Marine Sponge-Derived Secondary Metabolites Modulate SARS-CoV-2 Entry Mechanisms.

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.