Naltrexone a potential therapeutic candidate for COVID-19

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a global pandemic.
• Viral entry into host cells involves the Spike glycoprotein's Receptor Binding Domain (RBD) interacting with Angiotensin-Converting Enzyme 2 (ACE2).
• SARS-CoV-2 infection triggers a pro-inflammatory cytokine storm, leading to organ damage and failure. ERK1/2 phosphorylation correlates with viral load and promotes replication.

Purpose of the Study:

• To investigate the potential of naltrexone, specifically Low Dose Naltrexone (LDN), as a therapeutic agent against SARS-CoV-2.
• To assess LDN's ability to inhibit viral entry, reduce cytokine storms, and block ERK1/2 phosphorylation.

Main Methods:

• Assessed LDN's effect on pro-inflammatory cytokine release from macrophage cells and Adipose Tissue Macrophage (ATM).
• Evaluated LDN's activity as an ERK1/2 inhibitor.
• Utilized virtual docking and simulation to predict LDN's interaction with the SARS-CoV-2 RBD-ACE2 complex.

Main Results:

• LDN suppressed high fat/LPS-induced pro-inflammatory cytokine release.
• LDN demonstrated activity as an ERK1/2 inhibitor.
• Virtual simulations suggested LDN may disrupt the interaction between SARS-CoV-2 RBD and ACE2.

Conclusions:

• LDN exhibits potential as a treatment or adjuvant therapy for coronavirus infections.
• LDN's established safety profile as an FDA-approved drug (naltrexone) may obviate the need for extensive clinical toxicity testing.
• LDN's multifaceted mechanism, including potential disruption of viral entry and modulation of inflammatory responses, warrants further investigation.