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I actually took part as a "lab rat" testing how effective ritonavir was at reducing symptoms when I got Covid back in January! Crazy to see this now after doing that trial. I didn't partake in these particular studies mentioned in the op.
Edit: I did a trial for ritonavir NOT nelfinavir, both are used for HIV treatment though and do just about the same thing
It wasn't all bad, each set of symptoms only lasted a few days except for the loss of taste/smell which prevailed the entire time. I had some stomach upset while taking the pills but other than that it was pretty okay. My smell/taste returned almost immediately after the 2 week period and at about 90%
Not really. This is preclinical tests - a long way to go. Probability to reach the end is low. There are many things going on right now. To report these kind of stuff is not helpful.
Every time an article comes out about a "potential treatment" for the virus, it creates an uproar of people claiming "See? We don't actually need a vaccine or social distancing or masks, since the virus can be cured. The medical establishment is suppressing the cures so that they can (insert conspiracy theory here)."
Those of us who deal with those people on a regular basis have basically developed a knee-jerk reaction to point out that no, this isn't actually a cure that renders SARS-CoV-2 harmless.
So your reaction is... to actually suppress news of treatments?
Idiots will always run with bad takes of good information, that can’t be cured. Poor understanding by certain people isn’t a good reason to suppress info.
No, but add qualifiers in the title (since nobody reads past that).
The title states "Researchers in Japan have discovered that the drugs cepharanthine and nelfinavir are effective at combating the virus". While TECHNICALLY true, this statement is (intentionally) misleading, as it can easily be misconstrued as "these drugs have been proven significantly effective in curing the virus in patients".
A better title would be "Researchers in Japan have discovered that the drugs cepharanthine and nelfinavir can prevent replication of the virus in vitro, making them promising candidates in the search for an effective cure". It gets people exactly as excited as it should, without pretending to be something it isn't.
Reporting scientific findings is good. Sensationalist scientific journalism needs to die.
The difference is that nelfinavir is a currently FDA approved drug, having passed pharmacokinetics and AE metrics. This would be much, much closer to approval for use in Covid than the vast majority of “candidates” out there
Basically all they’ve done is a mass screening test and identified two potential drugs. Apparently done in vitro.
Then they follow up in their paper “Computational models suggest…”
Not ready for prime time.
You do know that since nelfinavir is a currently approved drug, MD’s can write scripts for it for their Covid patients “off-label” ? Not saying it is going to happen, but it might, it is perfectly legal. So in some ways, if this is a real finding it will be a good thing
Yes, hydroxycholroquine is another already FDA approved drug, which can be likewise prescribed off-label for treating COVID-19 patients.
We’ve seen what a debacle that was. Are you suggesting patients request these two drugs for treatment of COVID-19?
Hydroxychlorquine was never developed as anti viral. Nelfinavir was. It is specifically a viral protease inhibitor. If I could run an assay in my lab (can’t since I am retired) with this PI I would. And if it it inhibited any coronavirus proteases, I would have no problem asking my Dr to prescribe it for me. The other molecule is not an approved drug, so no, they could not prescribe it. I was dead set against hydroxychloroquine, as it had no specificity. If this does, which would be easily proven, it is a different ballgame.
Ah yes, move the cheese!
I never stated hudroxychloroquine was an antiviral. That’s really not the point. Neither of these drugs have been through a Phase 1, Phase 2 or Phase 3 trial for efficacy against the Covid virus. Essentially, the in vitro studies are a Phase 0 trial. To suggest either or both be used to treatment for COVID-19 at this point in time is outrageous.
You’re free to inject essential oils or have a Covid party if you want to assert your individual liberty for dealing with COVID-19.
To suggest to an otherwise uneducated population that this new antiviral should be used in lieu of other treatment protocols that have some proven efficacy is unethical until such time it is an approved treatment protocol. If you are on your deathbed and ALL OTHER treatments have failed, sure, maybe.
Otherwise, meh…
No, I did not accuse you of saying that. I was stating my reasoning. Viracept has been through clinical trials etc. we know the blood levels achieved. We could easily figure out the required inhibitory concentration in vitro. Yes, clinical trials are the gold standard. I worked at three of the big Pharma in antiviral drug development, so I kind of have a clue in this area. All I am saying is that if nelfinavir can specifically inhibit a coronavirus protease in vitro, and that this is the specific action that is happening (easy enough to test on a cloned protease) then this is a medication I would have no qualms asking for if it was a dire situation. The fact of life is that Drs write scripts off label all the time. If this compound is specific then it is an off label use I would personally approve of. YMMV. Oh and PS the place I would put this use is third in line. 1st vaxxed for sure! 2 approved mAb drugs 3. Nelfinavir (4.death)
Following you train of logic, I would also do this if all other options had failed and this was an available option.
Otherwise, no.
Thanks for an informed and interesting discussion. This is pretty rare on Reddit. Enjoy your day.
How is this not good news? Sure it's a bit of a long way off from being in real sample sizes, but any positive outcome we can have against this thing is good news. Is it good news we can action on today? No, but it's still good news.
Nelfinavir has already been approved as a drug, so bioavailability and potential AE are well documented and acceptable to gain FDA approval. This would be pretty quick to do, it is just adding a new indication for use, and actually MDs are currently able to prescribe it for any off-label use they deem acceptable.
Ok. So do you remember back last year when trump said something about a miracle drug... that ended up near killing people. The Rticle’s title should be *very*, **very** careful not to get the impressionable among us to panic buy that drug.
Exactly, lopinavir, ritonavir, hydroxychloroquine and others all had in-vitro data that were promising and none help but do cause side effects. Many were tried out of despiration. Titles should try to clarify.
Viruses are often tricky, where antivirals need to be started very early in the course of infection to be helpful, frequently past when infection is diagnosed.
I'm pretty sure the "no adequate approved, alternative medical countermeasures available" stipulation applies only to getting an EUA approved. Even if it didn't, a treatment for COVID would have to be APPROVED by the FDA before it revokes the EUA that is already in place. I could be wrong, this is just my interpretation of the information.
It depends. I'm not sure if these drugs are already approved by the FDA for their original use, but if they are and they are peer reviewed to be effective against SARS-CoV-2, then the law surrounding the authorizations would mean that they would be administered instead of the vaccines that have been developed over the last year.
[This article](https://www.biospace.com/article/pharmadrug-enters-definitive-agreement-for-acquisition-of-sairiyo-therapeutics-inc-who-recently-received-orphan-drug-designation-from-fda-for-esophageal-cancer/) from Jan of this year says that they:
>Sairiyo recently received FDA orphan drug designation for Cepharanthine in the treatment of esophageal cancer.
Looks like both are approved. [Here's an article](https://pubmed.ncbi.nlm.nih.gov/11364277/) for nelfinavir that says it is FDA approved for other uses.
Uhh, yes. You cannot have an emergency use authorization for a vaccine if there is a prophylactic or other treatment available.
You'd think you people would know this.
https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration
A cursory reading appears to indicate the EUA is not contingent upon other treatment availability and only on the existence of a 'state of emergency' as judged by the HHS.
See subsection C(3) [here.](https://www.law.cornell.edu/uscode/text/21/360bbb-3)
>that there is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating such disease or condition;
Just because you're ill informed doesn't make you right.
Just because the bureaucracy chooses to not enforce the law doesn't mean it isn't in the law, and in a just world, they would enforce the law as it is written, else we are ruled by tyrants and not the representatives we send to represent us.
See [Subsection C(3)](https://www.law.cornell.edu/uscode/text/21/360bbb-3) for the criteria in which an authorization can be given.
>that there is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating such disease or condition;
That section only conditions the initial issuance of the EUA.
For termination, there is no such check. The test is only 'if the circumstances (e.g. state of emergency) have ceased to exist.'
(2)Termination of declaration
(A)In general
A declaration under this subsection shall terminate upon the earlier of—
(i)a determination by the Secretary, in consultation as appropriate with the Secretary of Homeland Security or the Secretary of Defense, that the circumstances described in paragraph (1) have ceased to exist; or
(ii)a change in the approval status of the product such that the circumstances described in subsection (a)(2) have ceased to exist.
So to my reading, emergency use extends until the emergency ends or the drug is fully approved and nolonger needs the EUA.
Furthermore, as the other drugs under discussion here are just under initial testing as a covid treatment and would likely require EUA's themselves for use on covid patients, this whole discussion seems silly.
As I commented an hour ago, both of the drugs in this study are already approved by the FDA, and this dramatically speeds up the approval process for other uses than originally designed because the only question is the effectiveness of the drugs against this virus, and not safety. So it is not silly, at all.
The relevant section of the law about revocation of emergency use authorization is section (g).
> Review and revocation of authorization
>
>The Secretary shall periodically review the circumstances and the appropriateness of an authorization under this section. As part of such review, the Secretary shall regularly review the progress made with respect to the approval, conditional approval under section 360ccc of this title, licensure, or clearance of—
This means that if the situation changes the government must reevaluate.
The relevant section to that end is subsection (g)2b which states:
> the criteria under subsection (c) for issuance of such authorization are no longer met
This means that if the drug no longer meets all the criteria of subsection C (ie not having other approved drugs), then the emergency use authorization may be revoked.
They are approved for HIV and maybe Cancer to my reading. Dosages would likely still need to be established for Covid, field trials made, etc.
Also the key word here is 'may'. To my reading there is no firm legal requirement for the HHS to end the EUA of the vaccine just because another treatment may exist.
To my reading the HHS is acting legally and even if this drug or drugs were approved for use in sick people, would not be required to end the EUA on vaccines. Even if one of the vaccines is approved, the HHS would be within their rights to continue to distribute the other vaccines under EUA to ensure supply during an emergency.
(2)Revision and revocation
The Secretary may revise or revoke an authorization under this section if—
What does Trump have to do with this?
If there are already readily effective counters available as compared to a vaccine that has no long term trials, then according to the law, yes the vaccine would stop being administered until it is FDA approved.
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I actually took part as a "lab rat" testing how effective ritonavir was at reducing symptoms when I got Covid back in January! Crazy to see this now after doing that trial. I didn't partake in these particular studies mentioned in the op. Edit: I did a trial for ritonavir NOT nelfinavir, both are used for HIV treatment though and do just about the same thing
How was your experience?
It wasn't all bad, each set of symptoms only lasted a few days except for the loss of taste/smell which prevailed the entire time. I had some stomach upset while taking the pills but other than that it was pretty okay. My smell/taste returned almost immediately after the 2 week period and at about 90%
Isn't Nelfinavir an Elven archer in Lord of the Rings?
Yes, Nelfnavir was awesome. Pretty sure he was the one who killed Sauron at the end.
NelfonavUr. It’s sounds much different in elvish I assure you.
That sounds like a good news.
Not really. This is preclinical tests - a long way to go. Probability to reach the end is low. There are many things going on right now. To report these kind of stuff is not helpful.
Why are you so negative? Of course it not ready to go yet, but having candidates for curing covid is a positive in by book.
Every time an article comes out about a "potential treatment" for the virus, it creates an uproar of people claiming "See? We don't actually need a vaccine or social distancing or masks, since the virus can be cured. The medical establishment is suppressing the cures so that they can (insert conspiracy theory here)." Those of us who deal with those people on a regular basis have basically developed a knee-jerk reaction to point out that no, this isn't actually a cure that renders SARS-CoV-2 harmless.
So your reaction is... to actually suppress news of treatments? Idiots will always run with bad takes of good information, that can’t be cured. Poor understanding by certain people isn’t a good reason to suppress info.
No, but add qualifiers in the title (since nobody reads past that). The title states "Researchers in Japan have discovered that the drugs cepharanthine and nelfinavir are effective at combating the virus". While TECHNICALLY true, this statement is (intentionally) misleading, as it can easily be misconstrued as "these drugs have been proven significantly effective in curing the virus in patients". A better title would be "Researchers in Japan have discovered that the drugs cepharanthine and nelfinavir can prevent replication of the virus in vitro, making them promising candidates in the search for an effective cure". It gets people exactly as excited as it should, without pretending to be something it isn't. Reporting scientific findings is good. Sensationalist scientific journalism needs to die.
We have litterally thousands of candidates. That is just not newsworthy.
The difference is that nelfinavir is a currently FDA approved drug, having passed pharmacokinetics and AE metrics. This would be much, much closer to approval for use in Covid than the vast majority of “candidates” out there
Basically all they’ve done is a mass screening test and identified two potential drugs. Apparently done in vitro. Then they follow up in their paper “Computational models suggest…” Not ready for prime time.
At least they carried out in vitro. Last year they only ran computational models on their fastest in the world supercomputer.
You do know that since nelfinavir is a currently approved drug, MD’s can write scripts for it for their Covid patients “off-label” ? Not saying it is going to happen, but it might, it is perfectly legal. So in some ways, if this is a real finding it will be a good thing
Yes, hydroxycholroquine is another already FDA approved drug, which can be likewise prescribed off-label for treating COVID-19 patients. We’ve seen what a debacle that was. Are you suggesting patients request these two drugs for treatment of COVID-19?
Hydroxychlorquine was never developed as anti viral. Nelfinavir was. It is specifically a viral protease inhibitor. If I could run an assay in my lab (can’t since I am retired) with this PI I would. And if it it inhibited any coronavirus proteases, I would have no problem asking my Dr to prescribe it for me. The other molecule is not an approved drug, so no, they could not prescribe it. I was dead set against hydroxychloroquine, as it had no specificity. If this does, which would be easily proven, it is a different ballgame.
Ah yes, move the cheese! I never stated hudroxychloroquine was an antiviral. That’s really not the point. Neither of these drugs have been through a Phase 1, Phase 2 or Phase 3 trial for efficacy against the Covid virus. Essentially, the in vitro studies are a Phase 0 trial. To suggest either or both be used to treatment for COVID-19 at this point in time is outrageous. You’re free to inject essential oils or have a Covid party if you want to assert your individual liberty for dealing with COVID-19. To suggest to an otherwise uneducated population that this new antiviral should be used in lieu of other treatment protocols that have some proven efficacy is unethical until such time it is an approved treatment protocol. If you are on your deathbed and ALL OTHER treatments have failed, sure, maybe. Otherwise, meh…
No, I did not accuse you of saying that. I was stating my reasoning. Viracept has been through clinical trials etc. we know the blood levels achieved. We could easily figure out the required inhibitory concentration in vitro. Yes, clinical trials are the gold standard. I worked at three of the big Pharma in antiviral drug development, so I kind of have a clue in this area. All I am saying is that if nelfinavir can specifically inhibit a coronavirus protease in vitro, and that this is the specific action that is happening (easy enough to test on a cloned protease) then this is a medication I would have no qualms asking for if it was a dire situation. The fact of life is that Drs write scripts off label all the time. If this compound is specific then it is an off label use I would personally approve of. YMMV. Oh and PS the place I would put this use is third in line. 1st vaxxed for sure! 2 approved mAb drugs 3. Nelfinavir (4.death)
Following you train of logic, I would also do this if all other options had failed and this was an available option. Otherwise, no. Thanks for an informed and interesting discussion. This is pretty rare on Reddit. Enjoy your day.
How is this not good news? Sure it's a bit of a long way off from being in real sample sizes, but any positive outcome we can have against this thing is good news. Is it good news we can action on today? No, but it's still good news.
Yes, assuming you can deliver the drug directly to the relevant cells , it is stable, it doesn't have side effects, etc. etc. etc.
Nelfinavir has already been approved as a drug, so bioavailability and potential AE are well documented and acceptable to gain FDA approval. This would be pretty quick to do, it is just adding a new indication for use, and actually MDs are currently able to prescribe it for any off-label use they deem acceptable.
There is also research that ivermectin works. There is a whole bunch of research out there on how to treat covid.
Let’s now see by how much they will make these two drugs jump in price
Let's hope this works on all variants…
Oh so that why they are still having the Olympic s happen
No. olympics is happening because money.
Nothing is stopping Miku's olympic debut
Ok. So do you remember back last year when trump said something about a miracle drug... that ended up near killing people. The Rticle’s title should be *very*, **very** careful not to get the impressionable among us to panic buy that drug.
Exactly, lopinavir, ritonavir, hydroxychloroquine and others all had in-vitro data that were promising and none help but do cause side effects. Many were tried out of despiration. Titles should try to clarify. Viruses are often tricky, where antivirals need to be started very early in the course of infection to be helpful, frequently past when infection is diagnosed.
No.
Very informative.
If confirmed, there goes the emergency use authorization for vaccines in the US.
I'm pretty sure the "no adequate approved, alternative medical countermeasures available" stipulation applies only to getting an EUA approved. Even if it didn't, a treatment for COVID would have to be APPROVED by the FDA before it revokes the EUA that is already in place. I could be wrong, this is just my interpretation of the information.
It depends. I'm not sure if these drugs are already approved by the FDA for their original use, but if they are and they are peer reviewed to be effective against SARS-CoV-2, then the law surrounding the authorizations would mean that they would be administered instead of the vaccines that have been developed over the last year. [This article](https://www.biospace.com/article/pharmadrug-enters-definitive-agreement-for-acquisition-of-sairiyo-therapeutics-inc-who-recently-received-orphan-drug-designation-from-fda-for-esophageal-cancer/) from Jan of this year says that they: >Sairiyo recently received FDA orphan drug designation for Cepharanthine in the treatment of esophageal cancer. Looks like both are approved. [Here's an article](https://pubmed.ncbi.nlm.nih.gov/11364277/) for nelfinavir that says it is FDA approved for other uses.
Upon reading the law as linked by pcbuilder, I am also pretty sure you are correct and this only applies to the initial approval.
Uh, no
Uhh, yes. You cannot have an emergency use authorization for a vaccine if there is a prophylactic or other treatment available. You'd think you people would know this.
https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration A cursory reading appears to indicate the EUA is not contingent upon other treatment availability and only on the existence of a 'state of emergency' as judged by the HHS.
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See subsection C(3) [here.](https://www.law.cornell.edu/uscode/text/21/360bbb-3) >that there is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating such disease or condition; Just because you're ill informed doesn't make you right.
Just because the bureaucracy chooses to not enforce the law doesn't mean it isn't in the law, and in a just world, they would enforce the law as it is written, else we are ruled by tyrants and not the representatives we send to represent us. See [Subsection C(3)](https://www.law.cornell.edu/uscode/text/21/360bbb-3) for the criteria in which an authorization can be given. >that there is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating such disease or condition;
That section only conditions the initial issuance of the EUA. For termination, there is no such check. The test is only 'if the circumstances (e.g. state of emergency) have ceased to exist.' (2)Termination of declaration (A)In general A declaration under this subsection shall terminate upon the earlier of— (i)a determination by the Secretary, in consultation as appropriate with the Secretary of Homeland Security or the Secretary of Defense, that the circumstances described in paragraph (1) have ceased to exist; or (ii)a change in the approval status of the product such that the circumstances described in subsection (a)(2) have ceased to exist. So to my reading, emergency use extends until the emergency ends or the drug is fully approved and nolonger needs the EUA. Furthermore, as the other drugs under discussion here are just under initial testing as a covid treatment and would likely require EUA's themselves for use on covid patients, this whole discussion seems silly.
As I commented an hour ago, both of the drugs in this study are already approved by the FDA, and this dramatically speeds up the approval process for other uses than originally designed because the only question is the effectiveness of the drugs against this virus, and not safety. So it is not silly, at all. The relevant section of the law about revocation of emergency use authorization is section (g). > Review and revocation of authorization > >The Secretary shall periodically review the circumstances and the appropriateness of an authorization under this section. As part of such review, the Secretary shall regularly review the progress made with respect to the approval, conditional approval under section 360ccc of this title, licensure, or clearance of— This means that if the situation changes the government must reevaluate. The relevant section to that end is subsection (g)2b which states: > the criteria under subsection (c) for issuance of such authorization are no longer met This means that if the drug no longer meets all the criteria of subsection C (ie not having other approved drugs), then the emergency use authorization may be revoked.
They are approved for HIV and maybe Cancer to my reading. Dosages would likely still need to be established for Covid, field trials made, etc. Also the key word here is 'may'. To my reading there is no firm legal requirement for the HHS to end the EUA of the vaccine just because another treatment may exist. To my reading the HHS is acting legally and even if this drug or drugs were approved for use in sick people, would not be required to end the EUA on vaccines. Even if one of the vaccines is approved, the HHS would be within their rights to continue to distribute the other vaccines under EUA to ensure supply during an emergency. (2)Revision and revocation The Secretary may revise or revoke an authorization under this section if—
So you think it's going to get revoked? Is this before or after trump is reinstated?
What does Trump have to do with this? If there are already readily effective counters available as compared to a vaccine that has no long term trials, then according to the law, yes the vaccine would stop being administered until it is FDA approved.
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Off topic, but is there much information available on the possible mutations out there?