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    • How Ebola Aerosolized in Pigs Could Kill Millions
      Up until today I’ve been moderately sanguine about Ebola outside of some poverty struck African countries with compromised health care systems (and places like Greece.)  The main danger is incompetence and austerity, as with the CDC and Texas fumbling their Ebola cases. No more. Ebola is aerosolized in pigs.  This may not seem like a [...]
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Why Ebola spread in Dallas: Americanism

Lorenzetti’s Allegory of Good Government, 1339

We’re number one.  That’s what we always tell each other.

We have the best health care in the world.

Our public safety institutions are number one in the world.

We  are the richest country in the world.

We are supremely over confident.

How many people know that when Dr. Kent Brantley and Nancy Writebol returned from Liberia with ebola that their care was paid for by Samaritan’s Purse?  I’ll bet a lot of us just assumed that the US government picked up the tab for the flight, biocontainment units, ZMapp doses and hospital stays.  Not so.  So, who is paying for the transport and treatment of Nina Pham and Amber Vinson?

Probably a few more of us have questioned whether money was behind the shoddy care that Mr. Duncan got in Texas.  I have.  I’m betting that his lack of insurance and status as a foreign national had a lot to do with why he wasn’t immediately isolated when he first came to the hospital and why he was left in the ER for hours, some nurses say days, before he was transferred to a critical care unit.

As for the best health care in the world, the nurses were very unprepared for ebola.  The biggest chunk of the blame goes to the hospital.  It’s a hospital for the middle class and those who can afford the best health care in the world.  That’s where people go to have their babies and bypass operations.  Maybe they didn’t associate their kind of hospital with an epidemic in a third world country.  Bad things happen to THOSE people over there in Africa.  Not their kind of people in Dallas.  At best, that’s a benign form of American narcissism.  We’re so used to having clean water and streets and good food.  So, why should the hospital get all Girl Scouty and be prepared for a situation that will never happen to it?  Training for such an eventuality takes time from nurses doing their duties and time is money.  It’s the American way.

The CDC seems to have vastly overestimated the outcomes of our educational institutions, especially our K-12 schools, where everyone should have a pretty good understanding as to where Liberia is.  But then again, Liberia was a state created by former American slaves in the 19th century and Texas is a state notorious for trying to rewrite the past when white Americans might have done bad stuff to anyone.  But still, don’t these ER intake people, nurses and doctors watch the news??  At least one nursing supervisor seems to have been on the ball and insisted on moving Mr. Duncan to an isolation unit instead of letting him shed viruses all over the ER but she was shot down by her administration.  Still, you’d think that a hospital so concerned with its reputation and profits would have been more proactive in limiting the damage that his presence was causing.  Not so, apparently.

And what was the hospital thinking when they gave antibiotics to Duncan when they hadn’t bothered to find out whether he  had a bacterial infection that required them?  Does Texas Health Presby Hospital routinely overprescribe antibiotics?  Is this a hospital or a student health center?

What were Republicans and Democrats thinking when they cut the budget for the CDC by 12% and the NIH by 20%?  Friedan said yesterday that $30 million was restored earlier this year in an “anomaly”.  How the hell are you supposed to prepare for emergencies if you never know what your budget is going to be from one year to the next?  We complain about administrators making decisions for our health care instead of physicians but our bigger problem is that we have politicians making decisions for our disease fighting institutions.  Should the CDC and NIH know in advance what diseases are going to become epidemic on some kind of 5 year plan and ask for the right budget money in advance?  Or are their functions compromised by their unreadiness brought on by this reckless political posturing?

And everyone, politicians, journalists and people who should know better, is under some mistaken belief that the private sector is going to step up and perform the tasks in research and disease prevention that the CDC and NIH were created to do.  But they’re too busy trying to reap profits for the shareholders to engage in such money sucking activities like research. Meanwhile, we underfund the NIH and CDC.  Is that so Republicans can point to what a sh*%%y job government does?  Are they paying no attention to how our scientific infrastructure is being dismantled in this country and concentrated on a few narrow therapeutic areas?  They are leaving a gap that no one is able to fill.

This may be the richest country in the world but the riches are hoarded by some pretty selfish individuals and we don’t seem to be able to get our act together to force them to give up their loot for the greater good.

A little ray of hope came through yesterday when I saw that some television content providers are breaking away from the package deals offered by cable companies to allow viewers ala carte channel selection.  That’s great because eventually I will no longer have to subsidize right wing propaganda from Fox News or be forced to pay for Fox to mislead unsuspecting American viewers.  I’m betting that a lot of like minded individuals across the country will drop Fox from their lineup the second they are able to do it.

But the damage may already be done.  The Senate may fall into Republican hands this November and in the next two years, the predators who have been stalking us since FDR got us out of the Great Depression will finally be able to finish us off.   The willfully ignorant elderly and angry white males will finally stick a fork in us, and allow the extremists to carelessly destroy Social Security, roll back women’s rights and plunge us back into recession with unrestrained austerity.  The only thing that will stand between the power extremists and us will be Barack Obama.  That right there is a very depressing scenario.  But maybe he will have the courage to stand aside when we finally pick up our torches and pitchforks.

We have been living a myth of our greatness.  We’ve been in denial about how government works.  We have told ourselves lies about how we can “starve the beast” that once made our country a formidable force of good around the world.

I’m only glad that the ebola crisis here will be under control before the next session of Congress begins and before the gung-ho, American exceptionalists who take over show us just how unexceptional we are to the hunters who prey on the young, old, and weak.

Section from Lorenzetti’s Effects of Bad Government, 1339

 

More speculation and budget numbers at Angry Bear Blog.

Another thing that irks me

Vox has a new post about Frances Collins remark that if the NIH had better funding, we would have an ebola vaccine by now.  Vox says this isn’t true.  I think this was addressed briefly during the hearing.  The NIH went for years looking for a partner for vaccine research in the private sector and couldn’t find one.  Finally, they got GSK and another company interested in development.

Here’s what Vox doesn’t understand about drug discovery research and I have seen this repeated time and time again until it has become ingrained and hard to dislodge:

The NIH is not the only player necessary to take vaccines to market. The agency’s role in pharmaceutical development is usually basic research, giving scientists grants to look at how diseases function and what can stop them.

When it’s time to use that science to build a vaccine, that’s where drug companies typically come in, paying for the trials and manufacturing. We don’t know whether, in a world where the NIH had more funding, a pharmaceutical company would have stepped forward to do this. There’s decent reason to believe there wouldn’t have been; a vaccine to treat Ebola, an infrequent disease that hits low-income areas of the world, is hardly a blockbuster.

This is the conventional wisdom but it is incorrect.  The NIH does provide valuable basic research but the key word here is basic.  It’s not like the NIH develops a vaccine that just needs to be “built” by private industry.  It’s the same thing with drugs for cancer or any other illness.  The NIH provides very basic starting points.  After that, private industry has to pour massive amounts of money into research to fill out the details to get it to the point where it can be built.

What Vox and others do not understand is that private industry research is Real RESEARCH.

Now, if Vox wants the NIH to do the same kind of research that private industry is doing, starting with basic nuggets performed in NIH sponsored labs and publishing work that frequently can not be reproduced in private industry labs (I have been there, Ezra Klein), then it will need a lot more funding.

And this may be necessary anyway because private industry has decided that Real RESEARCH is way too risky and it would prefer not to do it anymore. (Hence the hundreds of thousands of layoffs that we refer to as Pharmageddon)  So, if we want a vaccine for anything, it may eventually have to come from the NIH.  That is what Collins is referring to.  NIH can only go so far without a private partnership.  If the partnership isn’t there and funding is cut, guess  what?  No vaccine.

This has been another episode of a former drug discovery researcher fruitlessly trying to correct the record.

“Travel Ban” is the new Republican “Cut and Run”

Remember the Cut and Run vote?  I do.  If I recall correctly, some Congress people nearly came to blows over it.

But just because Republicans keep saying “Travel Ban” doesn’t mean it makes any damn sense.

So, let me try to explain why the travel ban is counterproductive:

As Friedan and Fauci tried to explain, the West African countries affected have very porous borders.  People can get out of them and into them without much trouble.  If you impose a travel ban, you restrict direct flights to the US.  But the routes out of other African countries are not affected.  Heck, you can cross over into Europe or the Middle East pretty easily from Africa.  So, imposing a travel ban does not restrict people in the hot zone from coming here.  What it does is prevent those who would otherwise take the quickest and most direct route from being monitored.

Therefore, a travel ban could actually backfire and allow the entry of unmonitored hot zone travelers.  That is not to say that quarantine is out of the question.  It’s perfectly reasonable.  But try to explain all of that to someone scared senseless by E-B-O-L-A!!!

But the biggest problem with the travel ban argument is that it is so successful at portraying Democrats as being lax, unconcerned and callous.  Congratulations, Republicans.  You have once again pummeled an unarmed opponent silly because, to this date, I have yet to see Democrats come up with two or three word phrases that cut to the amygdala as effectively as the Republicans do.

I can repeat over and over that friends don’t let friends vote Republican but I am having a hard time endorsing the student body presidents on the other side.  They are becoming more and more feckless and can barely defend themselves.

{{exasperated sigh}}

Live Blogging the Congressional Hearings on US Ebola Response

Disclaimer: This is not a panic/hysteria site.  We’re interested in learning all we can about the US response to the disease and whether our governmental institutions are funded adequately to respond optimally.

With that in mind, you can watch the hearings online at PBS.org.  So far, we have had opening statements from the CDC (Friedan), NIH (Fauci), BARDA (Robinson), FDA (Borio) and a representative from Texas Health Presbyterian Hospital.

The most notable announcement so far was from Anthony Fauci from the NIH.  He says that Nina Pham will be transferred to the NIH this evening for further treatment.

Also note that there will be a lot of Republicans and Democrats on this committee who voted to cut the budgets of these institutions when they approved the sequester.  So, keep that in mind when you listen to these bloviators.

And, now, on with the live blog.  Geeks are encouraged to comment because I’m pretty sure there is going to be technical information presented, especially wrt to drug discovery efforts.

 

Clueless scientist asks a very dangerous question

How the world sees scientists. Thank you, Underdog.

Note: Congressional hearings on the US Ebola efforts are going on right now with representatives from CDC, NIH, BARDA, FDA and others.  You can watch it here.  If anyone wants a live blog, let me know.  I invite other geeky types to watch and summarize, especially those of us with knowledge of the drug discovery/biotech area.

********************************************************

No, it’s not me.  I admit to being clueless sometimes but not when it comes to the distribution of information.

I’m talking about Leonard Adleman who wrote an Op/Ed in the NYTimes about how easy it would be to revive smallpox.  The reason it would be theoretically easy is because the sequence for the smallpox virus is available online.  So, some really clever evil genius with a garage lab could potentially order up a copy of the gene from one of the synthetic gene specialists in South San Francisco and piece the sucker together using, oh, I don’t know, a variola, vaccinia or orthopox virus just hanging around.  It sounds complicated and might take some time, and if the independent researcher was born in the 80’s, there’s a good chance he’ll die of the disease if he’s not careful.  But it is possible.

Personally, I’m more concerned about reviving the 1918 influenza strain and getting it to go airborne, which, if I recall correctly, was successfully done a few years ago in Europe.  From what I remember, the researchers on that team suppressed the sequence.  Funny, I can’t seem to google that info.  Hmmm…

But getting back to Adleman, he’s not so keen on us just publishing the sequences on public databases.  Maybe it would be better if we just restricted access and only let the professionals see them.  That’s just nuts for a couple of reasons.  The first is that through the years, I have noticed that the sciences are full of people with psychopathic tendencies.  Fortunately, most of them get promoted out of the lab into management.  But just because they might be working at a prestigious lab with unrestricted access to information doesn’t mean they’re not out to get us.  After all, we still don’t know who did the anthrax attacks and I’m pretty sure it wasn’t a garage biologist.

The second reason is, referring to smallpox especially, we have a vaccine for that.  Oh sure, there will be plenty of thirty year olds who may be at risk but an outbreak would be limited.

And for the people who have extraordinary skill in making lethal viruses, I have a perfect solution: HIRE THEM!  Jeez, why in god’s name would you lay off hundreds of thousands of talented people and have them stew over the MBAs and shareholders who wrecked their careers??  Especially when there are auction sites where they can buy discounted equipment from mothballed labs?

I can’t see a teenager doing this, although we do have a lot of malicious computer viruses so who knows.  But they would have to be trained.  Just getting the sequence is not enough.  It’s not like writing code and you can’t get all your information from a book.  Maybe grad students would be capable if they’re motivated, so you tyrannical PIs out there should be on your guard.  But cooking up stuff in a lab takes practice and some good mentors to teach you how to do it.

In other words, it is possible that some well funded hostile country could fund this kind of work by sending some grad students to study in Dr. Adleman’s lab, for example.  He and his students would always have access to sequence data. But smallpox is not a threat and the other diseases are not so easily made.

But the best reason for not restricting access is that it once again takes out of the public domain millions of sequences for genes and proteins that the independent benevolent researcher has access to.  I think it’s great that the US publishes to the NIH PubMed and the European Mol Bio Organization provides this information for free to anyone who wants it.  Without sequence information, and the tools to process it, small, entrepreneurial companies would not have access to it without paying a fee.  That fee, like the high costs of accessing journal articles, could be a substantial barrier to admission to new businesses and new cures for diseases.

Think of it this way, without the information from sequence databases, Mapp Biopharmaceuticals, the company that discovered ZMapp, might never have gotten off the ground.

It’s unlikely that I’m going to produce an ebola protein in the lab but I’m glad that someone published the sequence data so that another lab could make them, crystallize them and publish 47 different protein crystal structures to the web for anyone to access, including a former drug designer in Pittsburgh.  That means a lot to me.  And maybe some crazy kid out there who likes looking at these things and enjoys protein folds and modeling as much as I do will be inspired to find a cure for ebola and other diseases.

What worries me is that the fear that Adleman is producing will lead to those sequences being locked away forever so that only the rich and well connected have access to them.  It would be the equivalent of the Patriot Act.  We wouldn’t know what we had lost until the new Dark Ages descended on science.  Do we really want to leave this information in the hands of only those who can afford to access it?

 

 

Observing Ebola and some thoughts (not fears)

Note: I am not personally afraid of Ebola. I don’t think even this outbreak will reach the level of pandemic. I worry about the people in the west African nations  who ARE personally affected. I admire the people who have gone there to fight for them.  But, I have to admit to being fascinated by the spread of this disease, the details surrounding it and the affect two cases of Ebola have had on our hospitals and health care system. Also, I think it’s fascinating. I do.

So, what do we know?

UPDATE: Here is the full statement from National Nurses United:

 Statement by RN’s at Texas Health Presbyterian Hospital as provided to National Nurses United

Nurses had to interact with Mr. Duncan with whatever protective equipment was available, at a time when he had copious amounts of diarrhea and vomiting which produces a lot of contagious fluids.

Hospital officials allowed nurses who had interacted with Mr. Duncan to then continue normal patient care duties, taking care of other patients, even though they had not had the proper personal protective equipment while caring for Mr. Duncan.

Patients who may have been exposed were one day kept in strict isolation units. On the next day were ordered to be transferred out of strict isolation into areas where there were other patients, even those with low-grade fevers who could potentially be contagious.

Were protocols breached? The nurses say there were no protocols.

 Apparently the nurses who treated Thomas Duncan didn’t where those “Moonsuits” while exposed to him. Monday evening I saw this video of Gupta suits up in Ebola protective gear according to the CDC protocols.  As you will see it’s lucky he was covered in chocolate sauce and not Ebola vomit: http://www.cnn.com/video/data/2.0/video/health/2014/10/14/sgmd-gupta-ebola-suit-demo.cnn.html.I’m glad I saw this before I heard the statement from National Nurses United (discussed below) — it made it MUCH easier to follow the details:

Nurses’ union slams Texas hospital for lack of Ebola protocol, by Catherine E. Shoichet, CNN

Here’s a look at some of the allegations the nurses made, according to the union:

Claim: Duncan wasn’t immediately isolated

On the day that Duncan was admitted to the hospital with possible Ebola symptoms, he was “left for several hours, not in isolation, in an area where other patients were present,” union co-president Deborah Burger said.

Up to seven other patients were present in that area, the nurses said, according to the union.

A nursing supervisor faced resistance from hospital authorities when the supervisor demanded that Duncan be moved to an isolation unit, the nurses said, according to the union.

Claim: The nurses’ protective gear left their necks exposed

After expressing concerns that their necks were exposed even as they wore protective gear, the nurses were told to wrap their necks with medical tape, the union says.

“They were told to use medical tape and had to use four to five pieces of medical tape wound around their neck. The nurses have expressed a lot of concern about how difficult it is to remove the tape from their neck,” Burger said.

Claim: At one point, hazardous waste piled up

“There was no one to pick up hazardous waste as it piled to the ceiling,” Burger said. “They did not have access to proper supplies.”

Claim: Nurses got no “hands-on” training

“There was no mandate for nurses to attend training,” Burger said, though they did receive an e-mail about a hospital seminar on Ebola.

“This was treated like hundreds of other seminars that were routinely offered to staff,” she said.

Another post covering this topic, No hospital ‘protocols’ for Ebola treatment: US nurses’ group by MICHAEL LANGAN (AFP) has a little more information:

Deborah Burger, the NNU’s co-president, said Duncan’s lab samples were sent in the hospital tube system “without being specifically sealed and hand delivered,” Burger added.

“The entire tube system was potentially contaminated,” she said.

“There was a lot of confusion about (gear) protocol, and frequent changing of instructions.”

The nursing staff said that they were directed to wear standard or generic hospital gowns that are flimsy and could be permeated or ripped.

They also complained that they were advised to use surgical masks, not the plastic welder-type shield mask considered a best option.

And while they wore protective gloves, parts of their heads and necks remaine exposed, she explained

DeMoro pointed the finger not just to the Texas hospital where Pham worked, but at the US health care overall.

It “is a chaotic system,” she said.

If I can find the complete transcript, I’ll add it here because it was an extensive and damning list.

It makes complete sense to me that a hospital, any hospital, wouldn’t be prepared for an actual Ebola patient. The chances have been pretty good for several months that some hospital would get an Ebola patient but predicting which one would have been impossible in advance. However, I am pretty shocked to learn that there’s no “infectious disease kit” that could be sent to a hospital faced with an outbreak something like Ebola. How hard would it be for the Centers for Disease Control (CDC) to stock sufficient emergency supplies that could be sent overnight to any hospital — including a couple of experts.

The nurses statement says that Duncan was left in an area with several other patients for hours before he was isolated. That was bad enough but, things went downhill from there. Couldn’t the Centers for Disease Control (CDC) send an expert to Dallas during those hours? I’m not a medical person but, it seems like the CDC should have a contact list of people – maybe from the US hospitals that have already treated Ebola patients who could help local hospitals control outbreaks of diseases.

So what else do we know?

Nurses wrapped tape around their necks to protect them. (I can’t even control tape on a Christmas present! What would I do if I had to work with Ebola drenched tape after a shift in Duncan’s room?)

Duncan’s lab samples were sent through the tube system without being protected! (I didn’t even know they sent lab samples through tubes, much less Ebola samples!! That’s just gross)

These are some thoughts from a non-medical reader. Again, I’m not afraid. And I don’t think the above issues mean we’ll get an epidemic here.

Ebola Updates: Still no reason to panic

Another big headline at the NYTimes: A Second Healthcare worker in Dallas has tested positive for ebola.

Is anyone shocked?  Please raise your hand where I can see you.

Didn’t think so.

Update: So, now we find that the second nurse who was infected was on a plane from Cleveland to Dallas the day before she reported symptoms.  Ahhh, now here is where Americans should start to get concerned.  Americans get around.  That is, it’s  relatively easy to jump on a plane for a weekend getaway, though why anyone would want to go to Cleveland is beyond me.  Sorry about that, Cleveland.  And Pittsburgh is only a few hours from Cleveland by car.  Nevertheless, there is still no reason to panic, though the CDC seems to think the passengers on that flight need to be tracked down. The nurse landed in Dallas-Ft. Worth on Monday night at 8:16pm and reported symptoms on Tuesday. That is a very tight timeframe so passengers probably have more of a reason to be concerned but not panicked. But the bigger problem is that it will be harder to keep ebola in Texas if infection rates blossom.

Reminder: Back in May, I went to a user group meeting in Cambridge, MA where I met several researchers who had just come back from a visit to the CDC.  They reported that the budget cuts had demoralized the CDC and researchers there sometimes didn’t know who they reported to or who was in their group.  That’s not a slight on the CDC.  It has been a world renowned institution but if you starve it for funds, it is going to have problems.  If you do it over a period of 14 years, it’s going to have BIG problems.

I’m copying a few comments I made in a previous thread on the latest ebola news.

On the CNN report about the Nurses Union that is speaking out for the Dallas health care workers, Katiebird may be posting on this later once she has tracked down some information.  These are just my uninformed, idle speculations to the news that Texas Health Presby Hospital may have put its employees and others at risk:

I read that CNN article late last night and I was shocked but not surprised, if that makes any sense. Shocked because the hospital was caught so unprepared and was really botching it. But unsurprised because it made a lot of sense in how the infection was spread to this nurse. No health care worker in their right mind wouldn’t take the utmost precautions given the media frenzy over ebola.

I could only conclude that the hospital itself was at fault for being caught off guard and, probably, considering cost over treatment protocol. After all, who was going to pay to isolate Thomas Duncan? Rick Perry turned down medicaid expansion and the Texas legislature has severely cut back on state board of health offices. Laissez faire apparently means anything goes when it comes to profiting off of health care and Duncan was a money sink.

The 90 minutes gap where Duncan was with other patients before he was isolated may have referred to the emergency room. Here’s my best guess: The ambulance dumps Duncan off at the ER with a barf bag. He has to sit there with other sick patients while calls are being made to the hospital administrative staff to decide how to admit him. He’s a foreign visitor, not even an immigrant, with no health insurance, dumped on Texas Health Presby Hospital. He doesn’t qualify for Obamacare, there’s no medicaid for him either because, hellloooo, Americans, especially those living in the south, don’t want to pay for the health care needs of foreigners. Are there funds set aside in Texas to manage a highly infectious disease like ebola? Are you kidding?? Decisions, decisions. The hospital might have thought of transferring him elsewhere but I’m betting the other facilities said they were no better able to care for him. It’s your problem.
Damn, Duncan could wipe out the profit for the entire year, what with the isolation and ruining ventilation and dialysis equipment, not to mention how to get rid of hazardous waste.

So, he sat in the ER for 90 minutes, vomiting and sweating all over the chairs and gurneys, before the hospital decides it doesn’t have a choice anymore and has to take him. Who knew how many people came in contact with him while he was shedding billions of viruses? Poor Nina Pham probably did what she was instructed to do with very little CDC oversight.

On the ebola forum symposium held yesterday at the Johns Hopkins School of Public Health that was held yesterday:

Peter Jahrling showed all of the possible drug treatments in the pipeline. It’s a joke. No, seriously. ZMapp looks like the best bet but the company can only make about 20 doses in its next batch. It’s not their fault. They’re just overwhelmed by the scale and logistics.

A couple of vaccines are being tested in the field. And they have to have a control group so 1/3 of the participants are getting Hepititis C vaccine. It can’t be helped but the participants must know that some of these people are going to die. There’s no way around it. That’s the way science is done. And these vaccines are not in anyway ready for FDA approval.

Other treatments are even less ready. Interferon actually makes the infection worse. There’s an interesting research topic. What is it about the cell signaling that makes interferon treatment worse? Then there are a couple of “drugs”. Honestly, I think biologists are analyzing the high throughput data. They think any hit is a drug. The compounds presented may have some efficacy (probably in the millimolar range from the looks of them) but they’re not very bioavailable and the toxicity could be a major problem.
So, in short, we’re pretty much screwed if we can’t get West Africa back under control and the infection spreads.

Not that we have much to worry about here in the US. We don’t. But it’s not very reassuring to me that we are sooooo far behind in the drug discovery area on infectious diseases. Again, shocked but not surprised.

The symposium can be found here. Most of it is School of Public Health academics trying to one up each other on modeling the progress of the disease. It got to be too insidery and less informative after awhile. Jahrling’s presentation was more straightforward, to the point and alarming. If the general public truly understood what Jahrling’s presentation was saying, they’d never vote for another budget slashing Republican. Ebola is only one of a number of devastating infectious diseases that we are not prepared to deal with because we cut funding, blocked nominations, and let private industry, dominated by shareholders and billionaires, dictate the research and manage the pipeline portfolios. It’s baaaaad.

About quick and dirty drug design using publicly available ebola virus crystal structures and the funky vocabulary that goes with it, this is a little primer on what I was initially thinking and about some of the obstacles:

FASTA is a format for amino acid sequences. Every protein has a sequence of amino acids and they are all unique. Families of proteins are related to one another. You can perform an evolutionary trace on a single protein if the sequence of that protein over time has been determined. The FASTA sequence is stored in publicly available databases. The NIH allows access to these sequences for researchers and provides tools to search them. One of these search tools is called BLAST. It can do sequence alignments. So, if you have a fragment of a sequence or a new sequence, you can search the database to find the entire sequence or similar sequences. I used to use a related tool called BLASTp. That allows the user to find protein sequences that have been crystallized and are stored at the RCSB.

So, let’s say you have a protein that you know has mutated away from its original source. In this case, we are talking about the ebola viral proteins. The crystal protein I referred to last night was from a strain found in Zaire, in a place called named after a nurse called Mayinga. But the newest outbreak of ebola is located in West Africa and it is a different strain, therefore, different mutations in the amino acid sequence.

If you designed a drug based on the Zaire Mayinga strain, it may not be effective against the West Africa strain because the amino acid sequences may be different. But we can make a homology model of the new viral protein structure if we know where the new mutations are. It’s the next best thing to a experimentally determined crystal structure.

The questions to ask are: do all of the viral proteins mutate at the same rate? We would know by looking at the latest FASTA sequences and mapping them onto the structure. Can we identify a binding site? The protein I looked at yesterday processed RNA. I can make an educated guess as to where this occurs. But when it oligomerizes, that is, forms a new structure by self assembly, it has a couple of different binding sites. That is, the binding sites of each subunit to the subunits adjacent to it can also be targeted for drug design. I worked briefly on a different oligomer previously and it was possible to create a drug like entity called a paptamer by extracting a chunk of the secondary structure of the subunit and modifying it very slightly. This prevented the subunits from self assembly, or so the theory goes.

But in the ebola protein I looked at yesterday, the protein-protein interactions between subunits appeared to be dominated by beta sheets, which relate to one another along parallel and antiparallel strands. So, extracting a piece of this binding surface would be difficult if not impossible. Another, more complex and time consuming drug design process would need to be done. If it were just a matter of a helix, it might have been a different story. So, this viral protein target might not be amenable to quick and dirty drug design work and it might have to be abandoned for another ebola protein.

In any case, the FASTA sequence is very informative. It has likely been deposited at the NIH. They usually do that for Flu viruses and you can track mutations as they zip around the world. But I’m not sure we have the very latest info for ebola.

Ok, that was long.  I’m going to eat lunch.

 

 

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