“There’s always a little bit of tension around

these issues of, well, is the drug going

to work, or not.”

Dr. Robert Shafer, Stanford infectious disease specialist

 

Good news from a phase 2 investigation pitting Molnupiravir (an oral antiviral agent still in clinical trials) against SARS-CoV-2.  After years of testing this-a-vir and that-a-vir in various labs, Molnupiravir and Remdesivir proved most likely to succeed.  Here’s the background story followed by the test results.

RNA viruses rely on their RNA-dependent polymerase (RdRP)* to stitch together  viral messenger RNA.  The sequenced mRNA in turn produces various proteins used for the production of new virions as the invading virus overtakes host cells. What’s needed for halting viral reproduction is a reliable RdRp inhibitor. Many those-a-virs created in labs have been tested against SARS-CoV-2. A successful compound will plop itself into the developing viral sequence causing mutations in the proteins and…hurray! no new offspring created. Remdesivir showed strong inhibition in lab and animal trials, and was subsequently approved for treatment in patients. Unfortunately, while it works well in toning down the severity of the illness thus speeding recovery, it requires IV infusion in a hospital setting and doesn’t reduce deaths in difficult cases. 

There are currently 246 antivirals in development. Creating antiviral meds is rather tricky, the difficulty being how to stop propagation of more virions produced within the host cell without killing the cell itself. Merck’s Molnupiravir, originally developed by Emory University then bought by Ridgeback Bio that sold it to Merck, originally targeted Influenza for Phase 1 animal trials. The drug proved to be effective at curbing flu infections in mice, guinea pigs, ferrets and human-airway organoids (human cells grown in petri dishes into viable tissues).. 

But then along came March, 2020 and the onset of SARS-CoV-2 which completely changed their plans. A successful test with ferrets proved that Molnupiravir blocked both developing cases as well as ferret to ferret transition. They went on to a Phase 2 safety trial with 202 outpatients with early symptoms of SARS-CoV-2. Those who received 400 or 800 mg. daily were completely free of virus by Day 5. Only 11.1% of the placebo group had similar clearance. Phase 2/3 testing is underway with results expected in September.

Here’s hoping!!