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Michael Lin, PhD-MD 🧬 Profile picture
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22 Dec, 5 tweets, 2 min read
I've been meaning to reveal some exciting results from my lab's SARSCoV2 protease inhibitor research. With FDA approval of Pfizer's Paxlovid today, it's a good time to finally share our good news as well.

We've developed not 1 but 2 inhibitors with activity superior to Paxlovid.
This work began in March 2020 when we hypothesized the HCV protease inhibitor boceprevir could serve as a template for the creation of orally dosable SARSCoV2 protease inhibitors. We announced initial results from this work in September 2020.
Our initial drug, ML1000, described in 2020 September, preceded Pfizer's PF-07321332 (Paxlovid) announced in 2021 April and approved today. Other groups have also made drugs with boceprevir parts, but our drug is the closest in structure to PF-07321332
Our two best drugs, ML1006a and ML1006SN, derive from ML1000 as well, and are thus siblings of Paxlovid. We are working on even further improvements while we discuss commercialization possibilities.
I'll come back with more info in the future but the thread below explains our drug development process. It is a story of being prepared for serendipity

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More from @michaelzlin

Michael Lin, PhD-MD 🧬 Profile picture
23 Dec
Would you prefer (1) we get back to normal activities sometime, or (2) we make new vaccine-evading coronaviruses continuously, suffer widespread breakthrough waves, and wear masks forever?

If you chose #1, then know this: Merck's molnupiravir should not be approved.
Molnupiravir is, to put it in clear terms, a potentially dangerous and virus-enhancing drug. It is not an effective antiviral medication outside of the confined conditions of cell culture and hamster cages. I'll explain below.
Well known independent voices have brought this up, such as @CT_Bergstrom (renowned skeptic of bad research) @WmHaseltine (HIV pioneer) and @JamesEKHildreth (FDA advisor). Others such as @chasewnelson have done more in-depth analysis. I'm here to try to explain the issue simply.
Read 72 tweets
Michael Lin, PhD-MD 🧬 Profile picture
22 Dec
👍🙂💊SARSCoV2 protease inhibitor Paxlovid approved as the first pill for preventing severe COVID19 i the US.

This is great news, as it prevents hospitalizations by 89% in high-risk patients with SARSCoV2 infections.

And I'm obligated to point out that we were the first to invent a SARSCoV2 protease inhibitor with the essential elements later found in Paxlovid (we showed our drugs in 9/2020, Pfizer announced Paxlovid in 4/2021)
It's commonly misreported that Pfizer was able to make Paxlovid quickly because they had SARSCoV1 protease inhibitors from 2005. That is absolutely false. Paxlovid did not derive from their prior work. It was derived from our or other labs' work in 2020.
Read 10 tweets
Michael Lin, PhD-MD 🧬 Profile picture
17 Dec
Finally, what we've been waiting for: age-controlled data on Omicron severity, courtesy SA health ministry.

Across all ages, deaths among hospitalized pts are 2/3 lower in Omicron wave.

If more mild cases are admitted, this # goes down, but doesn't seem likely that's the reason Image
Source:

h/t @b_chinnian5
@b_chinnian5 Importantly, they said the vast majority of hospitalized cases were unvaccinated. But SA has a high rate of seroprevalance, >70% per some studies. So worst-case interpretation here is everyone hospitalized was either vaccinated or unvaccinated but previously infected.
Read 33 tweets
Michael Lin, PhD-MD 🧬 Profile picture
17 Dec
Meta-thread (trying to keep tweets organized by topic)

2020.03: The #coronadeck, in which I explained that we knew a lot about SARSCoV2 because it's 80% identical to SARSCoV1. Discussed evidence for the usefulness of masks, previewed possible Rx, etc

2020.04: Why SARSCoV2 disease should have been called simply SARS2 or vSARS or even simply SARS, rather than the meaningless COVID-19.

2020.07: Proposing that preadolescent children should be considered separately from adolescents, and hypothesizing that they may have milder disease because of stronger innate immunity.

Read 19 tweets
Michael Lin, PhD-MD 🧬 Profile picture
14 Dec
An important study just posted from @BalazsLab

Findings are good for Pfizerites and Modernans but sobering for #JnJers

#JnJers even after boosting have lower neutralizing antibodies against Delta and Omicron vs 3x Pfizer

I'll discuss implications

🧵

Study design is excellent. Relevant vaccine statuses were tested in parallel: {Moderna, Pfizer, J&J} x {distant vax, recent vax, infection+vax, boosted vax}. Assay was pseudovirus neutralization. Color-coded images explain everything.
Also there's a very informative diagram of what was actually done. A picture not just says 1000 words, but is so much easier to understand and prevents confusion about what reagents and procedures were used, so hoping this becomes more common in papers.
Read 30 tweets
Michael Lin, PhD-MD 🧬 Profile picture
13 Dec
ICYMI: Another reason not to take #molnupiravir is mutagenesis of the patient DNA hasn't been ruled out.

We've already ruled *in* viral mutagenesis.

The push to approve molnupiravir feels like Challenger-style "go fever".

Sanity needs to prevail.

nytimes.com/2021/12/13/hea…
When we discovered boceprevir has activity against SARSCoV2, we contacted Merck and let them know, because it was their drug and we figured they could modify the compound for even better activity.

Boceprevir activity below, also published by others.
biorxiv.org/content/10.110…
Well Merck didn't pursue a boceprevir derivative for COVID19, and chose instead to bet on a new drug that creates mutations in the virus as its only mechanism of action. This had never been tried before (there's a belief ribavirin does, but it has other inhibitory effects).
Read 8 tweets

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