HALOS webinar series - an online forum for industry and academia to discuss and learn about synchrotron and neutron applications in life science and innovation.
- Microscopy at MAX IV - Karina Thånell, MAX IV
- Inside the Coronavirus - Andrea Thorn, Universität Hamburg
- SAXS in the fight against viral pandemics - Isja De Feijter, XENOCS
- Unlocking the secrets of bone by multimodal and multi-length-scale X-ray 3D imaging - Henrik Birkedal, Aarhus University
- Combined spectroscopy and scattering to resolve (bio)molecular processes - Cedric Dicko, Lund University
- Molecular mechanisms underpinning epigenetic regulation by the Human Silencing Hub (HUSH) complex - Christopher Douse, Lund University
- Sample requirements for time-resolved experiments with biomolecules at European XFEL - Robin Schubert, European XFEL
The webinar has two parts; the first part is about the composition of Andrea Thorn's workgroup and the second part is about the group's work on coronavirus structures.
In her introduction, Andrea Thorn explains why the virus is not large enough to be seen with visual light. To visualize the virus you need neutrons, electrons or X-rays, and this is why large facilities are essential in research on the coronavirus.
Some of the most common problems in the group’s work are that they cannot see everything they want in the structures they have solved, or that parts of them are wrong. Another problem is model bias, and another is that the model sometimes does not fit the data, which makes it hard to picture the virus. All of these problems usually result in errors in structures. Being in the midst of a pandemic adds complications to the work. It makes it harder to focus, and you also have less access to experts working from home. On top of this there is high pressure to publish fast since the demand for coronavirus structures is very high, which leads to increased errors in publications and writings. This lead to Andrea Thorn starting the workgroup.
The workgroup model
The workgroup contains 23 people from seven different countries and nine different time zones around the world. They work with evaluating and improving published SARS-CoV and SARS-CoV-2 structures, to make sure that there are as a small number of faulty structures as possible out there. Most of the team members are methods developers in structural biology, which makes them uniquely suited for the task since they are specialists in solving structures. The team members use different programs in their work, amongst them are two programs that the workgroup developed themselves; HARUSPEX and AUSPEX.
Results and impact for the life science sector
Andrea Thorn gives two examples of parts of the virus that are viable drug targets, and those are papain-like protease and RNA polymerase. Once the virus is formed it produces a polypeptide chain of proteins. This polypeptide chain has to be cut into functional NSPs, and this is done with the papain-like protease. RNA polymerase makes more RNA in the host cell and then excretes it so that it can be used in future viruses. If you could stop one of these processes you could stop the replication of the virus.
Thorn's workgroup has also made a lifecycle of the coronavirus, as well as a physical model of the virus.
About the webinar
The coronavirus needs host cells to replicate
The coronavirus spreads by replicating RNA in host cells, which it enters using Spike proteins (S proteins). The host then produces new proteins and virus particles that are expelled and can infect new hosts.
How to combat a virus with the help of SAXS and WAXS
There are two approaches to combat the virus: the development of a vaccine, or the development of treatments. Both of these generally follow the same process that can be explained in five different steps: target identification, lead finding, drug delivery, the formulation stage and the clinical phases. SAXS and WAXS can be of help in all of these steps. Isja De Feijter's group also developed an instrument called the BioXolver to bring SAXS and WAXS to different laboratories.
SAXS and WAXS stand for small and wide-angle X-ray scattering. They shoot X-rays onto a sample and collect the scattering on a 2D detector. A large sample to detector distance gives small angles, and a small distance gives big angles. Hence, SAXS can be used to look at bigger structures, and WAXS can be used to look at smaller structures.
There are many benefits to using SAXS and WAXS, not only do the methods provide a lot of information about samples and particles, for example about size, shape, internal structure and order and orientation of samples, they are also suitable for many different types of samples, and the results are statistically relevant with just one measurement. In addition, usually less sample preparation is required in comparison to other methods. SAXS can also be used as a complementary method when preparing for electron microscopy in e.g. coronavirus research.