Drugs Shown to Inhibit SARS-CoV-2 in COVID-19 Disease: Comparative Basic and Clinical Pharmacology of Molnupiravir and Ivermectin

The pharmacology of anti-SARS-CoV-2 drugs, Molnupiravir (M) and repurposed Ivermectin (IV) were compared. The IC50 for the inhibition of viral replication were 0.3μM for M and 2.8μM for IV. Both drugs have good oral absorption, with M achieving peak plasma concentrations by 2 hours and IV by 5 hours. The plasma half life were 7 hours for M and 81-91 hours for IV. M inhibits viral replication inducing viral mutagenesis in RdRp, causing viral error catastrophe and viral extinction. IV affects viral cell entry, nuclear transport and inhibits replication via RdRp. IV has additional effect to suppress cytokine production through STAT-3 inhibition. M is a more potent antiviral drug and IV has a longer residence in the body. Their effects on RdRp and cytokine inhibition are potentially complimentary for anti-COVID-19 activity. Both IV and M should be compared in randomized controlled clinical trials, and the possibility of their combination for anti-SARS-CoV-2 antiviral actions, explored further.