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

New hope for cystic fibrosis

October 19, 2018
A new triple-combination drug treatment being trialled at the Mater Hospital in Brisbane could increase the life expectancy of patients with cystic fibrosis.

Bug guts shed light on Central America Chagas disease

October 18, 2018
In Central America, Chagas disease, or American trypanosomiasis, is spread by the "kissing bug" Triatoma dimidiata. By collecting DNA from the guts of these bugs, researchers reporting in PLOS Neglected Tropical Diseases ...

Rapid genomic sequencing of Lassa virus in Nigeria enabled real-time response to 2018 outbreak

October 18, 2018
Mounting a collaborative, real-time response to a Lassa fever outbreak in early 2018, doctors and scientists in Nigeria teamed up with researchers at Broad Institute of MIT and Harvard and colleagues to rapidly sequence the ...

Researchers cure drug-resistant infections without antibiotics

October 17, 2018
Biochemists, microbiologists, drug discovery experts and infectious disease doctors have teamed up in a new study that shows antibiotics are not always necessary to cure sepsis in mice. Instead of killing causative bacteria ...

Infectious disease consultation significantly reduces mortality of patients with bloodstream yeast infections

October 17, 2018
In a retrospective cohort study conducted at the University of Alabama at Birmingham Division of Infectious Diseases, patients with candidemia—a yeast infection in the bloodstream—had more positive outcomes as they relate ...

How drug resistant TB evolved and spread globally

October 17, 2018
The most common form of Mycobacterium tuberculosis (TB) originated in Europe and spread to Asia, Africa and the Americas with European explorers and colonialists, reveals a new study led by UCL and the Norwegian Institute ...

0 comments

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.