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COVID-19 antivirals and vaccines (Megathread)

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26 minutes ago, Kartazion said:

This means that covid-19 can make a viral rebound and be reactivated in the case of a person who is already a carrier. 
The vaccine won't provide a solution if the virus is hiding. The vaccine will only be effective if the person has never had the virus, right?

No, if one is infected but e.g. with such a low amount that the body did not build up memory, a vaccine that triggers a stronger response can be beneficial. However, a person that has been exposed to sufficient viruses and/or vaccine would mount a faster and stronger response once the virus pops up again and thereby have a higher likelihood to clear the virus before it actually manages to go into hiding. 

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5 hours ago, CharonY said:

However, a person that has been exposed to sufficient viruses and/or vaccine would mount a faster and stronger response once the virus pops up again and thereby have a higher likelihood to clear the virus before it actually manages to go into hiding

That hidden viruses of the immunity could constitute a viral reservoir, and the immune defense no longer reach viruses.
This viral reactivation is a possibility still under investigation.

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There was a paper circulating a little while ago that caught my attention, published in Nature. 

https://www.nature.com/articles/s41586-020-2223-y

To be honest, I am pretty baffled that it was published in Nature. The top leads identified in their screening assay are known as pan-assay interference compounds (PAINs). IOW, they are nuisance compounds and generally not something you would pursue in a drug design campaign. In fact, the seminal paper that discusses PAINs is a Nature paper (https://www.nature.com/news/chemistry-chemical-con-artists-foil-drug-discovery-1.15991), which makes this even more confusing. I can't imagine anyone with a med chem background would have reviewed this, as the red flags should have been very obvious. In any med chem journal, this paper would have been rejected since you have to screen for PAINs as part of their submission guidelines. I'm worried that this signals a general lowering of the bar when it comes to these sorts of publications, which will only make things more difficult in the long run. Derek Lowe has written some good blog posts on the matter:

https://blogs.sciencemag.org/pipeline/archives/2020/04/10/more-on-screening-for-coronavirus-therapies

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It does look like that they may not have found the right reviewers. Often reviews are long and iterative in nature and I don't think they are good for these fast turnaround papers where we have to assume a lower certainty.

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19 hours ago, BabcockHall said:

https://www.statnews.com/2020/04/29/gilead-says-critical-study-of-covid-19-drug-shows-patients-are-responding-to-treatment/

Patients taking remdesivir recovered more quickly than those taking a placebo.  Business Insider and CNN have stories.

It makes sense, because remdesivir has been useful against other coronaviruses, SARS so far as I recall, or was it Ebola. Also because the molecule is similar to adenosine and seems able to trick a viral RNA polymerase to try to build it into new RNA strings where adenosine would have belonged, and thus blocking the further production of the viral RNA.

On the other hand, the link states that "Gilead says", and Gilead is a (the?) manufacturer of remdesivir in the US. The available information about the study says that the decrease in lethality among test patients treated with remdesivir was not statistically significant (the shorter recovery times presumably were?)  compared to the patients treated with placebo. And an earlier study of the same drug did not produce any determination. So maybe more tests are needed.

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It has been employed against different viral diseases, incl. SARS, MERS Ebola and a few others. Don't recall respective efficacy, though.

You are also correct that recovery time was the major effect.

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If this was already discussed on SFN, please direct me...

Here in eastern europe, there is some speculation that the reason why eastern europe seems less affected by covid-19 (in comparison to the western europe) could be due to previous vaccination against tuberculosis (the BCG vaccine). This seems far fetched to me, but what is your opinion?

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Posted (edited)
8 minutes ago, Danijel Gorupec said:

If this was already discussed on SFN, please direct me...

Here in eastern europe, there is some speculation that the reason why eastern europe seems less affected by covid-19 (in comparison to the western europe) could be due to previous vaccination against tuberculosis (the BCG vaccine). This seems far fetched to me, but what is your opinion?

Is there any evidence that BCG vaccination was more common in Eastern European countries? It was still routine in the UK until very recently, as far as I know.

Even if it is not routine now, it certainly was in the past and so we would expect to see older people less likely to have serious Covid-19 infections, but that is actually the opposite of what we see.

 

Form the WHO:

Quote

There is no evidence that the Bacille Calmette-Guérin vaccine (BCG) protects people against infection with COVID-19 virus. Two clinical trials addressing this question are underway, and WHO will evaluate the evidence when it is available. In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19. WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis.

https://www.who.int/news-room/commentaries/detail/bacille-calmette-guérin-(bcg)-vaccination-and-covid-19

Edited by Strange

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2 minutes ago, Strange said:

Is there any evidence that BCG vaccination was more common in Eastern European countries? It was still routine in the UK until very recently, as far as I know.

This is what proponents of this idea are pointing out - allegedly, the BCG vaccination is still obligatory in eastern Europe for all children, while is not obligatory in western europe (Portugal being an exception). I didn't check these claims... If UK still has a large portion of population BCG vaccinated, as you suggest, then the idea just falls apart.

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I suspect an easier explanation is a mix of volume of travel from infected areas and potentially incomplete testing. In Russia the number of detected cases are rising rapidly.

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It should be noted that the drug is a steroid, which are used to manage inflammation and are not antivirals.

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On 4/16/2020 at 8:22 PM, hypervalent_iodine said:

There was a paper circulating a little while ago that caught my attention, published in Nature. 

https://www.nature.com/articles/s41586-020-2223-y

To be honest, I am pretty baffled that it was published in Nature. The top leads identified in their screening assay are known as pan-assay interference compounds (PAINs). IOW, they are nuisance compounds and generally not something you would pursue in a drug design campaign. In fact, the seminal paper that discusses PAINs is a Nature paper (https://www.nature.com/news/chemistry-chemical-con-artists-foil-drug-discovery-1.15991), which makes this even more confusing. I can't imagine anyone with a med chem background would have reviewed this, as the red flags should have been very obvious. In any med chem journal, this paper would have been rejected since you have to screen for PAINs as part of their submission guidelines. I'm worried that this signals a general lowering of the bar when it comes to these sorts of publications, which will only make things more difficult in the long run. Derek Lowe has written some good blog posts on the matter:

https://blogs.sciencemag.org/pipeline/archives/2020/04/10/more-on-screening-for-coronavirus-therapies

Duck, duck, duck, duck, homodimer!!!!


 How many months until the vaccine can be approved for widespread use, again?  We might already be immune by that time if they don't disseminate this information carefully.

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24 minutes ago, MonDie said:

Duck, duck, duck, duck, homodimer!!!!

 


 How many months until the vaccine can be approved for widespread use, again?  We might already be immune by that time if they don't disseminate this information carefully.

It would fall until the emergency approval pipeline. Herd immunity would take at least another year according to projections, assuming there are no further restrictions.

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Accumulating evidence suggests anti-TNF therapy needs to be given trial priority in COVID-19 treatment https://www.thelancet.com/.../PIIS2665-9913(20.../fulltext

An inflammatory cytokine signature predicts COVID-19 severity and survival..We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. https://www.nature.com/articles/s41591-020-1051-9

Patent, papaya leaf extract as tnf-alpha inhibitor
https://patents.google.com/patent/US20140065251

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