How Pfizer's New Drug Fights COVID (PAXLOVID)

[@ZeranZeran]

More people need to see this, very well done.

[@jcmoreutube]

Very well done! I didn’t understand anything but could not stop watching.

[@rafaelrodriguez2441]

Excelent channel. KZbin need more chemistry content like this!!!

[@SimplifyingSynthesis]

Glad you think so!

[@stevengill1736]

Always interesting to me to see the synthesis of modern pharmaceuticals, and looking at how the med binds to the receptors is neat too...cheers.

[@Medcram]

Thanks! Linked to this wonderful video in our video as well.

[@10000daddy]

Absolutely impressive. Must take so much time to put these videos together. Great job!

[@Back2Lobby334]

I dont understand, wont a basic hydrolysis of an ester make a caboxylate ion? Why on 8:11 do we have a caboxyl acid as a product when the basic hydrolysis gives a caboxylate ion.

[@SimplifyingSynthesis]

Yes it will form a carboxylate in the reaction mixture but it is protonated during the reaction workup

[@Back2Lobby334]

@@SimplifyingSynthesis Ahh of course 🤦‍♂ haha, thanks for the fast respons!

[@ahmedzakaria6085]

Very nice and informative... thank you so much.

[@adammohamed5256]

Keep up the hard work. Well done!

[@mohammadaminabdi2297]

Pure science

[@gabrielshaw2140]

Great Video!

[@gauravborkar3011]

Hi does the molecule not cyyclize internally with free amine and chlorine being present.

[@williamrobbins9195]

It seems that some of this compound will be cyclized in vitro. They may have factored this into the dosage forms. Excess of the medication will compensate for the losses of dimers and cyclization products.

[@captainkesh]

Awesome! that was brilliantly done. Thank you!

[@2ndia]

Amazing, thank you so much.

[@johnpeterson7264]

Wonderful presentation !

[@nutt.rangsiman]

Thanks for clear explanation.

[@MrVinceMru]

Very nice video. I have a newbie question: “Paxlovid targets the protease SARS CoV-2 3CLpro. Is this protease generic to each SARS CoV-2 Variant? Or is it uniquely based on the Wuhan strain or other specific variant / family of variants like Omicron)? If this protease were generic and we’re acting in the N-terminal Domain, then would it mean that we found a “permanent” solution to prevent viral virulence (severe form of SARS CoV-2) of the virus as a whole while not solving the infectious virulence?

[@SimplifyingSynthesis]

The protease varies slightly between different coronaviruses but the structure of the active site is very well conserved which allows a lot of the 3CL Pro targeting drugs to show activity against different virus. I'm not certain if there is any variation between different strains of SARs-CoV-2 with regards to the 3CL Protease but I would expect the drug to have a similar efficacy across all variants.

[@MrVinceMru]

Thank you for the quick reply! 😊 Indeed, we have seen up to now variations on the receptor binding domain, but not yet on the N-Terminal Domain yet, which you pointed out is well conserved. Let’s see if there will be immune escape mutations in the future, now that we are applying pressure to the N-terminal domain through binding of non-sterilising antibodies and use of 3CL Pro targeting drugs.

[@aemrt5745]

I heard that Paxlovid is leverage from HIV medication. Given how these drugs work, how easy would it be to dial in a new protease inhibitor for a new virus, or create them for existing diseases like chicken pox, pneumonia, meningitis, etc? In this field, my level of training is high school biology and undergrad inorganic chemistry.

[@SimplifyingSynthesis]

Its not easy but not impossible. We are getting a lot better at developing drugs that form covalent bonds with the enzyme selectively without much off-target binding that would cause toxic side effects

[@aemrt5745]

@@SimplifyingSynthesis Thank you.

[@carpo719]

Nice. You got a new sub for sure here. Can the protease inhibitor affect our own cellular replication in a negative way? It seems like it would not discriminate between covid,, and useful replications (perhaps many we do not understand, knowing our relationship with viruses) I have heard of birth defects and more with the Merck version, molnupiravir, are they similar?

[@SimplifyingSynthesis]

No the inhibitor is specific for the SARS-CoV enzyme and we haven't seen any strong inhibition of human enzymes at the dosages used. Like any drug it is possible to have side effects but the data so far indicates that it is well tolerated. I have a video on the Merck drug coming out later today. It causes mutations in the viral RNA but I don't know of any data that shows teratogenic activity in humans.

[@glzhang3127]

amazing content!

[@williamrobbins9195]

Great video

[@benjaminwong8326]

Awesome!

[@yavuzbahadrtaktak8020]

Great!

[@josefranciscodasilva2583]

👏👏👏👏

[@jakubswitalski7989]

Awesome video!