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Marine Sponge-Derived Secondary Metabolites Modulate SARS-CoV-2 Entry Mechanisms
Charlotte Steenblock1, Stefanie Richter2, Dirk Lindemann2
1Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Abstract:
The emergence of SARS-CoV 2 caused the COVID-19 pandemic, resulting in numerous global infections and deaths. In particular, people with metabolic diseases display an increased risk of severe COVID 19 and a fatal outcome. Treatment options for severe cases are limited, and the appearance of new virus variants complicates the development of novel therapies. To better manage viral infections like COVID 19, new therapeutic approaches are needed. Marine sponges offer a natural and renewable source of unique bioactive agents. These sponges produce secondary metabolites with various effects, including anti-viral, anti-inflammatory, and anti-tumorigenic properties. In the current study, we investigated the effect of five different marine sponge-derived secondary metabolites (four bromotyrosines and one sesquiterpenoid hydroquinone). Two of these, Avarol and Acetyl-dibromoverongiaquinol reduced the expression of ACE2, the main receptor for SARS-CoV 2, and the alternative receptor NRP1. Moreover, these substances derived from sponges demonstrated the ability to diminish the virus titer in SARS-CoV 2-infected cells, especially concerning the Omicron lineage. However, the reduction was not substantial enough to expect a significant impact on infected humans. Consequently, the investigated sponge-derived secondary metabolites are not likely to be effective to treat COVID 19 as a stand-alone therapy.
Insights
Marine sponges yield compounds that reduce SARS-CoV-2 entry and viral load in cells. However, these natural products are unlikely to be effective as a standalone COVID-19 treatment.
Area of Science:
- Marine natural products chemistry
- Virology
- Drug discovery
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, poses a significant global health threat.
- Individuals with metabolic diseases are at higher risk for severe COVID-19 outcomes.
- Limited treatment options and emerging variants necessitate novel therapeutic strategies.
Purpose of the Study:
- To investigate the antiviral potential of marine sponge-derived secondary metabolites against SARS-CoV-2.
- To evaluate the impact of these compounds on viral entry receptors (ACE2 and NRP1).
Main Methods:
- Screening of five marine sponge-derived secondary metabolites.
- Assessing the effect of compounds on ACE2 and NRP1 expression in infected cells.
- Quantifying viral titer reduction in SARS-CoV-2 infected cell cultures, including the Omicron variant.
Main Results:
- Two compounds, Avarol and Acetyl-dibromoverongiaquinol, reduced the expression of ACE2 and NRP1.
- These sponge-derived metabolites diminished SARS-CoV-2 viral titer in infected cells, particularly the Omicron lineage.
- The observed reduction in viral load was not substantial enough for significant clinical impact in humans.
Conclusions:
- Marine sponge metabolites show in vitro antiviral activity against SARS-CoV-2 by targeting entry receptors.
- While promising, these compounds are unlikely to be effective as a standalone therapy for COVID-19.
- Further research may explore synergistic effects or modifications for enhanced therapeutic potential.
