Drug resistance will determine the use of a cocktail of...

Drug resistance will determine the use of a cocktail of antivirals targeting the same target .

The Pfizer drug Paxlovid is made up of two protease inhibitors so already advantageous to overcome resistance if it eventuates. There is currently only one mutation in the 3CL protease , an enzyme targeted by Pfizers antiviral pill Paxlovid the most advanced of the main protease Mpro target . Other Mpro targeting compounds are also in development and will be useful as combination drugs if multiple mutations develop.

BIT is going it alone targeting the E protein so far.


https://www.nature.com/articles/d41573-021-00202-8

During viral replication, SARS-CoV-2 synthesizes long polypeptides that must be cleaved into its constituent viral proteins. Mpro carries out most of this cleavage. Inhibiting Mpro thus prevents the virus from generating the proteins it needs to replicate.

“Mpro is a great target because it’s kind of the Achilles heel of the virus,” says Rolf Hilgenfeld, an antiviral researcher from the University of Lübeck, Germany.

https://www.medicalnewstoday.com/articles/pfizer-oral-antiviral-safe-and-effective-against-sars-cov-2

Dr. Adam Bailey, an assistant professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin–Madison, explained the rationale behind this duo of drugs to Medical News Today.

“These are both protease inhibitors. Drug cocktails that have the same target can often be a successful way to reduce the likelihood of drug [resistant] mutations cropping up. Instead of striking upon a single mutation that confers resistance to one drug, the virus must acquire two or more different mutations to generate resistance to both drugs simultaneously.”

"These are both protease inhibitors. Drug cocktails that have the same target can often be a successful way to reduce the likelihood of drug [resistant] mutations cropping up. Instead of striking upon a single mutation that confers resistance to one drug, the virus must acquire two or more different mutations to generate resistance to both drugs simultaneously"