Chemical Composition of the Red Sea Green Algae Ulva lactuca: Isolation and In Silico Studies of New Anti-COVID-19 Ceramides.

Enas E Eltamany,Hashim A Hassanean,Sameh S Elhady,Eman S Habib,Amany K Ibrahim,Omar M Aly,Martin K Safo,Usama Ramadan Abdelmohsen,Marwa S Goda,Safwat A Ahmed

doi:10.3390/metabo11120816

Abstract

Coronavirus disease 2019 (COVID-19) is the disease caused by the virus SARS-CoV-2 responsible for the ongoing pandemic which has claimed the lives of millions of people. This has prompted the scientific research community to act to find treatments against the SARS-CoV-2 virus that include safe antiviral medicinal compounds. The edible green algae U. lactuca. is known to exhibit diverse biological activities such as anti-influenza virus, anti-Japanese encephalitis virus, immunomodulatory, anticoagulant, antioxidant and antibacterial activities. Herein, four new ceramides in addition to two known ones were isolated from Ulva lactuca. The isolated ceramides, including Cer-1, Cer-2, Cer-3, Cer-4, Cer-5 and Cer-6 showed promising antiviral activity against SARS-CoV-2 when investigated using in silico approaches by preventing its attachment to human cells and/or inhibiting its viral replication. Cer-4 and Cer-5 were the most effective in inhibiting the human angiotensin converting enzyme (hACE)–spike protein complex which is essential for the virus to enter the human host. In addition to this, Cer-4 also showed an inhibition of the SARS-CoV-2 protease (Mpro) that is responsible for its viral replication and transcription. In this study, we also used liquid chromatography coupled to electrospray ionization high-resolution mass spectroscopy (LC-ESI-HRMS) to identify several metabolites of U. lactuca, including metabolites such as fatty acids, their glyceride derivatives, terpenoids, sterols and oxysterols from the organic extract. Some of these metabolites also possessed promising antiviral activity, as previously reported.

Highlights

Coronaviruses (CoVs) are positive RNA genome viruses belonging to the Coronaviridae family of the Nidovirales order, which is divided into four genera (A, B, C, D)
The metabolic profiling of the crude extract of U. lactuca, performed using LC-ESIHRMS (Figures S1 and S2), showed the presence of a panel of diverse metabolites such as fatty acids, glycerides, sterols and oxysterols, ceramides, terpenoids, carbohydrates and amino acids (Table 1). These metabolites were detected by comparing their exact masses, with those recorded in databases, e.g., the Dictionary of Natural Products (DNP) and Metabolite and Chemical Entity (METLIN)
Previous assessment of the antiviral activity of various fatty acids revealed that medium-chain saturated and long-chain unsaturated fatty acids were highly active against enveloped viruses such as Vesicular stomatitis virus and Herpes simplex virus

Summary

Introduction

Coronaviruses (CoVs) are positive RNA genome viruses belonging to the Coronaviridae family of the Nidovirales order, which is divided into four genera (A, B, C, D). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the B genus [1]. CoVs have at least four structural proteins: namely spike protein, cover protein, membrane protein and nucleocapsid protein. The spike protein promotes host attachment and viral cell membrane fusion during virus infection [1]. Viruses often bind to receptor proteins on the surfaces of cells to enter human cells, for example, by linking with the human angiotensin-converting enzyme 2 (hACE2) receptor [3,4,5]. Protein–protein docking showed that SARS-CoV-2 spike proteins have a strong affinity for hACE2 [6]

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