Two New Approaches to Treating COVID-19

There’s a lot of very cool immunology research being done right now in response to the COVID-19 pandemic. Anti-virals and vaccines top the list for many. But there are significant problems with each — anti-virals have not proven to be wonder drugs, offering only modest help for those already seriously ill, and an effective vaccine is still months or years away. Vaccines may have to be tailored to the age and immune status of various groups, just the way flu vaccines are. But there are other ways of thinking about minimizing both mortality (deaths) and morbidity (illnesses).

Coronavirus and cancer hijack the same parts in human cells to spread – and our team identified existing cancer drugs that could fight COVID-19

This is from Nevan Krogan, Professor and Director of Quantitative Biosciences Institute & Senior Investigator at the Gladstone Institutes, University of California, San Francisco

Kinases are proteins found in every cell of our body. There are 518 human kinases, and they act as major control hubs for virtually all processes in the body. They are able to add a small marker – a process called phosphorylation – to other proteins and thus change how, if and when a phosphorylated protein can do its work. Many cancers are caused by overactive kinases leading to uncontrolled cell growth, and drugs that slow kinases down can be highly effective at treating cancer.

Kinases are also fairly easy to target with drugs because of how they add phosphorylation markers to proteins. Researchers have developed a huge number of drugs, particularly cancer drugs, that work by essentially throwing a wrench into the mechanics of specific kinases in order to stop cell growth.

Viruses also change the function of cellular machinery – albeit on purpose – but instead of causing cell growth, the machinery is repurposed to produce more viruses. Not surprisingly, viruses take control over many kinases to do this.

It is impossible to actually see which kinases are activated at any time, but since each kinase can attach phosphorylation markers to only a few specific proteins, researchers can look at the phosphorylated proteins to determine what kinases are active at any time.

Some of the more interesting ones include Casein Kinase 2, which is involved in controlling how a cell is shaped. We also identified several kinases that work together in what is called the p38/MAPK signaling pathway. This pathway responds to and controls our body’s inflammation reaction. It is possible these kinases could be involved in the cytokine storm – a dangerous immune system overreaction – that some patients with severe COVID-19 experience.

While identifying the kinases involved in SARS-CoV-2 replication, we were also able to learn a lot about how the virus changes our bodies. For example, CK2 becomes much more active during the course of coronavirus infection and causes the growth of little tubes that extend from the surface of the cell. Under a microscope, it looks as if the cell has a full head of hair. We think SARS-CoV-2 might be using these long cell outgrowths – called filopodia – as viral highways to get new viruses closer to neighboring cells, thereby making infection easier.

There are 87 existing drugs that change the kinase-controlled pathways used by the coronavirus. Most of these drugs are already approved for human use or are currently in clinical trials to treat cancer, and could be quickly repurposed to treat COVID-19 patients.*

Continue reading “Two New Approaches to Treating COVID-19”

Creeping Back

I work at a museum in downtown San Francisco. Which is to say, for the last three+ months I have been working from home at a museum in downtown San Francisco: The American Bookbinders Museum. The hiatus, as horrible as it has been for all the cultural organizations around the country and in SF in particular, has permitted our staff of three (myself, our Executive Director, and the Collection Manager) to do a thing that otherwise would have been accomplished much more slowly and around the edges of all the other things that have to get done daily: we have crafted an audio version of the docent-led/self-guided tour.  Just in time, too. The docent tour is an artifact of pre-Covid life: people crowding around the docent, objects being passed from person to person… your basic contagion nightmare. With an audio tour, visitors can learn about the history and processes of bookbinding via earbuds and their phone, in a low-virus-low-risk way.

So well done us, and the minute the City gives us permission to open, all we have to do is open the doors and we’re ready to go, right?

Actually, no. As the Operations Manager, I handle a weird and diverse range of chores from designing our print materials to ordering toilet paper. So I am in charge of reopening, from the purely practical standpoint. You know what we have to do first?

Flush the pipes. We have several notices from the EPA about what has been happening in our pipes over three months of almost no water being run through them. Short form: still water breeds bacteria. So the first thing I do is open all the taps and flush the toilets repeatedly. Since this is California, where the threat of drought is pretty much a given, this feels distinctly chancy, and yet…

Next: dusting and cleaning in the usual way, and then disinfecting. Which, it appears, I’d been doing wrong all these years. You have to leave your wet disinfectant on the surface you are disinfecting for anywhere from 30 seconds to 10 minutes, depending on the disinfectant (the EPA and the CDC will give you charts of dilution and waiting time, and those bleach wipes that I was using before Covid? They’re great, as long as you use one wipe per about 2 square feet. The minute the wipe no longer feels dripping wet, it’s done, pull another one).

When everything in the museum is clean and disinfected, there will be new signage to put up: the “don’t enter if you’re sick” signs and the “maintain 6 feet of distance” signs, and the “wash your hands, and remember to close the lid on the toilet before you flush” signs. And checklists on display everywhere to show when each area was last cleaned.

In a museum with three employees and a relatively unusual subject matter, this may seem like overkill. Some of it is at least as much for the peace of mind of visitors as for us public-facing employees. But really, the more I learn about Covid and what kind of havoc it can leave in its wake, the more I believe you can’t take shortcuts with this stuff.

If you want me, I’ll be spraying things with a 5% bleach solution.

Sewing as Fast as I Can

When the pandemic hit and the museum I work at was shuttered temporarily, I decided that I would make masks for medical workers and others who need them. Remember back to those long-ago days three months ago (!!) when frontline medical workers couldn’t get PPE for love or money, and were wearing their N95 masks over and over? So I did some research, trying to find out what style and features the local medical folk preferred–and got a lot of conflicting advice. Finally I settled on a pattern that could be made up fairly quickly, with fabric I had on hand, and started sewing.

I should note that the fabric I had on hand was, some of it, interesting. Almost two yards of fabric with 1930s-40s SF pulp magazine covers on it. A yard or so of what looks like a Candyland game board. An abstract star-scape. You ask a science fiction writer to make masks, you are likely to get interesting, if not downright eccentric, material choices. Continue reading “Sewing as Fast as I Can”