Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has
recently emerged as a new public health threat. SARS-CoV-2 is the cause
of coronavirus disease (COVID-19) that has resulted in a global
pandemic. At the time of writing, approximately 6.6 million cases have
been reported worldwide. Like other coronaviruses, SARS-CoV-2 relies on
the surface Spike glycoprotein to access the host cells, mainly through
the interaction of its Receptor Binding Domain (RBD) with the host
receptor Angiotensin-Converting Enzyme2 (ACE2). SARS-CoV-2 infection
induces a profound downstream proinflammatory cytokine storm. This
release of the proinflammatory cytokines is underpinning lung tissue
damage, respiratory failure, and eventually multiple organ failure in
COVID-19 patients. The phosphorylation status of ERK1/2 is positively
correlated with virus load and ERK1/2 inhibition suppressed viral
replication and viral infectivity.Therefore, molecular entities able to
interfere with binding of the SARS-CoV-2 Spike protein to ACE2, or
damping hyperinflammatory cytokines storm, blocking ERK1/2
phosphorylation have a great potential to inhibit viral entry along with
viral infectivity. Herein, we report that the FDA-approved non-peptide
opioid antagonist drug, naltrexone suppresses high fat/LPS induced
pro-inflammatory cytokine release both from macrophage cells and Adipose
Tissue Macrophage (ATM). Moreover, Low Dose Naltrexone (LDN) also showed
its activity as an ERK1/2 inhibitor. Notably, virtual docking and
simulation data also suggest LDN may disrupt the interaction of ACE2
with RBD and thus LDN may be considered as a target as the treatment and
(or) adjuvant therapy for coronavirus infection.