Since 2014, Ville Paavilainen’s laboratory at the University of Helsinki has been investigating a molecule, which now shows promise in targeting the new coronavirus.
This work could lead to development of a new drug to help alleviate symptoms and prevent progression of COVID-19, states the researchers.
Paavilainen’s laboratory conducts basic research focused on the protein homeostasis of cells and proteins secreted by cells. “We are investigating a range of small molecules that are disturbing this homeostasis to learn more about cellular processes. To us, they serve as a tool, but the same molecules can also work as precursors for drugs.”
The secretory pathway proteins Paavilainen studies have a key role in many cancer types as well as in diseases where the structural problems found in the proteins produced, known as misfolding, have an effect on disease progression. Among other disorders, misfolding is characteristic of cystic fibrosis.
A protein grappling hook
Coronavirus-related news have frequently mentioned a so-called protein grappling hook, found on the surface of the coronavirus and used by the virus to attach itself to cells in the human respiratory tract. However, attaching and entering are only the first step on the path to success for the virus. Once inside the cell, the pathogen needs to multiply, and most viral proteins needed for replication are produced in a certain organelle of the human cell: the endoplasmic reticulum in the cell membrane. The assistance provided by the protein machinery of the endoplasmic reticulum is vital to the virus.
It is precisely this machinery and the molecules inhibiting its function that Paavilainen’s laboratory has been focusing on.
“Now, all of a sudden, a site of action was identified for this same small molecule in the coronavirus. In other words, we have been tinkering with a potential coronavirus drug precursor in our laboratory for a long time.”
“We have studied a molecule that inhibits influenza and Zika viruses, which is also a promising drug candidate for certain cancer therapies. Now, all of a sudden, a site of action was identified for this same small molecule in the coronavirus. In other words, we have been tinkering with a potential coronavirus drug precursor in our laboratory for a long time,” says Paavilainen.
The work is based on structural biology data continuously produced by Paavilainen’s laboratory in cooperation with its partners. While doing this, they are also looking in more detail into how molecules disruptive to viruses affect the coronavirus.
“We are experimenting in a cell culture model with inhibitors on virus specimens extracted from patients,” says Paavilainen.
The next steps
The next step is animal testing on mice. The goal is to discover a drug that could be used broadly in different stages of treatment.
“As a biochemist, I believe this drug type could be used to treat patients in all disease stages where viral multiplication and the resulting cell destruction aggravate the disease. Based on what I know, this already begins before symptoms start to show and continues almost until recovery,” says Paavilainen.
In the best-case scenario, the drugs would also benefit healthy individuals. “They could be used to inhibit the ability of the virus to infect and replicate among the asymptomatic population.”
A COVID-19 research group
Paavilainen’s workplace is located in a dedicated laboratory on Viikki Campus at the Institute of Biotechnology, part of the University of Helsinki’s Helsinki Institute of Life Science (HiLIFE). In recent weeks, he has also been serving as a member of a COVID-19 research group that was quickly assembled from among the University community.
Knowledge of epidemics and viruses was already available in a number of research groups active in the faculties of the University. Alongside Paavilainen, the extensive group of specialists includes Professor Olli Vapalahti, who specialises in zoonotic diseases; Tarja Sironen, associate professor of emerging infectious diseases; and Professor Mark Daly, a specialist in genetics.
“Had we been forced to begin our work without previously acquired knowledge on other coronaviruses at the beginning of the outbreak, we would be years behind our current situation. You can never know in advance which discovery will turn out to be useful in the end,” says Paavilainen.
Source: Virve Pohjanpalo, The University of Helsinki
Photo: Paavilainen Lab