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Naltrexone a potential therapeutic candidate for COVID-19
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  • Abhinav Choubey,
  • Budheswar Dehury,
  • Sunil Kumar,
  • Bikash Medhi,
  • Prosenjit Mondal
Abhinav Choubey
IIT Mandi
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Budheswar Dehury
KiiT
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Sunil Kumar
ICAR-Indian Agricultural Statistical Research Institute
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Bikash Medhi
PGIMER
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Prosenjit Mondal
IIT Mandi
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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.