Anti-SARS-CoV-2 and cytotoxic activity of two marine alkaloids from green alga <i>Caulerpa cylindracea</i> Sonder in the Dardanelles
Ebru Erol, Müge Didem Orhan, Timuçin Avşar, Atilla Akdemir, Emine Şükran Okudan, Gülbahar Özge Alim Toraman, Gülaçtı Topçu
Abstract
in the Dardanelles which resulted in the isolation of four compounds, caulerpin (1), monomethyl caulerpinate (2), beta-sitosterol (3), and palmitic acid (4). Their structures were elucidated by spectroscopic analyses including 1D- and 2D NMR and mass. The isolated compounds 1 and 2 were tested against the SARS-CoV-2 viral targets spike protein and main protease (3CL) enzyme, and both compounds significantly inhibit the interaction of spike protein and ACE2, while the main protease activity was not significantly reduced. Docking studies suggested that compounds 1 and 2 may bind to the ACE2 binding pocket on spike, and compound 2 may also bind to an allosteric site on spike. As such, these compounds may inhibit the spike-ACE2 complex formation competitively and/or allosterically and have the potential to be used against SARS-CoV-2 virus infection. In addition, compounds 1 and 2 showed at least two-fold higher cytotoxicity against breast cancer cell lines MCF7 and MDA-MB-231 compared to the CCD fibroblast control cell line.