Talk:Velpatasvir

ATC code missing
The ATC code seems to be missing. — Preceding unsigned comment added by Tommycarstensen (talk • contribs) 07:17, 7 August 2020 (UTC)

Mechanism of action seems erroneous
"Velpatasvir is an NS5A inhibitor" indicates that the drug is an inhibitor of the RNA-dependent RNA-polymerase (RdRP) of the virus, which is further detailed under "Mechanism of action", where it says:"The substance blocks NS5A, a protein necessary for hepatitis C virus replication and assembly."

But under "Interactions" it says:"Velpatasvir is both an inhibitor and a substrate of the transporter proteins P-glycoprotein (Pgp), ABCG2, OATP1B1 and OATP1B3". The latter means that Velpatasvir is an inhibitor of multidrug-resistance-transporters (MDR transporters). So I assume, since Velpatasvir is given in combination with Sofosbuvir, which is, itself, an NS5A-inhibitor (i.e. an RdRP-inhibitor), Velpatasvir is actually not an RdRP-inhibitor but given in combination with Sofosbuvir to prevent cells from exporting the actual RdRP-inhibitor (Sofosbuvir).

Furthermore, it is difficult to imagine a drug that is both a specific inhibitor of an RdRP and MDRs. Plus, the chemical structure of Velpatasvir looks nothing like the ones of RNA-polymerase inhibitors (which are nucletide analogues).

Could the author please look into the issue? --Felix Tritschler (talk) 19:17, 23 March 2020 (UTC)
 * Hi Felix! The virus's RNA-dependent RNA-polymerase is NS5B (not NS5A) and is inhibited by sofosbuvir. Velpatasvir inhibits NS5A, whose precise function seems to be somewhat unclear. (Our article says it might be a transcriptional activator.) I agree that, being a P-gp inhibitor, velpatasvir might also increase sofosbuvir levels, but at the moment I can't find a source supporting this. At any rate, velpatasvir does not seem to be a specific inhibitor of P-gp and OATPs, it just happens to block them like dozens or hundreds of other pharmaceuticals do. Best regards, ἀνυπόδητος (talk) 09:08, 24 March 2020 (UTC)

Incorrect structure
The structure in the article is incorrect - the ethoxy group in the lower-left part is supposed to be methoxymethyl - i.e. the oxygen should be moved one atom. 147.231.120.62 (talk) 05:54, 4 March 2024 (UTC)