Lawrence 🧑‍💻🦠

Husband, papa, Google PM working on Agents and GenAI. Views are my own.

[unusual_whales @unusual_whales]

FOMC is tomorrow.

Will the Fed hike rates?

Listen to the experts, including:

@josephwang
@super_macro
@stevehou

Come join Wednesday at 12:55PM EST:
https://t.co/AbLm1NfMSw

[Lawrence 🧑‍💻🦠 @that_lawrence]

@danaparish @LauraMiers HIV can stay dormant in cells for 10+ years, so it's highly unlikely that 15 days of a viral replication inhibitor would work.

[Lawrence 🧑‍💻🦠 @that_lawrence]

(Explanation without the scientific jargon) Imagine viruses like SARS-CoV-2 as tricky invaders that keep changing their disguises (mutating) and wrap themselves in a kind of camouflage cloak or a sugary "shield" (glycosylation) that hides their vulnerable spots.

Our natural defense system, and the antibody drugs we've developed, often work like highly specific keys designed to fit very precise locks on that invader. This works great for invaders that don't change much.

But when the invader is constantly changing its lock and hiding behind a shield, those specific keys stop working. It's like trying to use the same house key on a door that changes every week!

For a virus like this, which is always shape-shifting and using its sugar shield, focusing only on those specific "key-and-lock" antibodies is incredibly difficult.

Instead, we really need tools that can grab onto the parts of the virus that don't change, no matter what disguise it wears or how thick its shield is. A key area for this is actually that sugary "shield" itself – even though it's complex, there are often underlying patterns and structures within that sugar coat that stay the same.

This is where tools like lectins come in. While antibodies recognize specific protein shapes, lectins are a type of molecule that are really good at recognizing and binding to specific sugar patterns. Think of them as tools that can interact directly with that non-changing sugar coat.

It's also interesting because, much like antibodies, when lectins bind to a target, they can signal our immune system to wake up and attack. So, they are similar to antibodies in their ability to trigger defenses, but they work by recognizing sugars instead of protein shapes.

Ultimately, while traditional antibodies and vaccines are powerful tools, for a rapidly changing, heavily shielded virus like SARS-CoV-2, targeting those non-changing parts – perhaps focusing on conserved structures within the sugar coat using tools like lectins – might be a more effective and lasting way to disarm the invader. It's about choosing the tool best suited to fight this specific type of tricky, changing enemy.

[Lawrence 🧑‍💻🦠 @that_lawrence]

TL;DR: Highly specific antibodies are ill-suited for mutable, glycosylated SARS-CoV-2; pan-variant binders targeting conserved sites, such as mannose-binding lectins for the glycan shield, offer a more effective strategy.

It is a fundamental principle of immunology that antibodies exhibit high specificity for their target epitopes. While this specificity is invaluable in many contexts, it presents significant challenges when confronting a pathogen characterized by a high mutation rate and extensive glycosylation, such as SARS-CoV-2. The rapid emergence of new variants, each with potential alterations to key viral proteins, means that monoclonal antibodies designed against earlier strains may lose efficacy against newer ones.

My view, which I have articulated previously, is that relying solely on highly specific monoclonal antibodies to maintain durable protection against a highly mutagenic and glycosylated pathogen like SARS-CoV-2 is an uphill battle. Each new variant necessitates the development and testing of potentially new antibody cocktails, leading to a reactive rather than proactive approach.

Instead, I believe a more promising avenue for broad and long-lasting protection against SARS-CoV-2 variants lies in the development of pan-variant binding agents. These agents would ideally target highly conserved sites on the virus that are less prone to mutation. The glycan shield, while presenting challenges, also contains conserved structures that could serve as potential targets for such binders. Developing molecules that can effectively engage these conserved glycans, or other invariant epitopes, could offer a more robust solution against future viral evolution.

Let me be clear: I remain a strong proponent of both vaccines and antibody-based therapies. They are powerful tools in our arsenal against infectious diseases. However, it is crucial that we select the most appropriate tools for the specific characteristics of the pathogen we are facing. For a highly variable virus like SARS-CoV-2, focusing research and development efforts on pan-variant strategies that target conserved elements appears to be a more sustainable and effective path forward for therapeutic intervention.

Thank you for considering these thoughts. I am always open to further discussion on this critical topic.

[Steve Campbell @Historian_Steve]

Your periodic reminder that less ice at the Arctic is consistent with a weaker jet stream that allows cold air to drift down into the Great Plains.

The frigid temps you're experiencing happen BECAUSE of a warming planet, not in spite of it.

[Prof. Peter Strachan @ProfStrachan]

Eight things the world must do to avoid the worst of #ClimateCrisis
1. Stop methane emissions
2. Stop deforestation
3. Restore degraded land
4. Change what we eat
5. Go #RenewableEnergy
6. Use energy more efficiently
7. Stop burning #FossilFuels
8. #ActNow https://t.co/8wNURqsLfL