A possible treatment for COVID-19 and an approach for developing others

March 26, 2020

Science Daily/American Society for Microbiology

SARS-CoV-2, the virus that causes COVID-19 disease is more transmissible, but has a lower mortality rate than its sibling, SARS-CoV, according to a review article published this week in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

In humans, coronaviruses cause mainly respiratory infections. Individuals with SARS-CoV-2 may remain asymptomatic for 2 to 14 days post-infection and some individuals likely transmit the virus without developing disease symptoms.

So far, the most promising compound for treating COVID-19 is the antiviral, remdesivir. It is currently in clinical trials for treating Ebola virus infections.

Remdesivir was recently tested in a non-human primate model of MERS-CoV infection. Prophylactic treatment 24 hours prior to inoculation prevented MERS-CoV from causing clinical disease and inhibited viral replication in lung tissues, preventing formation of lung lesions. Initiation of treatment 12 hours after virus inoculation was similarly effective.

Remdesivir has also shown effectiveness against a wide range of coronaviruses. It has already undergone safety testing in clinical trials for Ebola, thereby reducing the time that would be necessary for conducting clinical trials for SARS-CoV-2.

Nonetheless, much work needs to be done to gain a better understanding of the mechanics of SARS-CoV-2. For example, understanding how SARS-CoV-2 interacts with the host ACE2 receptor -- by which SARS-CoV-2 gains entry into the host (whether human or animal) -- might reveal how this virus overcame the species barrier between animals and humans. This could also lead to design of new antivirals.

Although coronaviruses are common in bats, no direct animal source of the epidemic has been identified to date, according to the report. "It is critical to identify the intermediate species to stop the current spread and to prevent future human SARS-related coronavirus epidemics," the researchers write.

https://www.sciencedaily.com/releases/2020/03/200326124159.htm

Drug meant for Ebola may also work against coronaviruses

Drug meant for Ebola may also work against coronaviruses

Understanding how drugs work is an important step in developing new treatments for COVID-19

February 27, 2020

Science Daily/University of Alberta Faculty of Medicine & Dentistry

Researchers who have discovered why the drug remdesivir is effective in treating the coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) expect it might also be effective for treating patients infected with the new COVID-19 strain.

A group of University of Alberta researchers who have discovered why the drug remdesivir is effective in treating the coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) expect it might also be effective for treating patients infected with the new COVID-19 strain.

"Even if you know a drug works, it can be a red flag if you don't know how it works," said virologist Matthias Götte. "It is reassuring if you know exactly how it works against the target.

"We know the drug works against different coronaviruses, like MERS and SARS, and we know the novel coronavirus is very similar to SARS. So I would say I'm cautiously optimistic that the results our team found with remdesivir and MERS will be similar with COVID-19."

The study, published in the Journal of Biological Chemistry this week, is among the first in Canada to discuss the COVID-19 strain.

Until now, there has not been a published explanation of why remdesivir may work against coronaviruses, said Götte, who added his study is an important step in answering that question.

Developed by Gilead Sciences as a response to the 2014 West African Ebola virus epidemic, remdesivir was first used on a patient with the novel coronavirus earlier this year in the United States.

As reported in the New England Journal of Medicine, the patient was given the drug on the seventh day of illness, and showed marked improvement the following day, with symptoms eventually disappearing altogether. And at a recent press conference in Beijing, the assistant director-general of the World Health Organization, Bruce Alyward, said remdesivir is the only drug available that may have real efficacy against COVID-19.

"What our study showed was that remdesivir essentially mimics one of the natural building blocks for RNA synthesis necessary for genome replication of the virus. Enzymes within the virus are synthesizing the viral RNA genome with these building blocks, but they mix up the bits they need with the drug. Once the drug is incorporated into the growing RNA chain, the virus can no longer replicate,"explained Götte.

He said the next step is to wait for results from ongoing clinical trials with remdesivir, which are expected by the end of April. Even then, that won't be the end of the story, he cautioned.

"It's likely we'll need more than one drug to properly fight emerging diseases like COVID-19, as we have with HIV and hepatitis C virus infections," Götte said.

"Ideally, we will have a couple of drugs because certain strains could be resistant to certain treatments."

Götte's study was supported by grants from the Canadian Institutes of Health Research and the Alberta Ministry of Economic Development, Trade and Tourism through the Major Innovation Fund Program and Antimicrobial Resistance -- One Health Consortium.

https://www.sciencedaily.com/releases/2020/02/200227122123.htm

COVID-19 a reminder of the challenge of emerging infectious diseases

February 28, 2020

Science Daily/NIH/National Institute of Allergy and Infectious Diseases

The emergence and rapid increase in cases of coronavirus disease 2019 (COVID-19), a respiratory illness caused by a novel coronavirus, pose complex challenges to the global public health, research and medical communities, write federal scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and from the Centers for Disease Control and Prevention (CDC). Their commentary appears in The New England Journal of Medicine.

NIAID Director Anthony S. Fauci, M.D., NIAID Deputy Director for Clinical Research and Special Projects H. Clifford Lane, M.D., and CDC Director Robert R. Redfield, M.D., shared their observations in the context of a recently published report on the early transmission dynamics of COVID-19. The report provided detailed clinical and epidemiological information about the first 425 cases to arise in Wuhan, Hubei Province, China.

In response to the outbreak, the United States and other countries instituted temporary travel restrictions, which may have slowed the spread of COVID-19 somewhat, the authors note. However, given the apparent efficiency of virus transmission, everyone should be prepared for COVID-19 to gain a foothold throughout the world, including in the United States, they add. If the disease begins to spread in U.S. communities, containment may no longer be a realistic goal and response efforts likely will need to transition to various mitigation strategies, which could include isolating ill people at home, closing schools and encouraging telework, the officials write.

Drs. Fauci, Lane and Redfield point to the many research efforts now underway to address COVID-19. These include numerous vaccine candidates proceeding toward early-stage clinical trials as well as clinical trials already underway to test candidate therapeutics, including an NIAID-sponsored trial of the experimental antiviral drug remdesivir that began enrolling participants on February 21, 2020.

"The COVID-19 outbreak is a stark reminder of the ongoing challenge of emerging and re-emerging infectious pathogens and the need for constant surveillance, prompt diagnosis and robust research to understand the basic biology of new organisms and our susceptibilities to them, as well as to develop effective countermeasures," the authors conclude.

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Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2020/02/200228142016.htm

Remdesivir prevents MERS coronavirus disease in monkeys

February 13, 2020

Science Daily/NIH/National Institute of Allergy and Infectious Diseases

The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.

The new report from NIH's National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.

MERS-CoV is closely related to the 2019 novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.

Remdesivir has previously protected animals against a variety of viruses in lab experiments. The drug has been shown experimentally to effectively treat monkeys infected with Ebola and Nipah viruses. Remdesivir also has been investigated as a treatment for Ebola virus disease in people.

The current study was conducted at NIAID's Rocky Mountain Laboratories in Hamilton, Montana. The work involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV; those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.

The scientists observed the animals for six days. All control animals showed signs of respiratory disease. Animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage. Animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.

The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and COVID-19, the disease that SARS-CoV-2 causes. Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.

The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also provided support for this study. Gilead Sciences, Inc., developed remdesivir, also known as GS-5734, and collaborated in the research.

MERS-CoV emerged in Saudi Arabia in 2012. Through December 2019, the World Health Organization had confirmed 2,499 MERS-CoV cases and 861 deaths (or about 1 in 3). Because about one-third of MERS-CoV cases spread from infected people being treated in healthcare settings, the scientists suggest that remdesivir could effectively prevent disease in other patients, contacts of patients, and healthcare workers. They also note the drug might help patients who are diagnosed with MERS or COVID-19 if given soon after symptoms start.

https://www.sciencedaily.com/releases/2020/02/200213160128.htm