Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CLpro and PLpro

Abstract

A global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides excellent drug targets. Papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro) play a vital role in polyprotein processing, producing functional non-structural proteins essential for viral replication and survival in the host cell. Moreover, PLpro is employed by SARS-CoV-2 for reversing host immune responses. Therefore, if some particular compound has the potential to interfere with the proteolytic activities of 3CLpro and PLpro of SARS-CoV-2, it may be effective as a treatment or prophylaxis for COVID-19, reducing viral load, and reinstating innate immune responses. Thus, the present study aims to inhibit SARS-CoV-2 through 3CLpro and PLpro using marine natural products isolated from marine algae that contain numerous beneficial biological activities. Molecular docking analysis was utilized in the present study for the initial screening of selected natural products depending on their 3CLpro and PLpro structures. Based on this approach, Ishophloroglucin A (IPA), Dieckol, Eckmaxol, and Diphlorethohydroxycarmalol (DPHC) were isolated and used to perform in vitro evaluations. IPA presented remarkable inhibitory activity against interesting drug targets. Moreover, Dieckol, Eckmaxol, and DPHC also expressed significant potential as inhibitors. Finally, the results of the present study confirm the potential of IPA, Dieckol, Eckmaxol, and DPHC as inhibitors of SARS-CoV-2. To the best of our knowledge, this is the first study that assesses the use of marine natural products as a multifactorial approach against 3CLpro and PLpro of SARS-CoV-2.

Marine natural products

“…345,346 An in silico study of various brown algal phlorotannins as SARS-COV-2 protease inhibitors identied several lead compounds, which were then validated as weak to moderate inhibitors using in vitro bioassays. 347 One study has examined the effects of temperature and light on lipid production in two different Streblonema algae, with the concentrations of various polar glycerol-derived metabolites varying signicantly following exposure to low or high light intensities. 348 The structure of a tetraprenylated chromane has been revised to 883 following in-depth J-based congurational analysis coupled with comparison of experimental and calculated chiro-optical properties.…”

The Role of Seaweed Polysaccharides in Gastrointestinal Health: Protective Effect against Inflammatory Bowel Disease

“…Seaweed consists of high amounts of polysaccharides, proteins, and polyphenols. Polyphenols from marine seaweed have been studied for their therapeutic activities, such as anti-viral, antioxidant, and photoprotective activities [14][15][16]. Research on the potential for employing complex marine polysaccharides as medicinal agents has been explored extensively.…”

Sulfated Polysaccharides from Seaweeds: A Promising Strategy for Combatting Viral Diseases—A Review

“…Algal polysaccharides are essential for many biological processes, including cell–cell communication, cell growth, and immune system molecular recognition. The therapeutic properties of polysaccharides include antimicrobial, antifungal, antiviral, antidiabetic, anticancer, antioxidative, anti-inflammatory, immunoregulatory, and prebiotic activities [ 22 , 23 , 24 , 25 , 26 ]. Anionic polymers include sulfated polysaccharides.…”