Nucleotide analog to clog Viral RNA Polyermase machinery in nCoV-2019

Remdesivir is for sale as of today, at $3,120 USD for the treatment of our current pandemic. Gilead Sciences has been devolping this Nucleotide analog for over 10 years. Nucleotide analogs look like one of the letters that DNA & RNA are made up of (this one looks like the letter “A”). But it isn’t that letter, it just looks like it, it’s analogous to it. So molecular machines that interact with these letters, nucleotides, accidentally end up using the analog instead and it messes things up.

RNA Polymerase Visualization from 2003

This old animation by Drew Berry at WEHI is still the best today. The blue molecule we see speeding through, with a growing yellow string behind it, that blue molecule is RNA Polymerase. All the little floating yellow bits, those are our letters, the nucleotides. Our Polymerase takes the floating yellow bits, and turns it into the long yellow string, the RNA. Coronoviruses have RNA genomes, that use the blue molecule to make copies of itself, Remdesivir looks like one of the floating yellow bits, so it gets sucked into the machine to make RNA, but instead it terminates the process.

As we see in the figure below, the replication pathway step involving RdRP (RNA-dependent RNA polymerase) is blocked by our nucleotide analog Remdesivir. This prevents the copying of the viral genetic code in the form of RNA.

However, we can see that the structure of the virus still gets made, this includes the spike, the envelope, and pretty much everything else to create a hollow sphere that looks like a crown on the outside; so the host immune system will still react to these particles, but they are empty and will not be able to propagate the virus.

Of course, these Nucleotide analogs also get incorporated into other cellular processes that use letters to read/write things, like our own genome and like the mitochondria or whatever. So that kinda sucks, but you know… it is what it is.