Well here we are again holed up in our burrow, with only a few trips out to pick up food or occasionally just to look at the sky and see if the clouds have gone away. It is hard to concentrate on much anything else but learning to adapt to the virus. So, this post will cover some interesting aspects of viruses, picked up during my homework reading in virology, and how they rely on physics principles of symmetry, free energy and stability.
First up, though we should mention an interesting article forwarded to the OCA mail server, in which the author lays out a whole bunch of epidemiological models covering different mitigation strategies for dealing with the virus. I can't say anything about the validity of the author's claims, but you can see right away how complicated the issues are with figuring out what drives the decisions to set policies for public policy. The "hammer" in the title refers to strict isolation measures to block the transmission of the virus quickly, so that we can get back to making a living, and the "dance" refers to the ongoing monitoring and control as needed to bring the hammer back as needed. The paper has main charts and graphs based on epidemiological modeling and seems to be very detailed. I hope some kind of strategy like that might get us out of this situation until a vaccine is available. Anyway, if you follow this type of stuff, check it out at:
In the previous blog post, I mentioned a book on the "Molecular and Cellular Biology of Viruses." It is a good reference book for interested reader, but if you like to listen to lectures, rather than reading a textbook, there is a series of free YouTube lectures titled " Virology" with Professor Vincent Racaniello, Columbia U.
I am finding this series of lectures very interesting. You should have had at least some introduction to molecular biology but the professor does a good job of introducing each topic. This is a convenient way to keep busy and learn something about the virus, which we now shelter in place to keep away from. You can check out the lectures at:
|Screenshot of Virology Lectures 2020 on YouTube (Source: Vincent Racaniello, Columbia, U.)|
In order to talk about symmetry and viruses we must first remember some of the basic biology of virus, which is in this lectures series, and I will review briefly. My review is that of a student, so keep that in mind as you read this summary.
Now that the complete human genome has been sequenced we find a mystery in that only about 1.5% of the genome is associated with making the proteins from which are made. What are all of the other base pairs doing? Some of them are leftover additions made by viruses. The same is found when other organism's genome is sequenced. We see that all of life is based on the same general base pair basis and that every animal, plant, bacteria and virus are all interrelated and we share a common history.
|A big part of the human genome comes from viruses (Source: Vincent Racaniello, Columbia, U.)|
This genome sequencing also applies to viruses and phylogenetic trees can be prepared for viruses too. This way the slight genetic differences between viruses, caused by mutations, allows one to track the history of viruses and find their closest relative. Professor Racaniello told how the current version of the coronavirus now circulating around the world has a closest relative in a virus common to bats.
We need some more biological background before we can talk about the symmetry principles found in viruses. As astronomers we naturally think in terms of distance in light years or megaparsecs and wavelengths of light measured in nanometers (nm). Viruses are in the 20-1000 nm range.
|The tools of viral structural biology (Source: Vincent Racaniello, Columbia, U.)|
Compare these two images of a poliovirus. The one on the left was done with x-rays and the image on the right was done with CryoEM. Now, the resolution of CryoEM approaches the same 3 nm range.
|Different images of Poliovirus for different instrumental resolution (Source: Vincent Racaniello, Columbia, U.)|
The principles of CryoEM start with an electron microscope but instead of staining the samples, the samples are fast frozen instead. The frozen samples have enough contrast that the structure can be seen without staining. The techniques was recognized with the Nobel Prize in Chemistry in 2017.
|All cells have embedded proteins to facilitate transport across the membrane (Source: Vincent Racaniello, Columbia, U.)|
The ACE2 receptor is located in the cell membrane and regulates the amount of ACE (never mind what this stands for now). For anyone on high blood pressure medication you know that removal of high levels of ACE from the blood is a key therapy. But the use of these medications apparently works by increasing the number of ACE2 receptors in the cells in the lungs and blood vessels and might be be reason why more elderly patients are more susceptible to the coronavirus. Again, this is my student view and interpretation of the situation and might not be valid.
Just in case you are curious about what the ACE2 looks like, check out the ribbon diagram for ACE2 as shown in Wikipedia. Each ribbon section corresponds to the long chain of amino acids that make up the protein or enzyme. The ACE2 receptor weighs in at somewhere around 90k Daltons, which o my student approximations represents about 800 amino acids. Without going into an biochemical detail, the ribbon diagram shows the 3-dimensional structure and location of the proteins that make up the protein.
|ACE2 receptor ribbon diagram (Source: Wikipedia)|
Viruses also carry signaling molecules that poke outside their capsid structures. These spikes and knobs, and the corona like spikes on the coronavirus, also interact with the cell and are able to be brought into the cell. The cellular chemistry is such that if an outside molecule has the right signaling molecule as part of its structure, is brought into the cell. Again we see that viruses incorporate and use the same signaling molecules that are necessary for each cell that is required to carry out its metabolic processes.
|Viruses have surface mounted proteins to unlock membrane receptors (Source: Vincent Racaniello, Columbia, U.)|
The next slide summarizes the overall process. The graphic shows the virus particle entering the cell at which time it sheds its protective capsid coating and then the internal cellular machinery transports the DNA to the cell's nucleus, where the normal cellular machinery dutifully turns out the components needed to make more virus particles. Once the virus DNA and capsid coat are complete, normal cellular machinery transports the particle to the cell wall and it is released to carry on its infection outside the cell.
In this next screenshot, which uses the ribbon notation you can see that the structure of of a typical subunit, which represents a 3-dimensional model of the actual protein. The ribbon notation (here where each color, red, blue, brown, and yellow, represents and actually captures the 3-dimensional structure of the protein being modeled.
|Viruses have highly symmetric structures to protect its DNA (Source: Vincent Racaniello, Columbia, U.)|
|The capsid is icosahedron of 20 sides, each made from 3 identical components (Source: Vincent Racaniello, Columbia, U.)|
We are now at a point to recognize why this capsid structure is so important. First of all it protects the viral DNA when the virus particle leaves the cell. Secondly, the capsid structure is easily assembled inside the infected cell, because the structure self-assembles from subunits manufactured in the cell, and with the viral DNA inside, the virus particle can then exit the cell and begin anew the infection process.
The virus particles are said to be metastable. They are just stable enough so that they can survive transport outside of the cell and yet when they get inside the cell they can transition to a lower energy state by ejecting their capsid protective coat. The graphic below shows how this energy transition is much like a load spring in that no outside energy is needed as long as the virus can surmount the energy barrier at which time it is all downhill then in terms of energy. It is interesting to note that these chemical reactions use ionic bonding, rather than the more energy intensive covalent bonding which typically requires energy carriers like ATP to complete the process. So, in one sense, the virus is able to complete its journey without relying on any additional energy from the cell, once that is all of the viral components have been manufactured by the cell and its energy sources.
Viruses are able to achieve this metastability and low energy requirements by using symmetrical arrangement of components.
Viruses are not constrained to have capsids made out of just 60 identical proteins. In order to contain larger and more complex types of DNA, the capsid coat and box must be made larger. The symmetry of larger viruses is based on the same symmetry of the icosahedrel structure but more subunits are combined. So instead of 60 identical subunits, the example virus shown below uses 720 copies of the subunit.
|Magnetic marbles show closed structures made from groups of 5 or of 6 (Source: Vincent Racaniello, Columbia, U.)|
Ok, so that is enough viral homework for this time. The lecture series is much more informative and thorough than I have been in this short summary, so check out the actual lectures if you are inclined. I hope you do see though the connection to symmetry and low energy requirements.
Now, I have to transition to being one of the many judges for the OC Science Fair, which this year has been forced to be conducted over the internet. It won't be the same atmosphere like in previous years where you have hundreds of students and their projects all collocated at the fair grounds. I'm not sure how it will all work out, but at least the students won't have the whole event cancelled or postponed.
Until next time, here from our burrow, stay sane, stay safe,