur-Marzec

doi:10.1016/j.antiviral.2023.105731

Anti-SARS-CoV-2 activity of cyanopeptolins produced by Nostoc edaphicum CCNP1411

Antiviral Res. 2023 Nov:219:105731. doi: 10.1016/j.antiviral.2023.105731. Epub 2023 Oct 12.

Affiliations

¹ Department of Marine Biology and Biotechnology, Faculty of Oceanography and Geography, University of Gdańsk, Gdynia, Poland.
² Virogenetics Laboratory of Virology, Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.
³ KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
⁴ Virogenetics Laboratory of Virology, Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland; Faculty of Chemistry, Jagiellonian University, Kraków, Poland.
⁵ Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
⁶ Department of Sustainable Agriculture, University of Patras, Agrinio, Greece.
⁷ Institute of Nanoscience & Nanotechnology, NCSR Demokritos, Agia Paraskevi, Greece; Laboratory of Organic Micropollutants, Water Quality Control Department, EYDAP SA, Menidi, Athens, Greece.
⁸ Virogenetics Laboratory of Virology, Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland. Electronic address: [email protected].
⁹ Department of Marine Biology and Biotechnology, Faculty of Oceanography and Geography, University of Gdańsk, Gdynia, Poland. Electronic address: [email protected].

PMID: 37838220
DOI: 10.1016/j.antiviral.2023.105731

Abstract

Despite the advances in contemporary medicine and availability of numerous innovative therapies, effective treatment and prevention of SARS-CoV-2 infections pose a challenge. In the search for new anti-SARS-CoV-2 drug candidates, natural products are frequently explored. Here, fifteen cyanopeptolins (CPs) were isolated from the Baltic cyanobacterium Nostoc edaphicum and tested against SARS-CoV-2. Of these depsipeptides, the Arg-containing structural variants showed the strongest inhibition of the Delta SARS-CoV-2 infection in A549^ACE2/TMPRSS2 cells. The functional assays indicated a direct interaction of the Arg-containing CP978 with the virions. CP978 also induced a significant decline in virus replication in the primary human airway epithelial cells (HAE). Of the four tested SARS-CoV-2 variants, Wuhan, Alpha, Omicron and Delta, only Wuhan was not affected by CP978. Finally, the analyses with application of confocal microscopy and with the SARS-CoV-2 pseudoviruses showed that CP978-mediated inhibition of viral infection results from the direct binding of the cyanopeptolin with the coronaviral S protein. Considering the potency of viral inhibition and the mode of action of CP978, the significance of the peptide as antiviral drug candidate should be further explored.

Keywords: Antiviral; Cyanopeptolins; Nostoc edaphicum; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Nostoc*
SARS-CoV-2
Spike Glycoprotein, Coronavirus

Substances

Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants
Nostoc edaphicum