Merck's molnupiravir should not be approved

I am sick of this armchair quarterbacking.

The internet is flooded with people who think that we just can’t risk vaccinating people because some 4th or 5th order effect just might lead to disaster when the 11th or 15th wave of the virus comes around.

Most antiviral drugs work by attacking the RNA replication process because many viruses depend on RNA replication or related processes such as reverse transcription. On the other hand, the organism just uses RNA for making proteins and a few errors in protein synthesis are not going to end your life cycle.

Flooding your body with fake RNA nucleotides or nucleosides (like the Merck drug or AZT or the Famciclovir I gave to my cat) certainly impairs viral replication but it is not a great strategy. If the virus is 1000 bp long and it takes 10 mutations to really trash it you are going to have to replace 1% of your nucleotides/sides with fakes so we are talking a big pill.

The paxlovid approach is better because it prevents virus particle formation in one step. The nucleotide/side analog thing slowed down AIDS but it was protease inhibitors (in combination with the old drugs and other new drugs!) that turned it from a death sentence to a chronic disease.

I think you’d be crazy to take molnupiravir instead of paxlovid not because molnupiravir is bad, but because paxlovid has much better efficacy. Rather than rambling on about hypothetical hazards, that person twitter should be telling you that.

Sadly, this is also what remdesivir does, although its an infusion. Also, the evolutionary pressure from vaccine-induced or natural antibodies also encourage mutations. The gamble is always complexity-related - will a random change help or hurt more.

People have also suggested a mixture of the Pfizer and Merck oral meds in order to reduce the chance of (quickly?) developing resistance to the protease. Similar to how HIV cocktails are used.