Heparanase Blockade as a Novel Dual-Targeting Therapy for COVID-19.

Area of Science:

• Virology
• Immunology
• Pharmacology

Background:

• COVID-19, caused by SARS-CoV-2, leads to high mortality due to pneumonia and systemic inflammation.
• Heparanase (HPSE) regulates viral entry and inflammation, making it a potential therapeutic target.
• Existing COVID-19 therapies are insufficient, necessitating novel treatment strategies.

Purpose of the Study:

• To evaluate the efficacy of the heparanase inhibitor Roneparstat in treating COVID-19.
• To investigate Roneparstat's impact on SARS-CoV-2 infection and associated inflammation.
• To explore Roneparstat's potential as a dual-targeted therapy for COVID-19.

Main Methods:

• In vitro assessment of Roneparstat's antiviral activity against SARS-CoV-2 and other viruses.
• Single-cell RNA sequencing (scRNA-seq) analysis of bronchoalveolar lavage fluid from COVID-19 patients.
• Macrophage stimulation with SARS-CoV-2 S1 protein and subsequent treatment with Roneparstat.
• HPSE gene knockdown in macrophage cell lines.

Main Results:

• Roneparstat significantly reduced SARS-CoV-2, SARS-CoV-1, HTLV-1, and HIV-1 infectivity in vitro.
• Increased HPSE gene expression in macrophages correlated with COVID-19 severity and inflammatory cytokine levels (IL6, TNF, IL1B, CCL2).
• Roneparstat treatment attenuated S1 protein-induced inflammatory cytokine release by disrupting NF-κB signaling in macrophages.

Conclusions:

• Heparanase is a key target in SARS-CoV-2 pathogenesis.
• Roneparstat demonstrates broad-spectrum antiviral activity and anti-inflammatory effects.
• Roneparstat shows promise as a dual-targeted therapy to combat viral infection and inflammation in COVID-19.