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Drug strategies to fight COVID-19 move beyond guesses

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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.”

Edited BY Harry Miller

Resource: – CBC.ca

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Small percentage of Ottawa residents infected with COVID-19: Ottawa Public Health – CTV News Ottawa

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OTTAWA —
Ottawa Public Health is reminding residents that COVID-19 is still circulating in our community, and everyone needs to do their part to help limit the spread of the virus.  

Associate Medical Officer of Health Dr. Brent Moloughney says Ottawa Public Health estimates approximately one per cent of Ottawa residents have been infected with novel coronavirus.

“Through everyone’s actions, we’ve been successful in reducing the number of infections that would have otherwise occurred,” said Dr. Moloughney.

“Overall, we estimate that only a small percentage of Ottawans have been infected with COVID so far, perhaps as low as one per cent but perhaps a bit higher.”

As of Thursday, Ottawa Public Health reported 1,985 laboratory-confirmed cases of COVID-19 in Ottawa, including 248 deaths.

“Regardless of the specific number through, the key implication is that the vast majority of us remain susceptible to infection,” said Dr. Moloughney, noting the new cases reported daily show COVID-19 is still circulating in the community.

“In order to track cases within Ottawa and to limit transmission, please seek testing if you think you may be infected with the virus.”

The Ontario Government announced in May that asymptomatic residents of Ontario could present for COVID-19 testing.  Ottawa Public Health says residents can visit the COVID-19 Assessment Centre at Brewer Arena and the two COVID-19 care clinics for testing.

Medical Officer of Health Dr. Vera Etches says the data from the expanded testing criteria has been “educational” as more people present for COVID-19 testing.

“What we’ve found was as the number of people tested grew, we didn’t find a lot more cases. That per cent positivity hasn’t grown,” said Dr. Etches.

“It’s telling us that population out there without symptoms, the general population, may not be where we’re going to find most of our cases.”

The medical officer of health says Ottawa Public Health and health officials in eastern Ontario will test all staff in long-term care homes twice in June.  That would be 8,000 COVID-19 tests this month.

“Our goal is to use all of the testing capacity we have,” said Dr. Etches, adding Ottawa Public Health will look to “test in a smart way”, including workplaces and congregate care settings.

Limit your contacts

With warm weather in the forecast for the weekend, Ottawa Public Health is reminding people to practice physical distancing and limit interactions with people outside your household.

“As more activities become possible, the new normal will be to consider how risky an activity is and how you can reduce the risk of transmission for yourself, your family and others,” said Dr. Moloughney.

“In general, outdoor activities are less risky than indoor ones. The more people that are involved and the closer the contact, the higher the risk.”

Ottawa Public Health has issued a graphic looking at “least safe options” and “safer options” for activities during the COVID-19 pandemic.

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Coronavirus: Two new cases in Winnipeg Friday brings total to 300 – Globalnews.ca

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This story will be updated as the press conference continues.

Two new cases of the novel coronavirus were announced Friday, both of them in Winnipeg.

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The latest cases include one man in his 20s, and another in his 30s, according to the province. One is a truck driver, and the other man was a close contact.

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As of Thursday an additional 671 laboratory tests for the virus were performed. The total number of tests performed since early February is now 47,372.

“Each Manitoban is going to have to decide the level of risk they’re going to take [going forward],” said Dr. Brent Roussin, Manitoba’s chief provincial health officer.

But people who are sick should still stay home, he said.

Roussin added workplaces need to look at their policies and practices when it comes to staying home because they’re ill.

“We need to make it easy as possible … the alternative is people come to work sick.”

Lanette Siragusa reminded people that hospitals and health care centres will start allowing a designated visitor, but some may not start until Monday or later.

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Shared Health’s Chief Nursing Officer said people should call before they go.


READ MORE:
Safety officers heading to Manitoba beaches amid COVID-19, no new cases reported Thursday

© 2020 Global News, a division of Corus Entertainment Inc.

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COVID-19 roundup: new case reported in Owen Sound Friday – Owen Sound Sun Times

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This undated transmission electron microscope image shows SARS-CoV-2, also known as novel coronavirus, the virus that causes COVID-19, isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like.

Photo supplied

One new case of COVID-19 was reported in the region Friday according to the Grey Bruce Health Unit’s daily situation report.

The most recent case was reported in Owen Sound, according to the health unit’s data.

Eighty-eight of the region’s 98 total cases have recovered. None of the active cases are currently hospitalized, and no deaths have been attributed to COVID-19 locally.

Twenty-four cases of the disease have been reported in healthcare workers. No local long-term care or retirement homes are currently under a declared COVID-19 outbreak.

* * *

The Grey Bruce Health Unit is recommending people use virtual forms of participation such as signing petitions, donating to groups, and learning more about racism and how to address it as anti-racism protests spread throughout the world during the COVID-19 pandemic.

“Racism is a public health issue. Racism, in its many forms, profoundly impacts the health and wellbeing of individuals, families and communities,” said a Grey Bruce Health Unit news release. “We recognize that, at this time, people may want to gather to march and express themselves with respect to supporting efforts to end racism.”

The release did list several considerations for people who must participate in any local rallies including spreading out to maintain proper physical distancing, staying outside, wearing a face covering, and bringing hand sanitizer.

The health unit is asking older adults, the immunocompromised, and those living with vulnerable people who are more susceptible to serious complications should they contract COVID-19, to reconsider the need to be present in a large crowd.

“The Grey Bruce Health Unit has the responsibility to identify risk associated with any public health threat, including COVID-19. We remind people that gatherings increase the risk of transmission of disease,” the release said.

* * *

The Grey Bruce Health Unit is encouraging all municipalities to adopt bylaws restricting the use of beach and waterfront spaces after rescinding the beach closure order enacted on May 14.

However, municipalities in Grey-Bruce can now open beaches fully, allow only walk-through access, or maintain a full closure of the beach.

In a bulletin on their website the health unit recommends people check with their local municipality to confirm the status of the beach, waterfront, and river access points before planning to use them.

Even if some public waterfront spaces do reopen, amenities such as public washrooms, change rooms, and water refill stations may still be closed, a health unit media release explained. Therefore, the health unit is recommending beachgoers bring their own water jug with a spigot, soap and paper towels to wash their hands – or an alcohol-based hand sanitizer.

Public health is recommending people wear a non-medical face mask or face covering in places where proper physical distancing measures cannot be controlled. They’re also recommending people bring reusable water bottles and individual containers for food to prevent sharing, and their own garbage bags.

Public health is asking residents to be patient with visitors and tourists who do not know the local guidance information and to politely inform them what is allowed at local beaches, and the proper guidelines to follow.

“We all want to have an enjoyable summer on our beautiful beaches in the safest and most sustainable way possible. We’re in this together,” the bulletin reads.

* * *

Community lab collections at South Bruce Grey Health Centre’s Chesley and Durham sites will resume on Monday.

Appointments will be required to ensure proper physical distancing for patient safety. Patients can begin booking appointments for June 15 and beyond by calling Patient Registration for Chesley (519-363-2340) or Durham (519-369-2340) between the hours of 7:30 a.m. and 3:30 p.m.

People are asked to have a health card and lab requisition ready when calling. A high volume of calls is expected and some waiting may be necessary, according to an SBGHC media release.

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