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Research on coronaviruses and their enzymes informs responses to the pandemic. (Shutterstock)

Funding basic science research is crucial to our coronavirus pandemic responses

The COVID-19 pandemic has shown the virus to be pervasive and deadly to our most vulnerable. This pandemic is a wake-up call to all the countries that ignored the researchers who warned about the inevitability of worldwide viral infections. No country heeded such warnings.

Read more: The taming of polio and the challenge of the flu

It is the basic science researchers that solve molecular mechanisms for discovery. It is they who raced to identify the new coronavirus, determined how to detect it and how to assess its susceptibility in humans. These foundational studies, summarized here, attest to a community without national boundaries and united to overcome the pandemic.

Several publications in the most prestigious and rigorous of scientific journals reveal results that indicate the means and directions to be taken in the short term, as well as the strategy to mount effective treatment regimens.

Unlocking mechanisms

The SARS-CoV-2 coronavirus (also known as 2019-nCoV), responsible for COVID-19, causes infections by entering the lungs. Viruses enter the bronchi in droplets produced by an adjacent infected person, such as by sneezing.

Here, the virus searches out certain protein receptors on lung cells. The virus is covered in a crown of spikes. These spike proteins attach to lung cells to enable the entry of the genetic material of the virus into the cells.

The viral genetic material then immediately hijacks the molecular machines inside the lung cells to reproduce itself. As the virus builds up in the bronchi and lungs, coughing passes the virus to people nearby.

Without any vaccine or drugs to combat the viral infection, we must rely on our immune systems to combat the virus; the chronically sick and the elderly are the most compromised immunologically.

How COVID-19 affects the body.

Timely publications

Scientists in Wuhan, China — where the virus originated — characterized the genetic sequence of the new virus found in lungs of their patients. They discovered that SARS-CoV-2 uses the ACE2 receptor on human lung cells to promote its survival, just as the virus behind the 2002 SARS outbreak did. They set up a molecular diagnostic method to monitor virus infection and how long it remained in patients. The researchers also assessed the antibodies patients made against the virus that would eliminate it.

Through the global, free and immediate communication of these results, further discoveries followed. These came from other scientists in China and two groups of U.S.-based scientists, one in Texas and the other in Seattle.

In record time, these different groups were able to visualize the spike protein and its ACE2 receptor in 3D at an atomic level of resolution. Their findings addressed the mechanisms used by the virus to enter our cells. The Seattle group made a further discovery: they found a mutation in the new virus that differed from the 2002 SARS coronavirus.

Scientists from Germany and Austria focused on how the spike protein was processed by the lung cell to enable viral entry. They found a drug that blocks the entry of SARS-CoV-2 into lung cells in laboratory experiments.

These detailed molecular studies are the foundation for how vaccines, antibodies and antiviral drugs can be made.

A further paper in Science may be applicable to the public health challenge of COVID-19. Here, international collaboration among researchers in the United States, Italy and China showed that travel restrictions were less effective when there were difficulties in detecting coronavirus. However, when combined with rigorous isolation protocols, the results were dramatic.

Canadian effort

The Canadian Institutes of Health Research (CIHR), a health research funding agency, has launched a coronavirus research effort.

Canada may consider conducting additional research on health crises as related to recurring viral pandemics.

For example, the new discoveries outlined from the Seattle group above on the new mutation of the spike protein in SARS-CoV-2 virus falls under the expertise of Canada’s own Nabil Seidah, director of the biochemical neuroendocrinology lab at the Clinical Research Institute of Montreal. He is one of the foremost authorities on a class of enzymes known as protein convertases, including known as furin.

Furin is an enzyme that recognizes the mutation on the spike protein discovered by the researchers in Seattle. In collaboration with researchers from France, Seidah has described the functional consequences of the predicted action of the furin enzyme on the new coronavirus. Canada is fortunate to have one of the global authorities for this class of enzymes.

Another is molecular biologist Nahum Sonenberg. He revolutionized the study of viruses with his discovery of how viruses co-opt the machinery in our cells to make proteins. His discovery enabled researchers in Texas to develop a drug now in clinical trials to combat all strains of influenza virus.

Read more: The taming of polio and the challenge of the flu

Further discovery and COVID-19 research funding

A new discovery has shown conclusively that the action of the furin enzyme on SARS- CoV-2 is essential to enable viral entry into human lung cells in the laboratory and that furin is a potential target for therapeutic intervention.

A further discovery has highlighted the importance of the co-option of the machinery to make new proteins by SARS-CoV2, with a drug that targets the infected cell’s specific protein synthesis initiation factor known as eIF4A. The drug inhibited viral entry into monkey cells in the lab.

Both of these recent discoveries are related to the fundamental discovery research of Seidah and Sonenberg, respectively.

Seidah and Sonenberg were funded by the CIHR through the Foundation Grant Program. Amazingly, the Foundation program was terminated, despite the recommendation from CIHR’s own commissioned report.

A transition plan set up by CIHR to address the loss of funding to our health research leaders will fragment the research.

It may not be in Canada’s best interest to eliminate our most talented researchers when health and disease challenges are at their highest.

John Bergeron gratefully acknowledges Kathleen Dickson as co-author.

This is an updated version of an article originally published March 24, 2020. The new version reflects the fact that Canadian scientists Nabil Seidah and Nahum Sonenberg are eligible for funding for the new grants for COVID-19 research, which was not the case when the article was originally published.

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