The couple, either postdoctoral researchers with Dr. Craig McCormick, were reading an approved drug already used to treat other diseases, such as cancer and irritable bowel syndrome. TG: strangely effective in inhibiting influenza virus replication in the laboratory.
However, when they finished this work, the World Health Organization declared the COVID-19 pandemic, prompting widespread closures that closed labs and put some on hold in establishments around the world.
Exceptions have been made for some highly transmissible and potentially fatal SARS-CoV-2 researchers and other coronaviruses.
“That’s when we decided, ‘We want to test this antiviral that we’ve opposed to flu in coronaviruses,'” Dr. Duguay says in the lab’s bright, busy dining room. -TG immediately and it worked immediately. “
A “surprising result”
Drs. Duguay and Pringle, along with their colleagues in McCormick’s lab, received permission to return to their lab in March 2020 and began investigating how 6-TG would work in bloodless coronavirus strains, such as OC43 and 229E.
Like scientists around the world, they sought to perceive whether the repurposing of existing drugs can be a safe and effective remedy for COVID-19. They were curious to receive more information about how coronaviruses interact with human host cells and where addictions are located, which may only assist in identifying where their weaknesses might lie.
Finally, they discovered a new effect, or mechanism of action, for 6-TG. In mobile culture experiments, they found that the drug can inhibit the replication of human coronaviruses by adding SARS-CoV-2. It does this by interfering with the progression of spike proteins of virus characteristics, which are necessary to enter the host mobile and cause infection. Without them, viruses like SARS-CoV-2 cannot interact with the host mobile or spread.
“One of the main effects of the remedy with this drug is that it inhibits the ability of the virus to produce many spiked proteins and incorporate them into new offspring or baby viruses, so the baby viruses that are produced do not have spikes and therefore cannot cause an infection,” says Dr. McCormick. virologist and professor in the Department of Microbiology and Immunology at Dal.
“It’s an amazing result. “
Dr. Pringle explains that the spikes are glycosylated, meaning they are covered in sugars. These sugar viruses evade the immune formula by protecting the spike from antibodies.
“What we found is that the antiviral 6-TG inhibits glycosylation, so the spike doesn’t get sugar and doesn’t paint,” he says.
Buffering the virus
The researchers, whose findings were described in a recent paper, were bloodless coronaviruses and colleagues they worked with at the universities of Saskatchewan and Calgary were comparing the effect of 6-TG on SARS-CoV-2. They measured the amount of virus produced through a virus-infected mobile phone compared to a mobile phone treated with the drug. The amount of replication on the treated mobile was incredibly low.
“That’s what an antiviral needs to do: it needs it to attenuate the amount of virus produced so that it spreads less efficiently, fewer other people have health problems, and those who have health problems have fewer health problems,” says Dr. Brown. Duguay.
The team is working with Dalhousie’s medical chemist and neurologist, Dr. Sultan Darvesh, to better understand how the drug works and how progress can be made to better target SARS-CoV-2. It conducts computer studies on how the drug interacts with proteins. on mobile. The is which of the many proteins in the host mobile the drug affects.
“It can be like looking for a needle in a haystack,” Dr. Darvish says. “We need to see which of those proteins is to blame for allowing the virus to access cells, and once we locate that protein, we can use the same computational strategies to see if we can make a better drug than 6-TG. “
“I’m very positive about this drug. “
The researchers note that they do not inspire other people to take 6-TG and that there is no evidence to date that other people who take it for other reasons have any advantage in treating COVID-19. This discovery is a vital first step in a lengthy process that can take years to produce a remedy for long-term coronavirus outbreaks.
“Antivirals have a real role to play in viruses over the long term,” says Dr. McCormick. “What I’m pleased about is that we’re giving birth to a new domain that may simply be a new branch of this type of research, where we’re demonstrating that this organization of human proteins are smart targets and play a role in replication. “
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