Doctoral student Mohammad Azharuddin and Jorma Hinkula measure the amount of antibodies against the coronavirus. Photo credit Alfred Rombo
“The group of coronaviruses has long been known, but they have been considered to be just rather mild cold viruses. The first SARS virus was an exception. When the new coronavirus appeared, nobody expected that what started as a small epidemic in Asia would suddenly be found in a ski resort in Italy and subsequently spread rapidly all over the world. I knew that influenza viruses can do this, but I could never have imagined that a coronavirus could be so dangerous. It was a shock”, says Jorma Hinkula, professor of molecular virology.Professor Marie Larsson and professor Jorma Hinkula are involved in the research collaboration. Photo credit Magnus Johansson
He and the other virus researchers at the Faculty of Medicine and Health Sciences at the university were nearest neighbours to the hospital. They realised at an early stage that the medical care system needed to know whether a patient in care had been infected with the new SARS-CoV-2 virus or not. Jorma Hinkula’s expertise in developing a diagnostic test to determine whether a patient has developed antibodies against the virus would be useful. But he lacked both money and commercially available reliable reagents.
“I was in despair. I remember meeting a colleague who asked why I was looking so depressed. I said that I couldn’t get hold of the reagents for the antibody tests.”
From patient down to the molecular level
The colleague suggested that he contact researchers in structural biology and protein chemists at the Faculty of Science and Engineering in the university. After that, things happened quickly.
“I was given the names of two researchers, who in turn had many contacts. We met for the first time the very next day.” From a position of having nothing, he was suddenly facing an amazing opportunity.
The goal of the researchers was to develop a rapid diagnostic analysis that could demonstrate whether a patient had formed antibodies that could incapacitate the virus.
“It was marvellous to meet these generous researchers who could come up with the first reagents in just a few days, so that we could start using them. I was deeply moved”, says Jorma Hinkula.Eleonore von Castelmur, expert in structural biology, was one of the researchers in the collaboration, which included also groups led by Maria Sunnerhagen and Daniel Aili at the Department of Physics, Chemistry and Biology, LiU, and researchers at the University of Toronto. Photo credit Anna Nilsen
One of the scientists who got involved in the interdisciplinary collaboration was Eleonore von Castelmur. She studies the structure and function of proteins, and was so fascinated by viruses that she targeted them in her research, to understand them better. Her experience of virus proteins was important to the work.
“We decided to help, so that we could cover the complete pathway here in Linköping, from the patient down to the molecular level. We produced many different variants of the coronavirus spike protein, from small peptide fragments to the complete protein, in our collaboration network”, says Research Fellow Eleonore von Castelmur.The spike protein on the virus surface consists of three identical molecules. One of the molecules is shown in rainbow colours, and the surfaces of the other two in grey. The part that the virus uses to enter a cell and infect it is seen at the top (green). Photo credit Eleonore von Castelmur, based on 6VSB/6LZG(SN1b)
Follow patients for several years
The antibody test developed by the researchers showed that most people who are infected develop a protective immunity, which is a great relief. The researchers could also confirm the new diagnostic test for coronavirus in the medical care system. The collaboration is now continuing together with physicians, and patients who have been infected by Covid-19 will be followed for several years.
“The virus can affect many different organs, and maybe it doesn’t behave the same way in the lung as in the intestine or liver. The particular pattern of symptoms displayed by a patient depends on which tissues the virus has infected. And we also don’t know how long the virus can remain in different tissues”, says Jorma Hinkula.
One important question is whether the researchers can find patterns in the immune response that are related to the prognosis. They also want to identify which parts of the virus protein it is most effective to form protective antibodies against – both after infection and after vaccination.When the coronavirus infects a cell, the receptor-binding domain (grey and purple) on the virus spike protein binds to a receptor (light green) on the cell. Parts of the protein that play important roles are shown in detail. One of the peptides that the researchers synthesised to use in antibody tests is shown in dark purple. Photo credit Eleonore von Castelmur, based on 6VSB/6LZG(SN1b)
They see several benefits with collaboration between patient-centred research and basic research driven by curiosity.
“In this pandemic, it was an enormous advantage that the scientists had studied coronaviruses for many years, even if these viruses were considered to be relatively mild and slightly weird. This allowed the researchers to map important properties of the new coronavirus in record time. We will not know in advance what causes the next pandemic, so it’s extremely important that basic research is properly funded. You never known when knowledge that has been generated from curiosity-driven research will be decisive in being able to react rapidly”, says Eleonore von Castelmur.
