Coronaviruses are common viruses, and most of us catch one at some point — they cause about 30% of all common colds. A new accidental discovery could help fight these viruses, even the deadlier, emerging ones.
Coronaviruses are the cause of Middle East Respiratory Syndrome (MERS), which infected about 2000 people and killed over 700 since 2012 and Severe Acute Respiratory Syndrome (SARS) that sickened 8,098 people worldwide and killed 774 in a 2003 outbreak. These viruses have high mortality rates, probably because there are no effective anti-viral therapies for them. These coronaviruses also move unpredictably from animals to infect humans, so we never know which will strike next. But, a treatment for those, and other coronaviruses may be on the horizon.
Scientists investigating a compound to treat Ebola found it has anti-viral activity against SARS and MERS coronaviruses. Compound GS-5734 inhibited the ability of coronavirus to multiply in human airway epithelial cells in a test tube and decreased the amount of virus and improved lung function in mice given SARS in the lab.
Zoonotic infections are those passed to humans from animals. Mammals harbor coronaviruses — not usually becoming infected — and bats carry a variety of them, including the two coronaviruses that cause MERS and SARS.
Scientists believe that over 30 years ago, the MERS virus was passed from bats to camels, and eventually to humans. In about 2002, they think the bats passed the SARS viruses to mammals called palm civets that were traded in open markets and passed their virus to humans there.
Infected people experience fever, cough, and shortness of breath. The virus is thought to be spread by particles from the respiratory tract during coughing and sneezing or contact with infected people.
MERS erupted in the Arabian Peninsula and infected people from other countries who traveled to that region. The first case in the US occurred May 2014 in a person from Indiana who had traveled to Saudi Arabia.
SARS broke out in China in 2002, and the infection quickly spread to other Asian countries. Other countries experienced a small number of cases, including four in the UK, plus a significant outbreak in Toronto, Canada. The outbreak was brought under control in July 2003, assisted by a policy of isolating people suspected of having the infection and screening all air passengers traveling from affected countries for signs of the disease.
The high mortality rates, lack of adequate treatment, and randomness of the zoonotic infections have made outbreaks of coronaviruses something to fear. An effective anti-viral agent could save lives and prevent potential pandemics, an outbreak that can spread across the globe.
Sheahan and the research team were studying an anti-viral compound for use against the Ebola virus when they decided to check if it would also inhibit coronaviruses.
The compound, GS-5734, inhibited MERS replication in human airway epithelial cells in the lab but without harming the cells. The compound showed an ability to inhibit a broad range of coronaviruses. It decreased virus production in human lung cells infected with bat coronaviruses, pre-pandemic bat coronaviruses —those that could cause human infections like MERS and SARS if they jumped from bats to humans — and human coronaviruses.
In mice, when the compound was given one day before or one day after a SARS infection, GS-5734 significantly reduced the amount of virus in their lungs, prevented weight loss associated with the disease, and improved their lung function. When the compound was given two days after infection, the disease was just as severe, but the drug inhibited virus multiplication, giving the mice a chance to fight back.
Overall, our work provides evidence that GS-5734 may protect coronavirus-infected patients from progression to severe disease and could prophylactically protect health care workers in areas with existing endemic MERS-coronavirus and that its broad-spectrum activity may prove valuable when a novel coronavirus emerges in the future.
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