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s_r_constantin's profile
Sarah Constantin
Sarah Constantin
Sarah Constantin
@s_r_constantin

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Sarah Constantin

@s_r_constantin

Math/ML/data-science person now working on solving aging...and helping with COVID19?! Founder, LRI and Daphnia Labs. Married to @oscredwin

Be
srconstantin.posthaven.com
Joined February 2019

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    1. ice9‏ @__ice9 Apr 15
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      ice9 Retweeted Anand Ranganathan

      Two more in vitro antivirals, but unfortunately both likely useless. Even assuming 100% bioavailability and uniform tissue distribution, the highest typical therapeutic doses of each would be 10x too low to hit even the IC50. Retrospective benefits likely just antihypertensive.https://twitter.com/ARanganathan72/status/1250351925293273088 …

      ice9 added,

      Anand RanganathanVerified account @ARanganathan72
      Must-read paper published today (non-peer-reviewed) reports BP medicines Benidipine and Amlodipine potently kill SARS-CoV-2 in vitro. Retrospective analysis of CoVID-19 patients on these drugs points to their faster recovery and reduced morbidity. https://www.medrxiv.org/content/10.1101/2020.04.08.20047134v1.full.pdf … pic.twitter.com/ms1DOzrOq9
      Show this thread
      6 replies 6 retweets 33 likes
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    2. ice9‏ @__ice9 Apr 15
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      ice9 Retweeted Trevor Sutcliffe

      Note they may still have helpful _antihypertensive_ effects. I merely mean that these apparent antiviral properties are irrelevant at therapeutic concentrations. See, e.g.:https://twitter.com/TrevorSutcliffe/status/1250367608605401089?s=20 …

      ice9 added,

      Trevor Sutcliffe @TrevorSutcliffe
      Replying to @TrevorSutcliffe @C_Pohlmann
      "efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism"
      2 replies 0 retweets 8 likes
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    3. Sarah Constantin‏ @s_r_constantin Apr 15
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      Replying to @__ice9

      how do you find out for all of these in vitro studies what a therapeutic concentration is? just look them up separately?

      1 reply 0 retweets 3 likes
    4. StopYourLimits‏ @limits_stop Apr 15
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      Replying to @s_r_constantin @__ice9

      Please, answer @s_r_constantin's question. I am most interested on that.

      1 reply 0 retweets 1 like
    5. ice9‏ @__ice9 Apr 15
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      Replying to @limits_stop @s_r_constantin

      Yes. I have collections of papers for in vitro results against SARS-CoV-2, as well as SARS-CoV, MERS-CoV, some of the weaker human CoVs, and animal CoVs. The high throughput screening studies are the most useful, short of dedicated compound-specific investigations.

      1 reply 0 retweets 1 like
      Sarah Constantin‏ @s_r_constantin Apr 15
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      Replying to @__ice9 @limits_stop

      me too, but most of these are repurposed drugs for other uses. i'm just asking about your process. (I could of course make my own spreadsheet & try to convert the therapeutic dose in humans to an in-vitro equivalent? but too lazy rn).

      10:42 AM - 15 Apr 2020
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      • Adam Strandberg
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        2. ice9‏ @__ice9 Apr 15
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          Replying to @s_r_constantin @limits_stop

          Yes, I did a thread on new candidates as well a little while ago, but they have more potential safety risks.... Also relative concentrations for related CoVs tend to be off somewhat relative to SARS-CoV-2, so I try to get direct confirmation. SARS-CoV usually +/-50% though.

          2 replies 0 retweets 1 like
        3. ice9‏ @__ice9 Apr 15
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          Replying to @__ice9 @s_r_constantin @limits_stop

          For dose estimation from in vitro IC50/IC90, an *optimistic* guess starts at: g/mol * IC50(/90) mol/L * 50-70L / bioavail This usually undershoots actual pharmacokinetics a bit. Specific papers on pharmacokinetics (esp. tissue specific) better if can be located.

          1 reply 1 retweet 3 likes
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