Tuesday Update for 2021-02-23: Peptides
Herewith three items of pandemic news you may have missed recently: A caution for those scheduling mammograms around the time of vaccination; sterilizing immunity from vaccines; and peptides for prevention and treatment. Plus news briefs and a frippery.
Dr. Anthony Fauci said in a recent interview that the focus of scientific work on Covid-19 will be shifting away from vaccines and toward prevention and treatment by drugs that can directly attack the virus. As if to underscore his point, two research groups have just published work on peptides that can bind to SARS-CoV-2 virus and inactivate it.
- The earlier-stage report comes out of Ohio State University and describes the researchers’ hunt for molecules that could gum up the SARS-CoV-2 spike protein’s binding to ACE2 receptors on a cell. The peptides they settled on work in somewhat the same way as the antibodies with which we may be more familiar. The scientists found their candidate peptides not by looking at structures on the spike, and developing molecules to match their confirmation, but rather by examining the detailed geometry of human ACE2. Their peptides mimic an ACE2 ribbon-like substructure (illustration at upper left) that comes into play early in the virus’s process of binding to and infecting a cell. As the OSU summary linked above describes it, “These peptides effectively trick the virus into ‘shaking hands’ with a replica rather than with the actual protein on a cell’s surface that lets the virus in.”
In their published paper, the researchers describe performing lab experiments with both spike-equipped pseudotyped virus and actual SARS-CoV-2 virus to determine that their peptides prevent the viruses from infecting human cells in a Petri dish. (Working with actual infectious SARS-CoV-2 virus requires a biosafety level 3 lab, of which there are only around 200 in the country, so I can see why the researchers did as much as they could with pseudotyped virus.)
This work is in early stages. The research group summarizes:…our proof-of-principle study that SARS-CoV-2 can be inhibited by small peptides will further allow for the successful development of engineered peptides and peptidomimetic-based compounds for the treatment of Covid-19.
- The work that is farther along is from Columbia and Cornell. These researchers have packaged their [SARSHRC-PEG4]2-chol peptide in a nasal spray, which they call an “HRC lipopeptide fusion inhibitor,” and demonstrated in ferrets that it completely stops the spread of SARS-CoV-2 — a first in any animal model, they claim. (Remember, though, that ferrets are not people.) The peptide is stable at room temperatures. Here is the paper in Science. They do not mention working toward human trials, but I have to believe those are in the works.
Vaccines and sterilizing immunity
We are beginning to get more solid answers to the question posed last time: Can people who have been vaccinated transmit virus? The level of sterilizing immunity reported out of the UK and Israel could quite plausibly get us to herd immunity.
United Kingdom: The SIREN study, for which I posted a pair of preliminary links last Friday, has now published its results (Public Health England summary, full paper), and the results are most encouraging. The Pfizer / BioNTech vaccine provided 70% protection from infection by day 10 after one dose, and 85% after the second dose.
Israel: Less solid, in terms of its publication status, is a study reported using data from Israel, the nation that has vaccinated a higher percentage of its population than any other.
We are cautious of scientific research released as a “preprint” — without benefit of peer review or formal publication — and even more so of work announced via press release. This Israeli report is in a whole other class of don’t-bet-the-farm-on-it. It is reportedly a 22-page paper from researchers at Pfizer and the Israel Ministry of Health, leaked to an Israeli journalist and partially posted, in screen shots, on Twitter.
Technology Review has a summary of what the journalist, Nadav Eyal, reported that the paper says. Based on the experience of hundreds of thousands of vaccinated Israelis, the Pfizer vaccine (a week after a second dose) prevented over 89% of infections, including asymptomatic ones.
An unexpected wrinkle has come up as people get vaccinated in significant numbers. One effect of the mRNA shots can be swelling of the lymph nodes (lymphadenitis) under the arm on the side where the shot went in. This is normal — by one estimate it occurs in about 11% of people following the first shot and 16% after the second. It seems to be more likely with the Moderna vaccine. It indicates that the immune system is working overtime to learn about SARS-CoV-2.
But swollen lymph nodes are also a sign that doctors look for on mammograms as an early indication of breast cancer.
Women who have a mammogram sheduled may want to move it ahead of their first shot, if possible, or delay it until
four months after the second shot. [Note added 2021-02-23: Other sources say 3-6 weeks following the second shot. I was not able to find exact advice on the CDC site.]
The doctor quoted in the Pittsburgh Post Gazette article linked above does not recommend such a delay, especially for women who may have missed an annual mammogram in 2020 due to the pandemic. He suggests letting medical staff know if you are getting vaccinated around the same time. They will still call you if they see swollen lymph nodes, but at least everyone will know that it is not necessarily the cause for alarm that it might be under other circumstances.
- Single shot — Two new studies say that people who have recovered from Covid-19 should get vaccinated, but with only a single shot of Pfizer or Moderna vaccine, which nominally require two shots for full and lasting protection. The reason is that the natural Covid-19 infection acts pretty much like a first shot of vaccine, prompting the immune system to pump out antibodies and to remember the antigens of SARS-CoV-2. A “booster” vaccine shot causes antibody levels so shoot up by as much as a factor of 10.
- Surveillance for variants — Ars Technica has a long-form report on how ill-prepared the US is to keep a close watch for SARS-CoV-2 variants on these shores, and what it will take to build up that capability. Along the way it touches on a report outlining seven American variants that turned up in a search recently (here is a preprint describing this discovery).
- Delaying second AstraZeneca shot can increase efficacy — Researchers looking farther into the (rather messy) data of the AstraZeneca Phase III trials in the UK, Brazil, and South Africa have found that delaying the second shot from 6 to 12 weeks after the first can increase protection by 47%.
- More coopetition — Sanofi, which as we noted is helping Pfizer with vaccine manufacture, has also reached out a hand to Johnson & Johnson for help along the same lines. The company, along with partner GlaxoSmithKline, is also restarting testing on its own vaccine candidate after its earlier setback.
Two fripperies today. The first is for those who, like me, are missing their favorite bar: follow that link to queue up the sounds of people talking, the bartender working, rain on a window, a late-night city street. You can layer more than one at a time.
The second break from Covid-19 seriousness is the chance to see how icebergs float. Visit Iceberger for a canvas on which you can sketch the outline of an imaginary iceberg and watch while it finds its 90-10 equilibrium. This site was produced by an iceberg scientist.
Tuesday Update for 2021-02-23: Peptides — No Comments
HTML tags allowed in your comment: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>