Emergence of a Deadly Coronavirus

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You too!

I think Israel will come out better than New York. At least I hope so.

I came across this article in the morning:

As the horror known as the coronavirus tightens its grip on the world, and a vaccine is years away, our best hope is an antiviral drug that minimizes the damage caused by coronavirus replication. New data on favipiravir, a repurposed drug originally discovered in Japan, looks promising in trials in China. But nothing is ever straightforward in drug discovery -- and that is no different here. Here's a summary of the new findings.

There is now a potentially important change in the pharmaceutical landscape of anti-coronavirus drugs. Favipiravir, a little-used six-year-old drug from Japan probably isn't a game-changer, at least not yet, but given the urgency of having a drug that can at least control coronavirus infection, favipiravir joins Gilead's remdesivir in the spotlight.

Dose-response curves of favipiravir and remdesivir. The red hatch lines indicate the concentration of the drug required to inhibit 50% of viral growth (this is called an EC50). The lower the EC50 the more potent the drug. Favipiravir is a weak inhibitor of coronavirus replication (62 micromolar - a very high number for a drug). Remdesivir is 80-times more potent (EC50 = 0.77 micromolar), putting it in the same range of other antiviral drugs.

All things equal, remdesivir should be a better drug than favipiravir, since it is 80-times more potent, but in drug discovery, all things are never equal. Potency is only one of the dozens of parameters that determine whether a drug will be successful or not.

Favipiravir (brand name Avigan) is an existing drug that was developed by Fujifilm Toyama Chemical and approved in Japan in 2014 for the treatment of influenza. It has been undergoing clinical trials in China and been used therapeutically in people who are infected in Japan. The drug is not approved in the US; it doesn't work very well for flu, but in 2014 when Fujifilm announced the approval of the drug there was one very important paragraph:

AVIGAN is a viral RNA polymerase inhibitor with a new mechanism of action, inhibiting viral gene replication within infected cells to prevent the propagation. Due to this characteristic, the drug is expected to have an antiviral effect on Avian Influenza A (H5N1 and H7N9) and other viruses, with efficacy already confirmed in animal studies.
The key is "other viruses." Avigan has been used with limited success against other RNA viruses, such as Ebola, West Nile, and Zika.

How well does Avigan work against coronavirus? The results are mixed:
* In one clinical trial of 200 patients in China, people who received the drug cleared the virus (negative test) in four days vs. 11 days for those did not.
* In another trial, patients treated with favipiravir recovered from fever in 2.5 days vs. 4.2 days and also stopped coughing within 4.6 days vs. patients who did not take the drug.
* (This one is big) Patients who took the drug needed to be put on a ventilator half as often as those who didn't.

Perhaps the most intriguing aspect of this story is that very different information is coming from the two countries.

"The drug is very safe and clearly effective...there were no clear side effects."
Zhang Xinmin, director of the Chinese government’s National Center for Biotechnology Development.

The story in Japan is quite different. Favipiravir, like all drugs, comes with its own set of baggage. One of the conditions of approval in Japan was that it would only be allowed to treat serious infectious diseases like avian flu or Ebola for which there were no viable options. This is because the drug is known to cause birth defects and fetal death.

And Japanese health officials reached a decidedly different conclusion about the efficacy of the drug.

"We’ve given Avigan to 70 to 80 people, but it doesn’t seem to work that well when the virus has already multiplied."
Unnamed source from the Japanese Health Ministry, reported in Mainichi Shimbun (one of the major newspapers in Japan.

Some of the data from trials in China seem quite impressive, but the opinions of Japanese scientists are significantly different. On balance, I would say the news is positive, maybe even very positive, especially if the efficacy data holds up in further trials. But be prepared for surprises. The only thing that is clear here is nothing.

Source with the graphics and references: Favipiravir: Another Player In The Coronavirus Drug Sweepstakes

Thanks, Jimmy.

Thanks, Jimmy.

I hope I’m allowed to get tested soon.

Turns out I’ll have to jump through hoops to get tested.

Latest data on emergency department admissions for adults for flu-like illnesses in New York City:



See that massive spike at the start of this month? That spike is much higher than the peak of flu season last year and the year before, and is occurring later in the year.

Day FOUR of the coronavirus lockdown for us older folks. Plenty of things to keep me busy with today.

Last night when my mind became uncluttered and I raced around the track at light speed, I came across another shiny object. I reached out and grabbed it. It turns out it was a box, a game box. So I looked at it. The box read "Grand Theft Auto: The Coronavirus Edition" or abbreviated GTA7.

In this version, it was not about stealing cars, it was all about toilet paper. There was a host of different characters: Preppers, Hoarders, a little old granny pushing a shopping cart full of toilet paper. There were super spreaders who were infected and knew they were infected but wanted to spread it and enhance casualty count. There were spring breakers oblivious to the world around them. There were people wearing N95 face mask, N100 face mask and beyond. People with the full array of home made PPE (Personal Protective Equipment).

Then I thought San Francisco is in lockdown. Many of the game developers are locked away at home. They are afraid and their focus is the coronavirus. So their minds are spinning like a fidget spinner, so it is quite natural for the next round of video games to focus on this crisis with a bit of humor added.

I remembered a movie. It was called "Children of Men". I watched it a few years ago and I liked it. So if you are sitting around at home in lockdown, this might be one of the movies to watch. It was a British movie. In the present pandemic, the elderly are the individuals that are facing death, they are on the front lines. But this movie flipped the threat to the other side. What would happen if a virus just prevented individuals from making children. Slowly the world would become childless. The human race would die away in slow motion and become extinct. And in a way this is what the movie is about. Probably a very depressing movie under the present circumstances. But there is always a ray of hope and this is really the heart of the movie.

Baby born in toilet paper isle.
https://www.ky3.com/content/news/Woman- ... 47811.html

Dr. Fauci is misrepresenting the facts to make it look like the US stopped flights to/from China before Italy did. But the reverse is actually true: It was Italy that did it first on January 31.