Scientists are scrambling to find drugs that could counter the symptoms of COVID-19, and over the past few months they have been paying special attention to anti-malarial treatments.

In particular, the drugs chloroquine and hydroxychloroquine – both of which are widely available and can be bought with a prescription from a pharmacy – have been touted as a potential "game changer" in the fight against the novel coronavirus, including by U.S. President Donald Trump. 

However, following the U.S. leader's statement, one person in Arizona died from taking a non-medical version of hydroxychloroquine in an attempt to ward off the virus and the World Health Organization (WHO) has said that, so far, there is no definitive evidence of either drug's effectiveness in fighting COVID-19.

So what do these drugs actually do and and could they be an effective counter to the coronavirus?

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What exactly is chloroquine?

The anti-malarial drug chloroquine is a synthetic form of the naturally occurring quinine, which can be found in the bark of the cinchona plant.

While quinine, first isolated by French chemists in 1820, has been in use for hundreds of years in South America to treat fever, German scientists first created the synthetic form of the drug – chloroquine – in the 1930s for the widespread treatment of malaria.

Because of its success in interrupting malaria's ability to digest a host's blood cells, chloroquine and its sister drug Hydroxychloroquine remain on the World Health Organization's list of essential medicines to this day, and are prescribed for those visiting countries where they are at risk of malaria. 

Hydroxychloroquine has also been employed to treat rheumatology conditions such as arthritis.

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Why are they being used to tackle COVID-19?

According to Adrian van den Hoven, the general director of Medicines for Europe, an association that represents some of Europe's largest pharmaceutical companies: "When you have an outbreak like this, where there's no cure available, what researchers do is they look at existing medicines with similar topologies."

Scientists have focussed on biochemical properties of chloroquine and hydroxychloroquine that show it could be used against some viral infections. These include direct antiviral effects, such as blocking steps needed by certain viruses to replicate, and the ability to suppress production and release of proteins involved in inflammatory complications of several viral diseases.

"For this reason, they're looking at malaria medicine," says Van den Hoven, "but chemists are also looking at medicines used for HIV/AIDS and ebola, so different medicines tackling viruses are being experimented with and now there are real trials to test if they work."

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How are the trials being conducted?

Tests of the drugs' effectiveness in tackling the new coronavirus have been conducted in China, the U.S., France, and Spain, with trials either already taking place or set to start in the UK, Norway and Thailand.

"There's some very, very small studies with very few patients, where doctors have given chloroquine and hydroxychloroquine and then they're reporting what the results are," says Van den Hoven.

"The problem with these studies is that they're so small that in the medicine world that's not considered robust enough to justify putting them on a label, so now different bodies in the U.S., the WHO, and here in Europe are doing what is called randomized clinical trials, a large-scale trial to compare the efficacy of the drug and then determine which one works best."

"They've also tested chloroquine and hydroxychloroquine through what is called in vitro tests, which aren't carried out in humans to see which one seems to have more effect on the virus," adds Van den Hoven.

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"It's claimed that hydroxychloroquine has more efficacy but it's not in humans so it's difficult to see how it works."

The inconclusiveness of the testing is what perhaps prompted the WHO's director-general Tedros Adhanom to stress on Monday that "untested drugs without the right evidence could raise false hope and even do more harm than good."

There is also the question of the drug's effectiveness at different stages of COVID-19. "You need to look if it works at early stages of the disease, does it work at critical stages. There are different factors that will be tested in these clinical trials to see how it works best and that will take some time," said Van den Hoven.

While this would usually take several months, Van den Hoven says that, due to the severity of the coronavirus outbreak and the large number of patients who can be tested in comparison with other diseases, this process could be speeded up.

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How effective have the drugs been to be so far?

Much of the data released so far are preliminary and results have been mixed.

Chinese researchers last month reported trial results showing that using chloroquine to treat COVID-19 patients had clinical and virologic benefits in comparison to patients who did not use the drug. It has since been added as a recommended treatment for the disease in China.

However, this week, the Journal of Zhejiang University reported disappointing results from a 30-patient Shanghai study of hydroxychloroquine. It showed the drug worked no better than standard care for patients with COVID-19.

Initial data released last week from a French trial of 24 patients where researchers used hydroxychloroquine showed that 25 percent of patients given the drug still carried the new coronavirus after six days, compared with 90 percent of patients given a placebo.

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The WHO is now calling for larger-scale, international testing of drugs that can fight COVID-19, calling for a "SOLIDARITY trial, to generate robust, high-quality evidence as fast as possible." 

In the U.S., the University of Minnesota has launched a 1,500-person trial to see whether hydroxychloroquine can prevent or reduce the severity of COVID-19 in people exposed to the virus – including healthcare workers and family members of infected people.

"I think the effective and clear information will be when one of these larger clinical trials is done," says Van den Hoven, pointing to tests that look at much larger case samples. 

"Most likely what they'll do is they'll publish the results rough, which means usually when you do a clinical trial you publish the results, someone checks the results are correct, but probably they'll just publish the results rough and then we'll know fairly quickly what's being seen even if that is not the normal procedure because of the emergency procedure."

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How easy is it to get hold of them?

Last week, Trump stated that chloroquine had been approved for use in treating the coronavirus by the US Food and Drugs Administration (FDA), the organization in charge of medicine licenses in the the U.S., adding that that the drug would be made available almost immediately.  

While the FDA has since refuted Trump's claim, saying that it is yet to approve any treatment for COVID-19, pharmacists have reported the drug has been flying off the shelf in the country, with at least four U.S. state pharmacy boards taking steps to limit prescriptions.

New York governor Andrew Cuomo has gone as far as to procure 70,000 doses of hydroxychloroquine and 750,000 doses of chloroquine for upcoming trials in the state. 

While the drug is yet to be fully certified, the US leader has since clarified that chloroquine had been approved for "compassionate use," where doctors can prescribe the drug to those with life-threatening conditions. 

According to Medicines for Europe's Van den Hoven: "Doctors can prescribe off label, so even though this is not for coronavirus, doctors can nevertheless choose to prescribe this medicine for experimental use."

The question is, should people be taking such drugs before they are signed off by bodies like the WHO?

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How dangerous are these drugs?

"These drugs have side effects so they should be taken in accordance with a prescription from a physician," says Van den Hoven.  

For hydroxychloroquine and chloroquine, side effects include vision loss, heart problems or even death, if used incorrectly. 

Earlier in the week, reports of several chloroquine overdoses in Nigeria led the country's Centre for Disease Control to warn people over Twitter that the "WHO has NOT approved the use of chloroquine for #COVID19 management" and that self-medication could "cause harm" and "lead to death."

"You shouldn't go and take them by yourself," stresses Van den Hoven. "There are also a lot of counterfeit drugs circulating on the internet claiming to be these medicines, which we should be extremely cautious about as illegal websites pop up with promises of cures against coronavirus."

As for whether we will see the widespread circulation of drugs like chloroquine and hydroxychloroquine, Van den Hoven says emphatically that we should focus on advice from medical institutions. 

"Obviously politicians would like to treat their people and make people better, and so they might hear about this drug today and another drug tomorrow, but it's better if this is structured and scientific because you don't want people jumping from drug to drug."

"I'd advise people to follow the recommendations of medical agencies during this time," says Van den Hoven, "groups like the U.S.-based Centre for Disease Control – in Europe we have the European Centre of Disease Control – and not follow the opinions of people who don't have a scientific background."