Broad spectrum antiviral drug inhibits a range of emerging coronaviruses

March 6, 2018, American Society for Microbiology
Credit: CC0 Public Domain

Researchers have long known that RNA viruses called coronaviruses cause the common cold and pneumonia. In the last two decades or so, though, researchers have found that these viruses can jump between animal and human hosts. In recent years, coronaviruses have caused lethal outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that span multiple continents. To date, no retroviral drug has been approved to treat these infections.

"These viruses are poised to cause outbreaks," says molecular virologist Ralph C. Baric at the University of North Carolina at Chapel Hill, "and most emerging viruses are cyclic in nature." In the case of SARS, the coronavirus caused an outbreak that began in 2003 and was eventually controlled through public health efforts. However, many pre-epidemic forms of the are still around. "We need to have broad-based and potent drugs on a shelf to control future epidemics."

This week in mBio, report on GS-5734, a promising experimental broad spectrum antiviral drug. Previous studies on have shown that the drug inhibits strains of SARS and MERS that infect human airways and the , as well as infection by the Ebola virus. The researchers now report that the drug also inhibits murine hepatitis virus, or MHV, which is closely related to several human coronaviruses that can cause , sometimes as severe as SARS. [image: MERS-CoV within the cytoplasm of an infected cell, credit: CDC]

The researchers tested the drug on mini models of human lungs consisting of , collected from lung transplants. Because those cells express the genes and proteins of the airways that are targeted by coronavirus infections, researchers can use them as a facsimile for host tissue, says Baric.

GS-5734 may be useful in treating a wide range of infections caused by coronaviruses, including contemporary and epidemic strains, as well as those that are poised to jump from an animal host to a human in the future, says Baric. He co-led the study with Mark Denison, a pediatrician and infectious disease expert whose lab at Vanderbilt University in Nashville, Tennessee, focuses on coronaviruses. The researchers also collaborated with Gilead Sciences, a biopharmaceutical company that is developing a phase I clinical trial of the drug for people with MERS in Saudi Arabia.

In another new development reported in the paper, the researchers identified how the virus fights back against the drug, which is crucial information for predicting whether an antiviral might be effective in human hosts. Like many antivirals, GS-5734 is a nucleoside analog, a class of drugs that work by inhibiting the replication of the virus. However, because viruses evolve so rapidly, they quickly develop mutations that confer resistance to these drugs. Researchers at Vanderbilt identified the genetic mutations in the coronaviruses triggered by exposure to GS-5723. Those mutations, however, significantly weakened the virus, which suggests that the drug may be effective enough to outpace viral evolution.

"The location being targeted doesn't seem to have much capacity to evolve and escape the effects of the , says Baric. "Drug resistance was very difficult to achieve."

Epidemics caused by emerging coronaviruses can be devastating. During a SARS epidemic that began in Asia in 2003, for example, more than 8,000 people in 29 countries became infected, and 774 died, according to data from the World Health Organization. The WHO also reports that since September 2012, more than 2,000 people in 27 countries have become infected with MERS, and 750 have died from the infection.

Explore further: Antiviral inhibits epidemic SARS, MERS and animal coronaviruses

Related Stories

Antiviral inhibits epidemic SARS, MERS and animal coronaviruses

June 28, 2017
A new antiviral drug candidate inhibits a broad range of coronaviruses, including the SARS and MERS coronaviruses, a multi-institutional team of investigators reports this week in Science Translational Medicine. The findings ...

What exactly is coronavirus?

January 30, 2015
The conflicts in Syria and Iraq are straining public health systems and public health efforts meant to prevent and detect the spread of infectious diseases. This is generating a "perfect storm" of conditions for outbreaks. ...

New coronavirus inhibitor exhibits antiviral activity by blocking viral hijacking of host

May 29, 2014
Since the SARS epidemic in 2003, coronaviruses have been on the watch list for emerging pathogens, and the ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) confirmed that they represent a serious ...

Can bats help humans survive the next pandemic?

November 24, 2017
In 2003, severe acute respiratory syndrome (SARS) infected a total of 8,098 people worldwide. First reported in China, it spread rapidly through more than two dozen countries in North America, South America, Europe and Asia.

New SARS-like virus can jump directly from bats to humans, no treatment available

November 10, 2015
Researchers from the University of North Carolina at Chapel Hill have discovered a new bat SARS-like virus that can jump directly from its bat hosts to humans without mutation. However, researchers point out that if the SARS-like ...

New compound inhibits enzyme crucial to MERS and SARS viruses, with a catch

September 8, 2014
Scientists at the University of Illinois, Chicago, have identified a compound that effectively inhibits an enzyme crucial to the viruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome ...

Recommended for you

A multimodal intervention to reduce one of the most common healthcare-acquired infections

March 16, 2018
Surgical site infections are the most frequent health care-associated infections in developing countries. According to the World Health Organization (WHO), this type of infection can affect up to one-third of surgical patients ...

After infection, herpes lurks in nerve cells, ready to strike—New research reveals what enables the virus to do so

March 15, 2018
Once herpes simplex infects a person, the virus goes into hiding inside nerve cells, hibernating there for life, periodically waking up from its sleep to reignite infection, causing cold sores or genital lesions to recur.

Parasitic worms need their intestinal microflora too

March 14, 2018
Scientists at The University of Manchester have cast new light on a little understood group of worm infections, which collectively afflicts 1 in 4 people, mainly children—in the developing the world.

New imaging approach offers unprecedented views of staph infection

March 14, 2018
Eric Skaar, PhD, MPH, marvels at the images on his computer screen—3-D molecular-level views of infection in a mouse. "I'm pretty convinced that these are the most advanced images in infection biology," said Skaar, Ernest ...

Compound scores key win in battle against antibiotic resistance

March 14, 2018
Researchers at Oregon State University have made a key advance in the fight against drug resistance, crafting a compound that genetically neutralizes a widespread bacterial pathogen's ability to thwart antibiotics.

Helicobacter creates immune system blind spot

March 13, 2018
The gastric bacterium H. pylori colonizes the stomachs of around half the human population and can lead to the development of gastric cancer. It is usually acquired in childhood and persists life-long, despite a strong inflammatory ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.