During a press conference on March 19, President Donald Trump talked about the encouraging results of two drugs called chloroquine and hydrochloroquine as treatments for the novel coronavirus, claiming that the medications have “gone through the approval process” and that “we’re going to be able to make that drug available almost immediately.”
But the U.S. Food and Drug Administration (FDA) swiftly issued a statement to clarify that these drugs are not approved as treatments for COVID-19. Both drugs are approved to treat malaria, lupus and rheumatoid arthritis, but must still be assessed in clinical trials before being declared a safe and effective COVID-19 treatment. Doctors in the U.S. have wide latitude to prescribe drugs “off-label,” meaning for conditions beyond their initial FDA approval.
“We understand and recognize the urgency with which we are all seeking prevention and treatment options for COVID-19. FDA staff are working expeditiously on that front,” FDA commissioner Dr. Stephen M. Hahn said in the statement. “We also must ensure these products are effective; otherwise we risk treating patients with a product that might not work when they could have pursued other, more appropriate, treatments.”
So could this drugs treat the novel coronavirus?
Chloroquine earned FDA approval as a malaria treatment in 1949. A 2005 report first published in journal Virology first raised the possibility that Chloroquine and its derivative hydroxychloroquine might be effective at treating COVID-19.The study also revealed that chloroquine could prevent the spread of the SARS-CoV virus as it interferes with the virus’s ability to replicate in two ways. First, the drug enters compartments called endosomes within the cell membrane. Endosomes tend to be slightly acidic, but the chemical structure of the drug boosts their pH, making the compartments more basic. Many viruses, including SARS-CoV, acidify endosomes in order to breach the cell membrane, release their genetic material and begin replication; chloroquine blocks this critical step.
The drug also prevents SARS-CoV from plugging into a receptor called angiotensin-converting enzyme 2, or ACE2, on primate cells, according to the 2005 report. When the virus inserts its spike protein into the ACE2 receptor, it sets off a chemical process that alters the structure of the receptor and allows the virus to infect. An adequate dose of chloroquine appears to undermine this process, and in turn, viral replication in general.
In February, a research group led by virologist Manli Wang of the Chinese Academy of Sciences put the idea to the test and found that chloroquine successfully stopped the spread of SARS-CoV-2 in cultured human cells. Preliminary reports from China, South Korea and France suggest that the treatment is at least somewhat effective in treating human patients, and some hospitals in the U.S. have begun administering the drug. In addition, the FDA is organizing a large clinical trial to formally assess the drug’s effects according to the NY Times.
However, due to a short supply of chloroquine in China, and the fact that an overdose can lead to acute poisoning in humans, Wang’s team also investigated the closely related drug hydroxychloroquine. Though it shares a similar structure, hydroxychloroquine shows lower cell toxicity in animals than chloroquine and remains widely available as a treatment for lupus and rheumatoid arthritis.
Wang’s team tested hydroxychloroquine in primate cells and found that, like chloroquine, the drug prevented SARS-CoV-2 replication, according to a report published March 18 in the journal Cell Discovery. As of Feb. 23, seven clinical trials had been registered in the Chinese Clinical Trial Registry to test the drug’s effectiveness against COVID-19 infection, the authors noted.
In the U.S., the University of Minnesota is studying whether taking hydroxychloroquine can protect people living with infected COVID-19 patients from catching the virus themselves. Both drugs have been in short supply but on March 19 the epharmaceutical company Bayer donated 3 million tablets to the federal goverment. Other companies including Mylan and Teva just to name a few are also moving to make donations.
However there are also a number of setbacks: For instance,when taken in high doses over a prolonged period of time,the drugs can cause a rare eye condition known as retinopathy. In their current form the drugs cannot be taken by those with psoriasis,heart arrhythmia and impaired kidneys or liver.
Assuming the drugs are well tolerated in clinical trials and seem effective at treating COVID-19, the FDA will take measures to increase the nation’s supply.