The Wuhan Coronavirus is stealthy, quick to spread, and often deadly. The Chinese government gave the virus a head-start by covering up the infection for seven precious weeks — and missed the opportunity to reduce the spread by 95%. But the rest of the world has a few tricks up its sleeve. It may be time to pull out the big guns and let the mad dogs off their leash.
The Summit, or OLCF-4, supercomputer housed at the Department of Energy’s Oak Ridge National Laboratory (ORNL) in Tennessee was used by ORNL researchers to run thousands of simulations that analyzed which drug compounds might effectively stop SARS-CoV-2 from infecting host cells. It identified 77 small-molecule drug compounds, an achievement ORNL researchers said is a key step toward developing the most effective treatment against this highly-contagious disease.
ORNL researchers have published their findings in the journal ChemRxiv. Summit is currently the fastest supercomputer in the world, and is capable of 200 petaFLOPS. It was developed by IBM for use at ORNL and reduced the time it took to screen for useful drugs from months to just days. __ Intl Bus. Times
We know that several drugs have exhibited preliminary signs of effectiveness against the novel coronavirus 2019, including the anti-malarial drug chloroquine. But none of them are ready for prime time just yet, and even when approved under the new “compassionate guidelines”, they will probably not be magic bullets against the virus. But they are a start, and a few of the treatments will likely be helpful in mitigating the severity of the disease in many cases.
We have already looked at using the convalescent plasma of recovered patients as “blocking antibody therapy,” for cases that are critical, or heading in that direction. And we have looked at new monoclonal antibody therapies.
Wuhan Coronavirus Is Muddying the Waters
Politicians across the US are using the Chinese virus as an excuse to grab more governmental power. But the side effect of all of that is to badly hurt the economy — a cure that can be worse than the disease. Many people are wondering whether it was necessary for the politicians to bring about a recession, when other approaches might have worked better.
Another reason Americans are “sick and tired” of this situation, is that many of them have been sporadically “sick and tired” through the winter, with flu-like symptoms. At the peak of flu season in February, only 30% of those with flu symptoms were testing positive for either Influenza A or Influenza B.
How many of these 70% with flu symptoms who tested negative for influenza A or B, were actually experiencing infection with novel Wuhan Coronavirus? It is possible that Chinese tourists and other travelers from Hubei province have been bringing the virus to North American tourist sites since December, when the virus was spreading rapidly inside that part of China. Perhaps you yourself remember that “cold” or “flu” you experienced a few weeks ago? Perhaps it was really something else.
Don’t Panic, Nuke Something!
Viruses can be stealthy and resourceful in their deadly passage through human populations. But humans have brains. And in the long run, that should make all the difference. And because humans also have strong emotions, they tend to remember when they have come out on the short end of the stick. They want to destroy the offending party.
Choosing the Targets
When going after Wuhan Coronavirus for the kill, we should choose our targets carefully:
- Target: reproduction
When virus’ RNA genome first enters a cell, it interacts with the host’s protein-making machinery, using it to make proteins that can copy RNA molecules.
These RNA-copying proteins, called “polymerases,” make an enticing target for therapies. Because host cells don’t naturally have them, therapies that target these RNA-making proteins should have a lower chance of off-target effects. Block these RNA polymerases, and the virus can no longer reproduce, stopping an infection.
- Target: processing
RNA copying polymerases aren’t the only potential therapeutic targets for a coronavirus. Their RNA polymerases are initially made in forms that aren’t fully functional; instead, they must have small pieces snipped out in order to adopt their mature configuration. Coronavirus RNA therefore encodes two or three proteins that do this cutting. They belong to a class of proteins collectively termed “proteases” for their protein-cutting ability. Proteases typically have a very specific site where the cutting takes place, and any chemicals that can fit into this site might shut the protease down. Not surprisingly, such chemicals are called protease inhibitors.
This approach has been used successfully against other viruses, notably including HIV. Scientists have now found that protease inhibitors targeted to HIV might have activity against coronavirus, despite the fact that these viruses are unrelated.
- Target: packaging
After replication, viral RNA can’t continue an infection until it is packaged up into a mature virus and gets outside of the host cell. This requires special packaging proteins. (In coronavirus, these proteins do double duty by also helping the viral RNA link up with its copying enzymes.) This packaging step would seem to provide a great opportunity for targeted therapy, as disrupting it should limit the amount of functional virus that gets made and exported from any particular cell.
- Target: the viral shell
That leaves the spike protein. Spike is a complicated protein that provides a wealth of targets for potential therapies. As the most prominent feature of the virus’ exterior, spike is the main target of antibodies against the virus produced by the immune system.
- Target: new infections
The final step in the virus’ life cycle is infecting a new cell… This series of events provides potential targets for therapies. One of these targets is the drop in pH. This is the step that’s targeted by chloroquine, the antimalarial drug. Chloroquine can cross membranes and so can enter the sac containing the virus. Once there, it can neutralize the pH.
… The host cell proteases themselves also make a tempting target. A paper we mentioned above identified a protease that appears to be essential for the coronavirus spike protein’s activation. That team showed that an inhibitor of this protease blocked coronavirus infections in cultured cells. The inhibitor has been approved for use in humans by Japan, so this may be another promising avenue for tests. (Racaniello notes that this protease is also used to activate influenza viruses.)
- Target: Beyond the obvious
A recent article in the New York Times described how scientists have identified hundreds of proteins made by host cells that interact with proteins encoded in the coronavirus genome. We don’t know the significance of most of these interactions and whether or not they’re important or coincidental, but any of them could potentially lead to a therapy. That would, however, probably take longer than a targeted therapy, since there are more steps involved in screening for effective drugs than there are in, say, screening a library of known protease inhibitors against the coronavirus’ proteases.
There’s also the potential to intervene at the level of the body’s response to the virus, rather than targeting the virus itself. The more damaging consequences of some infections come from an exaggerated immune response to the virus. Biotech giant Genentech, for example, announced on Thursday that it was starting clinical trials of an immune-dampening treatment on hospitalized coronavirus cases.
If any of the approaches described above—or one we didn’t consider—is even moderately effective, it could radically change our circumstances. It could ensure that far fewer coronavirus cases need hospitalization, and that fewer of those that do require critical care. A country’s healthcare system could then continue functioning in the presence of a higher rate of infection, which in turn could mean that less dramatic social restrictions are required. If carefully managed, this might even allow countries to allow enough infections so that they achieve herd immunity before the availability of a vaccine.
__ Ars Technica
Politicians are throwing the economy under the bus without having had any meaningful public discussions — and without giving the public a choice in its Wuhan viral destiny:
Focus on vulnerable populations
It is people in these vulnerable categories who are most likely to require hospitalization if they contract the virus. Flattening the curve among them would accomplish most of the public health benefits that attempting to flatten the curve among all of us is intended to achieve.
The rest of us could have gone about our quotidian activities. More of us might get sick sooner. But we would get well, and back to work, quickly. There would have been disruptions in workforce availability that businesses would have had to work through and around. But nothing like the current massive shutdowns.
There was never a formal decision to prioritize flattening the curve for everyone over everything else, regardless of the disruption or cost. Nor any formal consideration (and rejection) of the alternative of seeking to flatten the curve and protect just the more vulnerable population. It just sort of happened. __ Was Recession Really Necessary?
Heavy-handed decision making which results in economic distress for large numbers of people, is not a good way to get on the good side of the people you are supposed to be serving.
It seems a fool’s errand to pre-emptively and indefinitely risk everyone’s livelihoods without hard information about what is happening and a risk assessment that includes the serious dangers of killing the U.S. economy, not what computers project will happen with lots of missing, unreliable, and rapidly changing information. __ The Federalist
We have been fed “worst case scenarios” throughout this political hysteria. Perhaps it is time to give the public the full range of projections, and while “protecting the most vulnerable” and making prudent recommendations, we let the rest of the people make their own decisions.
… officials don’t appreciate the financial vulnerability of America’s 30 million small businesses when they are ordering all‐encompassing shutdowns. California has ordered a general economic shutdown except for essential services. Pennsylvania has ordered “all non‐life‐sustaining” businesses in the state to close. All mining, construction, most manufacturing, most retail trade, and many other industries must close based on a government central plan. These sorts of actions are very heavy handed. Governments are offering emergency businesses loans, but that won’t compensate for the massive income loss imposed if this extends for more than a few weeks.
Policymakers face tough decisions in the days ahead, but I fear that they are swinging too far toward virus control at all costs. We should be putting more weight on the economic and health damage that will be risked by extended business shutdowns. __ https://www.cato.org/blog/coronavirus-politicians-vs-economy
Do They Want to Make Beggars of Everyone?
Give a man a free house and he’ll bust out the windows
Put his family on food stamps, now he’s a big spender
No food on the table and the bills ain’t paid
‘Cause he spent it on cigarettes and P.G.A
They’ll turn us all into beggars ’cause they’re easier to please
They’re feeding our people that Government Cheese
__ RainMakers “Government Cheese”
F* that S* ! Let’s just nuke the bastard.