Here’s another post that I will regret writing, but a great many people have asked me about a new preprint that brings up the possibility of antibody-dependent enhancement with the current vaccines and the Delta variant. To be frank, some of the people promoting this seem to be r … | Continue reading
When we last checked in with the Klapötke lab at Munich, it was to highlight their accomplishments in the field of nitrotetrazole oxides. Never forget, the biggest accomplishment in such work is not blowing out the lab windows. We’re talking high-nitrogen compounds here (a specia … | Continue reading
The current pandemic has made everyone think a lot more about viruses than they ever had any desire to, but they’re a constant background to our lives – and to the lives of pretty much every living creature. Humans have their viruses, other mammals have theirs (with occasional ca … | Continue reading
Now this is a paper that’ll make your head spin. It’s from the Zhu group at Tsinghua University, and the head-spinning will be both because of the subject matter and the amount of work involved. So let’s get chiral – first, a bit of background for readers who don’t think about th … | Continue reading
The latest addition to the long list of chemicals that I never hope to encounter takes us back to the wonderful world of fluorine chemistry. I’m always struck by how much work has taken place in that field, how long ago some of it was first done, and how many violently hideous co … | Continue reading
I enjoyed this Twitter thread very much from “Bob the Grumpy Med Chemist”. It leads off with a document that pops up periodically on the internet, a guide to sabotage that was put out by the OSS (precursor to the CIA) during the second World War. Along with practical suggestions … | Continue reading
I don’t do a lot of posts on plant biochemistry here, but this news is pretty notable, and it illustrates several points that apply across other fields as well. This new paper has as its background the role of a particular methyl group in the structure of RNA molecules: N6-methyl … | Continue reading
Here’s a new paper with a surprise: a small molecule that appears to be very effective against malaria, with what may be a high barrier to developing resistance (C&E News coverage here). It’s from a large multicenter (multicontinent) team, and the chemical matter has its origins … | Continue reading
New ideas about intelligence rocked the nascent field of academic psychology in the 1930s | Continue reading
I last wrote about Deepmind’s efforts to predict protein folding and structure here, with their AlphaFold software. AlphaFold really performed very strongly in the 2020 protein folding challenge, and that got a lot of attention. Well, they’ve recently published a great deal of de … | Continue reading
I last wrote about Deepmind’s efforts to predict protein folding and structure here, with their AlphaFold software. AlphaFold really performed very strongly in the 2020 protein folding challenge, and that got a lot of attention. Well, they’ve recently published a great deal of de … | Continue reading
Back last summer, I was writing blog posts about possible side effects of mass vaccination. For readers who’ve shown up more recently and might have me filed as Defender of Vaccines, that might seem surprising, but remember, I’ve been in drug discovery for a long time now. All dr … | Continue reading
Here’s some surprising information to learn about a drug that’s been around for decades. Temozolomide (TMZ) is a chemotherapy agent, used in several intractable conditions such as glioblastoma. It’s pretty vicious stuff – the mechanism is through alkylation of guanine residues in … | Continue reading
I would like to recommend this piece at Stat about the details of the Biogen aducanumab approval. It’s behind the paywall, but it’s a deeply reported piece from Adam Feuerstein, Matthew Herper, and Damian Garde about how in 2019 Biogen launched an effort to get their apparently f … | Continue reading
The huge success of the mRNA vaccination platform during the pandemic has set a lot of people to thinking about what comes next. Moderna and BioNTech, of course, have been thinking this way for quite some time. But Sanofi now says that they’ll be investing large amounts into the … | Continue reading
In many parts of the US, things are returning to normal thanks to the steep drop in coronavirus cases, which in itself is very likely due to a combination of vaccination and warmer outdoor weather. I very much hope that we can continue this process on into the fall under the thre … | Continue reading
Here’s a new paper (open access) from a large multi-center team of authors urging caution on many of the reports of small-molecule repurposing screens against coronavirus activity. The list of drugs that has shown activity in vitro is long, and the list of potential targets is as … | Continue reading
1. Novavax Clinical Data Word came yesterday that Novavax had very good safety and efficacy in the trial of their recombinant protein vaccine. This is good news. By this point, the vaccine is much less needed here in the US, but it could be a very important part of getting many o … | Continue reading
I wasn’t planning on having this turn into Coronavirus Vaccine Week again around here, but we do have some news. Yesterday afternoon CureVac, the German mRNA vaccine company, reported results of their Phase III trial in 40,000 patients around the world. They weren’t good. And the … | Continue reading
I last wrote about ivermectin here, but I’m getting so many question about it that I need to revisit the topic. Although (I’ve said this before), I believe that I will regret doing it, because I expect the signal/noise in the comments section to degenerate to mid-pandemic levels … | Continue reading
As the world knows, the FDA approved Biogen’s anti-amyloid antibody today, surely the first marketed drug whose Phase III trial was stopped for futility. I think this is one of the worst FDA decisions I have ever seen, because – like the advisory committee that reviewed the appli … | Continue reading
Cadmium is bad news. Lead and mercury get all the press, but cadmium is just as foul, even if far fewer people encounter it. Never in my career have I had any occasion to use any, and I like it that way. There was an organocadmium reaction in my textbook when I took sophomore org … | Continue reading
This is an excellent overview at Stat on the current problems with machine learning in healthcare. It's a very hot topic indeed, and has been for some time. There has especially been a flood of manuscripts during the pandemic, applying ML/AI techniques to all sorts of coronavirus … | Continue reading
There's some really interesting CRISPR news out today, and it's likely to be a forerunner of much more news to come. A research team has demonstrated what looks like robust, long-lasting effects in a primate model after one injection of the CRISPR enzymatic machinery. There have … | Continue reading
The announcement by the Biden administration about waiving IP rights to the coronavirus vaccines obviously calls for some comment. Keep in mind that I have been doing research in the pharma industry for over 30 years now, so my viewpoint is obviously going to be affected by that, … | Continue reading
The announcement by the Biden administration about waiving IP rights to the coronavirus vaccines obviously calls for some comment. Keep in mind that I have been doing research in the pharma industry for over 30 years now, so my viewpoint is obviously going to be affected by that, … | Continue reading
I've been getting a lot of questions in the last few days about several Spike-protein-related (and vaccine-related) topics, so I thought this would be a good time to go into them. There's been a recent report about the vascular effects of the Spike protein alone (not coronavirus … | Continue reading
We have two pieces of news about the Gamaleya Institute's "Sputnik-V" vaccine today. Neither of them are going to be enjoyable to go into.First off, many may have heard that the Brazilian regulatory authorities had a hearing yesterday to see if this vaccine would be approved for … | Continue reading
Excellent news today: we have word of the most effective malaria vaccine yet discovered. A year-long trial in Burkina Faso has shown 77% efficacy, which is by far the record, and which opens the way to potentially relieving a nearly incalculable burden of disease and human suffer … | Continue reading
The New York Times has a good story on the problems at the Emergent vaccine plant in Baltimore, following up on this one. They've uncovered a report from last summer that warned that the facility had quality control problems:A copy of the official’s assessment, obtained by The Ne … | Continue reading
The final implosion of the Stemcentrx deal is worth a note, although I said a lot of what I have to say about it back in December. I want to especially emphasize two points I made back then - first, that the failure of this whole acquisition is different only in degree, and not i … | Continue reading
I've been meaning to write some more about artificial intelligence, machine learning, and drug discovery, and this paper (open access) by Andreas Bender is an excellent starting point. I'm going to be talking in fairly general terms here, but for practitioners in the field, I can … | Continue reading
Everyone will have heard of the situation in Europe right now, with a whole list of countries suspending dosing of the AstraZeneca/Oxford vaccine. Sweden and Latvia joined that list today .But getting clarity on this is another thing entirely.I have not been the biggest fan of th … | Continue reading
I've had several questions about antibody-dependent enhancement, which has always been a worry as the coronavirus vaccines have been developed. I figured it might be worth a look at just what we know about it, why one might be worried, and why (on the other hand) one might be hop … | Continue reading
There's a report of an interesting small-molecule drug effort against the coronavirus that seems to have produced rather significant results. The idea goes back to effects that were noticed last year - for example, in this population-based study from Italy. It's been known since … | Continue reading
In my experience, most organic and medicinal chemists are always ready to hear about the latest results in two branches of the science: things that explode and things with weird smells. Maybe we are in our way "singularly in touch with the primitive promptings of humanity", as Ca … | Continue reading
Fifty years ago, the blockbuster du jour was The Andromeda Strain, a film based on a new kind of biomedical thriller that depicted a plague of putatively extraterrestrial origins. The film—directed, perhaps incongruously, by Robert Wise of The Sound of Music fame—would in time be … | Continue reading
This story has been passed around a lot the last few days, and I've had several people ask me what I've thought of it. It's on a really interesting possibility for a malaria vaccine, and part of the narrative hook is that it's using mRNA technology, which is about as attention-ge … | Continue reading
Over the years I've very much enjoyed being startled by the scientific literature, and there haven't been many times when I've been more surprised than I was this morning. I've been making references on this blog for years about how we don't even know how antidepressants work, bu … | Continue reading
The other day I had a look at the process used to make the mRNA vaccines, so I thought it would be a good idea to do the same for the adenovirus vector ones, such as J&J, Oxford/AstraZeneca, CanSino, Gamaleya et al. It's a different system, with its own advantages and disadvantag … | Continue reading
In the last few days, the question of why more drug companies haven't been enlisted for vaccine production has come up. It's mostly due to this tweet:The problem is, as far as I can see, this is simply wrong. There are not "dozens of other pharma companies" who "stand ready" to p … | Continue reading
We're definitely not out of the pandemic woods yet, and neither is this blog - so let's talk some more about antibodies today, in the hopes that we're getting closer to the time when I (and all of us) can ignore immunology for a while.But we're not ignoring it today! There's a lo … | Continue reading
A question that comes up a lot about mRNA vaccines is what happens at the cellular level after you're injected with one. The mechanism of any such vaccine is to cause cells to produce a viral protein antigen, but which cells actually do this? It's also understood that mRNA vaccin … | Continue reading
This new article, I have to say, is rather reassuring about the human immune response to the coronavirus. It's from a large team centered at Rockefeller University in New York, and it examines 87 people who have previously been infected. We've seen many studies of antibody titers … | Continue reading
There's been a lot of news, so it's time to survey the vaccine landscape. For this post, I'm only going to cover the big players that are either deep into human trials or have actually been rolling out vaccines to the general population - another post to come will go further down … | Continue reading
OK, time to write about the topic that's been the talk of the coronavirus world the last day or two: the new strain that has been detected in the UK. I'll go ahead and put the bottom line right here, and then go into the details: I'm not sounding any alarm bells, but this does be … | Continue reading
For people looking for an accessible writeup on the coronavirus mutational landscape, I can recommend this Reuters article that came out today. It has a lot of good information in it, and a lot of very well-made graphics to show what's going on. Past blog posts on this subject ar … | Continue reading
This weekend brought some really significant news in the long-running effort to use gene editing to treat human disease. As most readers will have heard, Boston Children's Hospital and a Vertex/CRISPR effort both published papers in the NEJM addressing sickle-cell anemia and beta … | Continue reading