Doctors are exploring how to attack COVID-19 with antiviral treatments repurposed from HIV and Ebola.
COVID-19 is often mild. But it continues to kill and hospitalize so many that physicians hope repurposing existing antivirals could improve survival andpotential antivirals time people are seriously ill.
No treatments for COVID-19 have been approved for use in Canada outside of clinical trials.
Doctors and scientists are exploring three main ways to mitigate SARS-CoV2 infection, the virus that causes COVID-19, so more patients recover. The strategies are based on how the virus enters our cells and makes copies of itself — a process known as replication.
The experimental antiviral medication remdesivir could be the most high profile example. Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, said in late April that remdesivir shortened recovery time from 15 days without specific treatment, compared with 11 days on average with the drug.
The hope is if remdesivir succeeds in shortening recovery from COVID-19, it will reduce the burden on health-care systems — the goal of broader efforts to flatten the curve.
Viral engine stalls
Matthias Gotte, a professor of medical microbiology and immunology at the University of Alberta, discovered why remedesvir seems to be such a potent antiviral.
He compared the way the virus copies itself to the engine of a car.
“The engine needs gas,” he said, in reference to how COVID-19 infection transmits. With remdesivir, the engine gets diesel and stalls. “The virus stops to replicate and stops to propagate.”
An ampule of the Ebola drug remdesivir is pictured during a news conference at University Hospital Eppendorf in Hamburg, Germany in April. An advantage of repurposing drugs for COVID-19 is more is known about their safety. (Ulrich Perrey/Reuters)
Alan Bernstein, a trained virologist and president and CEO of the non-profit CIFAR, a Canadian-based, global research organization that brings together top researchers to address important questions, previously led a major HIV vaccine effort.
“That’s the attraction of repurposing,” Bernstein said of remdesivir and other antiviral trials. “You already have a drug; you know it’s safe at a certain dose.”
But the remdesivir data Fauci read out hasn’t yet been published. And Canadian doctors await key details such as if the drug in fact improves survival, when it works best, if it will be available in clinical trials in Canada and what it will cost.
The three main antiviral strategies doctors and scientists are exploring are:
Stop the virus’ raison d’etre of copying or replicating its RNA genetic material. These drugs, called polymerase inhibitors, include remdesivir, which has shown antiviral activity against this coronavirus.
Stop the virus from properly building the proteins it needs by blocking the snipping tool it uses to do it. These drugs are called protease inhibitors and include lopinavir and ritonavir, used to treat HIV.
Prevent the virus from entering our cells in the first place.
Using the car analogy, Gotte likened the viral copying enzyme, called polymerase, to a vehicle’s engine.
Bernstein said remdesivir throws a monkey wrench into the virus’s ability to incorporate the RNA building blocks it needs to copy itself.
Remdesivir was intended to treat Ebola, but other treatments worked better for that viral infection.
Dr. Ilan Schwartz is an infectious disease physician at the University of Alberta who is not involved in clinical trials of potential antivirals to fight COVID-19. He’s following their progress.
“We’re cautiously optimistic,” Schwartz said. “We’re certainly not talking about something that is going to have a benefit for everyone.”
Remdesivir and other potential treatments should not be prescribed outside of a clinical trial, he said. More needs to be known about the benefits and risks.
Since remdesivir is given to patients by intravenous infusion, doctors say it’s unlikely to gain widespread use outside of hospitals. Favipiravir, another polymerase inhibitor, that’s given orally, is expected to start testing in a Phase 2 clinical trial in long-term care homes in Ontario this month.
Dr. Ken Milne, chief of staff at South Huron Hospital Association in Exeter, Ont., co-hosted a town hall on potential antivirals for the Canadian Association of Emergency Physicians.
Milne said he’s still looking for high-quality evidence that remdesivir and other potential antivirals to fight COVID-19 offer benefits that are important to patients, such as survival without disability.
“I’m skeptical because the evidence that’s been published so far doesn’t support its routine use,” said Milne, creator of the Skeptics Guide to Emergency Medicine, a podcast and blog geared to those involved in patient care.
Milne said in HIV, antivirals are taken long term to improve quality of life. In contrast, COVID-19 is a short-term illness and most recover. That means the bar for safety and effectiveness differ.
AI meets drug design
Two HIV antivirals called lopinavir and ritonavir are protease inhibitors that are used in combination with other anti-HIV treatments to suppress the virus.
When HIV or SARS-CoV-2 enter a human cell, the virus hijacks the cell’s machinery into making more copies of the virus by co-opting certain polyproteins or chains of proteins.
The antiviral drug remdesivir is showing promise as a COVID-19 treatment in early U.S. clinical trials, though other research hasn’t seen as much success. 1:59
Bernstein, the virologist, said to think of polyproteins as two or three sentences fused together without a period between them.
“The protease inhibitor comes along and snips at the period or snips the polyprotein into three or four smaller proteins. A protease inhibitor blocks the protein that does that snipping,” Bernstein said.
Eric Arts, a professor of microbiology and immunology at Western University in London, Ont., said scientists are better off at this stage of the COVID-19 epidemic than at the start of the HIV epidemic, before the advent of protease inhibitors.
“The field of virology and drug development has advanced so much,” said Arts, who holds a Canada Research Chair in HIV. “It’s day and night. When we were trying to find a drug for HIV 30 years ago, it was a guessing game.”
Patience will pay off
With SARS CoV2, researchers know the structure of the viral proteins down to basically the atom level, Arts said. This knowledge also includes the key protein on the surface of our cells that the virus uses to enter, called the ACE2 receptor.
Some antivirals throw a monkey wrench into how a virus replicates, says Alan Bernstein. (CIFAR)
“We can design molecules that would disrupt that interaction,” Arts said. “Or, and this gets really kind of sci-fi, we can take existing drugs, knowing their structures and then do what we call a computer-aided, AI kind of study and see how those existing drugs may dock and block that interaction.”
Pharmaceutical companies have compound libraries of these molecules that scientists, aided by AI, can sift through for candidates that look like they may work effectively against SARS CoV2.
“It’s a very effective way to find something that works,” Arts said, compared with the conventional drug screening approach of conducting tests in the lab followed by animal models and then a decade of clinical trials in humans.
Che Colpitts, an assistant professor in biomedical and molecular sciences at Queen’s University, is working to find new antiviral strategies against RNA viruses. She uses models that resemble the deadly pathogens, including SARS-CoV-2 and another coronavirus disease, MERS.
Colpitts previously looked at how natural compounds produced by plants and fungi to protect themselves could interfere with viral attachment.
“Everybody is definitely jumping on,” to research SARS-CoV-2, she said. “It’s just a really exciting time.”
Colpitts and physicians who’ve treated COVID-19 say a critical factor for prescribing antivirals is to give them to patients before too much damage has set in.
Until effective treatments exist, people need to continue physical distancing, hand hygiene, cough etiquette and to stay home when sick, public health officials, physicians and researchers say.
“With treatment or something that could be effective and good screening, we can control this disease pretty effectively until we have a vaccine,” Arts said. “It’s just we have to be a little more patient for a little while longer and we will have relief.”
HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.
The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.
Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.
“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”
The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.
A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.
Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.
“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.
Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.
The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.
“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.
This report by The Canadian Press was first published Sept. 11, 2024.
ST. JOHN’S, N.L. – Newfoundland and Labrador‘s chief medical officer is monitoring the rise of whooping cough infections across the province as cases of the highly contagious disease continue to grow across Canada.
Dr. Janice Fitzgerald says that so far this year, the province has recorded 230 confirmed cases of the vaccine-preventable respiratory tract infection, also known as pertussis.
Late last month, Quebec reported more than 11,000 cases during the same time period, while Ontario counted 470 cases, well above the five-year average of 98. In Quebec, the majority of patients are between the ages of 10 and 14.
Meanwhile, New Brunswick has declared a whooping cough outbreak across the province. A total of 141 cases were reported by last month, exceeding the five-year average of 34.
The disease can lead to severe complications among vulnerable populations including infants, who are at the highest risk of suffering from complications like pneumonia and seizures. Symptoms may start with a runny nose, mild fever and cough, then progress to severe coughing accompanied by a distinctive “whooping” sound during inhalation.
“The public, especially pregnant people and those in close contact with infants, are encouraged to be aware of symptoms related to pertussis and to ensure vaccinations are up to date,” Newfoundland and Labrador’s Health Department said in a statement.
Whooping cough can be treated with antibiotics, but vaccination is the most effective way to control the spread of the disease. As a result, the province has expanded immunization efforts this school year. While booster doses are already offered in Grade 9, the vaccine is now being offered to Grade 8 students as well.
Public health officials say whooping cough is a cyclical disease that increases every two to five or six years.
Meanwhile, New Brunswick’s acting chief medical officer of health expects the current case count to get worse before tapering off.
A rise in whooping cough cases has also been reported in the United States and elsewhere. The Pan American Health Organization issued an alert in July encouraging countries to ramp up their surveillance and vaccination coverage.
This report by The Canadian Press was first published Sept. 10, 2024.
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