Britons infected with coronavirus are among thousands of patients taking part in a European coronavirus mega-trial of four experimental therapies.  

The trial, called Discovery, includes 3,200 patients who have been hospitalised from the killer virus in the UK, Spain, Germany, France, Sweden and Luxembourg. 

It will test the effectiveness of four treatments, including a course of the anti-malaria drug chloroquine, Ebola medication remdesivir and HIV tablets lopinavir/ritonavir.

The AIDS drugs will be trialled with and without an injection of a multiple sclerosis drug known as interferon beta.

The drugs were selected after ‘showing promise’ in early studies in China’s epicentre Wuhan at the peak of the COVID-19 outbreak. 

There are currently no approved treatments or preventive vaccines for COVID-19 and most current patients receive only supportive care such as breathing assistance.

Global infections have now soared past 300,000, with researchers around the world now scrambling to work on new treatments and develop a vaccine. 

A European coronavirus mega-trial of four experimental drugs is now underway on thousands of patients. The anti-malaria drug chloroquine will be one of the treatments tested

A European coronavirus mega-trial of four experimental drugs is now underway on thousands of patients. The anti-malaria drug chloroquine will be one of the treatments tested

Ebola medication remdesivir - touted as a potential coronavirus cure by Donald Trump - will also be trialled

Ebola medication remdesivir – touted as a potential coronavirus cure by Donald Trump – will also be trialled

The scientists behind the Discovery trial say its strength is that drugs can be swapped out if they don’t work and replaced with promising new ones highlighted in the latest research.

Florence Ader, a professor in infectious diseases at Lyon University who is leading the trial, said: ‘We analysed data from the scientific literature on SARS and MERS coronaviruses and the first publications on SARS-COV2 from China in order to come up with a list of antiviral molecules to be tested.

‘[They include] remdesivir, lopinavir and ritonavir in combination, the latter being administered with or without interferon beta and hydroxychloroquine.

‘The list of these potential drugs is also based on the subset of experimental treatments classified as top priorities by the World Health Organization (WHO).

‘The great strength of this trial is its “adaptive” nature. This means that ineffective experimental treatments can very quickly be dropped and replaced by other molecules that emerge from research efforts. 

Lopinavir/ritonavir, marketed as Kaletra (shown), is an anti-HIV medicine given to people living with the virus to prevent it developing into AIDS. It is a class of drug called a protease inhibitor, which essentially stick to an enzyme on a virus which is vital to the virus reproducing

Lopinavir/ritonavir, marketed as Kaletra (shown), is an anti-HIV medicine given to people living with the virus to prevent it developing into AIDS. It is a class of drug called a protease inhibitor, which essentially stick to an enzyme on a virus which is vital to the virus reproducing

In the Discovery trial, the HIV tablets will also be trialled as a combined treatment with interferon beta 1a, a naturally occurring antiviral protein. The molecule forms part of the lungs' own defence mechanism to fight off viruses

In the Discovery trial, the HIV tablets will also be trialled as a combined treatment with interferon beta 1a, a naturally occurring antiviral protein. The molecule forms part of the lungs’ own defence mechanism to fight off viruses

Scientists fear UK won’t get any supplies of promising coronavirus drug remdesivir ‘any time soon’ after pharmaceutical firm puts access on hold 

based on derek gatherer quote and that link from earlier about gilead 

‘We will therefore be able to make changes in real time, in line with the most recent scientific data, in order to find the best treatment for our patients.’ 

Chloroquine is an anti-malarial drug which works by stopping parasites from replicating inside the body, and could stop the coronavirus by making the inside of a cell too dangerous for a virus to enter.

Two versions of it – chloroquine phosphate and hydroxychloroquine – were on a list of drugs which the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has banned companies from buying with the intention of exporting them.

Meanwhile the Wuhan Institute of Virology – in the city where the crisis began – claimed the drug was ‘highly effective’ in petri dish tests.

One report has claimed officials in the Netherlands already suggest treating critically-ill patients with the drug.

And doctors in South Korea and China both say the drug is an ‘effective’ antiviral treatment against the disease, according to a report by US virologists. 

The drug is cheap, safe and readily available to buy over the counter in the UK as travel medicine – a two-week supply costs just £3.22 from Boots.

Remdesivir has been touted by Donald Trump and credited with helping in the recovery of a 79-year-old Italian man who had the disease. 

The promising anti-viral drug works by neutralising a vital enzyme viruses use to reproduce. It is called a RNA polymerase inhibitor.

It was developed 10 years ago by California-based drug firm Gilead Sciences, with the intention of it destroying the Ebola virus.

It effectively treated monkeys infected with Ebola, according to the US National Institutes of Health. But it had little success on humans.

However, it remains a functional antiviral drug which, in lab conditions, can destroy a variety of viruses. Researchers from the Wuhan Institute of Virology in China said it was ‘highly effective’ against the COVID-19 coronavirus. 

Doctors in the US have tried it on patients and it managed to speed up the recovery of the first person to be treated for the virus there.

The a 35-year-old man in Washington state, close to Seattle – whose infection was announced on January 20 – recovered after being given the drug.

Coronavirus cure hopes were further raised after an infected Italian man in his 70s recovered with the help of the experimental Ebola drug.

Doctors gave the unidentified 79-year-old remdesivir. Officials in Liguria – the coastal region where the patient lives, which is south of Milan – announced he had recovered and could go home after 12 days in hospital.

The drug also showed success in a critically-ill woman in the US and 14 Americans who tested positive for the coronavirus after catching it on the Diamond Princess cruise ship.   

Lopinavir/ritonavir, marketed as Kaletra and Aluvia, is an anti-HIV medicine given to people living with the virus to prevent it developing into AIDS. 

It is a class of drug called a protease inhibitor, which essentially stick to an enzyme on a virus which is vital to the virus reproducing. 

By doing this it blocks the process the virus would normally use to clone itself and spread the infection further. 

A group of patients who were among the first in Australia with confirmed cases of coronavirus were successfully treated using the HIV drugs along with chloroquine. 

Lopinavir and ritonavir, the active drugs in Kaletra, were also tested in China on a group of 199 patients with COVID-19 but the trial found less impressive results.

The study published in the New England Journal of Medicine on March 18 the Chinese researchers gave 99 patients the drug and the remaining standard care over four weeks. 

‘In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care,’ the study concluded. 

The study found both groups took 16 days to see clinical improvement.  

However, the study did find those treated with Kaletra spent less time in intensive care – 6 days compared to 11 days for the control group. 

The study also found a small group patients treated with the drug within 12 days of developing symptoms did appear to show improvement over standard care. 

About 35 companies and academic institutions are also working to create a vaccine for COVID-19 as opposed to a treatment. 

In the Discovery trial, the HIV tablets will also be trialled as a combined treatment with interferon beta 1a, a naturally occurring antiviral protein. 

The molecule forms part of the lungs’ own defence mechanism to fight off viruses.

Doctors believe giving more of this molecule to the lung could help reduce the severity of infection with COVID-19. 

Flu, anti-malaria, arthritis and HIV medication: The promising therapies being tested on coronavirus patients around the world – but how many are the NHS trying?   

NHS hospitals are coming under growing pressure to use experimental drugs to try and treat patients infected with the coronavirus.

Doctors and pharmaceutical firms around the world are scrambling to find a drug that can stop the deadly virus, which has now killed more than 8,200 people.

Medicines already in use for conditions ranging from HIV to rheumatoid arthritis, malaria, the flu and even Ebola are serious contenders and are being tested to see how they could help patients infected with COVID-19.

The Government has refused to confirm if any are being tested out on the 2,626 coronavirus patients in the UK – the NHS advises anyone with troublesome symptoms to take paracetamol and rest at home unless they feel life-threateningly ill.

But its medicines regulator last month banned companies from exporting three drugs – for HIV and malaria – in a bid to protect the UK’s stocks of them.

All three have been used in experimental treatments by doctors in China, raising the prospect of Britain doing the same.

Here, MailOnline reveals some of the drugs that experts believe have potential.

Chloroquine phosphate (Malaria) 

One drug being used by doctors fighting the coronavirus outbreak is chloroquine phosphate, an anti-malarial medication.

The drug – sold under the brand name Arlan – kills malaria parasites in the blood, stopping the tropical disease in its tracks.

But tests of the drug – which has been used for 70 years – on COVID-19 patients in China show it has potential in fighting the life-threatening virus.

One drug being used by doctors fighting the coronavirus outbreak is chloroquine phosphate, an anti-malarial medication. It is sold under the brand name Arlan

One drug being used by doctors fighting the coronavirus outbreak is chloroquine phosphate, an anti-malarial medication. It is sold under the brand name Arlan

Chinese officials claimed the drug ‘demonstrated efficacy and acceptable safety in treating COVID-19 associated pneumonia’.

Experts at the University of Palermo in Italy, as well as a team in Israel, collated the research on the drug in treating the coronavirus.

In their report, they claimed officials in the Netherlands already suggest treating critically-ill patients with the drug.

South Korea and China both say the drug is an ‘effective’ antiviral treatment against the disease, according to a report by US virologists.

The Wuhan Institute of Virology – in the city where the crisis began – claimed the drug was ‘highly effective’ in petri dish tests.

Tests by those researchers, as well as others, showed it has the power to stop the virus replicating in cells, and taking hold in the body.

Twenty-three clinical trials on the drug are already underway on patients in China, and one is planned in the US and another in South Korea.

University of Minnesota experts are planning to test whether the drug – sometimes given to treat lupus and arthritis – prevents the progression of COVID-19.

Chloroquine was prescribed around 46,000 times in 2018 in the UK – but it is also available over-the-counter from pharmacies without a prescription.

Professor Robin May, an infectious disease specialist at Birmingham University, said the safety profile of the drug is ‘well-established’.

He added: ‘It is cheap and relatively easy to manufacture, so it would be fairly easy to accelerate into clinical trials and, if successful, eventually into treatment.’

Professor May suggested chloroquine may work by altering the acidity of the area of cells that it attacks, making it harder for the virus to replicate. 

Hydroxychloroquine (Malaria)

Chinese scientists investigating the other form of chloroquine penned a letter to a prestigious journal saying its ‘less toxic’ derivative may also help.

Hydroxychloroquine, sold under the brand name Plaquenil, may treat COVID-19

Hydroxychloroquine, sold under the brand name Plaquenil, may treat COVID-19

In the comment to Cell Discovery – owned by publisher Nature, they said it shares similar chemical structures and mechanisms.

The team of experts added: ‘It is easy to conjure up the idea that hydroxychloroquine may be a potent candidate to treat infection by SARS-CoV-2.’ 

But the Wuhan Institute of Virology scientists admitted they are still lacking evidence to prove it is as effective as chloroquine phosphate.

Hydroxychloroquine, sold under the brand name Plaquenil, causes side effects such as skin rashes, nausea, diarrhoea and headaches.

Drug giant Sanofi carried out a study on 24 patients, which the French government described as ‘promising’.

Results showed three quarters of patients treated with the drug were cleared of the virus within six days. None of the placebo group were treated.

French health officials are now planning on a larger trial of the drug, which is used on the NHS to treat lupus and rheumatoid arthritis as well as malaria.

Lopinavir/ritonavir (HIV)

Lopinavir/ritonavir, marketed as Kaletra and Aluvia, is an anti-HIV medicine given to people living with the virus to prevent it developing into AIDS.

Lopinavir/ritonavir, marketed under the brand names Kaletra and Aluvia, is an anti-HIV medicine

Lopinavir/ritonavir, marketed under the brand names Kaletra and Aluvia, is an anti-HIV medicine

The drug has shown promise as a way of tackling coronavirus, scientists say, because it is able to bind to the outside of the coronavirus.

It is a class of drug called a protease inhibitor, which essentially stick to an enzyme on a virus which is vital to the virus reproducing. By doing this it blocks the process the virus would normally use to clone itself and spread the infection further.

In a clinical trial application submitted in the US from Asan Medical Center, in Seoul, South Korea, scientists said: ‘In vitro [laboratory] studies revealed that lopinavir/ritonavir [has] antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).’

Chinese media reported that the drug was successfully used to cure patients with the coronavirus, but the reports have not been scientifically proven.

US-based manufacturer AbbVie has donated free supplies of Kaletra to health authorities in China, the US and Europe – it is not clear whether the UK is included.

The drug is available on the NHS and was prescribed around 1,400 times in 2018, either as Kaletra or ritonavir on its own.

Favipiravir (flu)

Favipiravir is the active ingredient in a flu drug called Avigan which is sold in Japan.

Doctors in China have claimed it was ‘clearly effective’ in patients with the coronavirus after they gave it to 80 people in the cities of Wuhan and Shenzen.

Favipiravir is the active ingredient in a flu drug called Avigan which is sold in Japan

Favipiravir is the active ingredient in a flu drug called Avigan which is sold in Japan

They said it sped up patients’ recovery, reduced lung damage and did not cause any obvious side effects. It is also used to treat yellow fever and foot-and-mouth.

According to local media, patients who were given the medicine in Shenzhen had negative results for the coronavirus an average of four days after being diagnosed.

This compared with 11 days for those who were not treated with the drug. It is not clear what the results were of the trials in Wuhan, the worst-hit part of China.

The drug is an anti-viral medication which neutralises a vital enzyme that viruses use to reproduce. It is called a RNA polymerase inhibitor.

It is not used by the NHS. It’s produced by the Japanese company Fujifilm Toyama Chemical.

Remdesivir (Ebola)

Remdesivir is an anti-viral drug that works in essentially the same way as favipiravir – by crippling the RNA polymerase enzyme, stopping a virus from reproducing.

It was developed around 10 years ago by the pharmaceutical company Gilead Sciences with the intention of it destroying the Ebola virus. It was pushed aside, however, when other, better candidates emerged.

Remdesivir is an anti-viral drug that works in essentially the same way as favipiravir – by crippling the RNA polymerase enzyme, stopping a virus from reproducing

Remdesivir is an anti-viral drug that works in essentially the same way as favipiravir – by crippling the RNA polymerase enzyme, stopping a virus from reproducing

But it remained an anti-viral drug with the ability to destroy various viruses in lab tests, scientists said. Doctors in the US tried it on three hospitalised coronavirus patients but results were mixed.

The drug is now being trialled on coronavirus patients in China and at the University of Nebraska, CNN reports.

Doctors writing in a study led by the Wuhan Institute of Virology, published in the prestigious scientific journal Nature last month, said: ‘Our findings reveal that remdesivir [is] highly effective in the control of 2019-nCoV infection in vitro.’

They added that, since the drug is proven to be safe in humans, it ‘should be assessed in human patients suffering from the novel coronavirus disease’.

Remdesivir is not prescribed on the NHS. 

Sarilumab (Rheumatoid arthritis)

Sarilumab, a rheumatoid arthritis drug which is marketed as Kevzara in the US, is set to be trialled on patients in the US

Sarilumab, a rheumatoid arthritis drug which is marketed as Kevzara in the US, is set to be trialled on patients in the US

Sarilumab, a rheumatoid arthritis drug which is marketed as Kevzara and is available to be prescribed on the NHS, is set to be trialled on patients in the US.

Pharmaceutical companies Sanofi and Regeneron plan to give the medication to people with the coronavirus to see if it can help calm their immune response.

The drug works by blocking part of the immune system which can cause inflammation, or swelling, which is overactive in people with rheumatoid arthritis.

WHAT DO WE KNOW ABOUT THE CORONAVIRUS?

What is the coronavirus? 

A coronavirus is a type of virus which can cause illness in animals and people. Viruses break into cells inside their host and use them to reproduce itself and disrupt the body’s normal functions. Coronaviruses are named after the Latin word ‘corona’, which means crown, because they are encased by a spiked shell which resembles a royal crown.

The coronavirus from Wuhan is one which has never been seen before this outbreak. It has been named SARS-CoV-2 by the International Committee on Taxonomy of Viruses. The name stands for Severe Acute Respiratory Syndrome coronavirus 2.

Experts say the bug, which has killed around one in 50 patients since the outbreak began in December, is a ‘sister’ of the SARS illness which hit China in 2002, so has been named after it.

The disease that the virus causes has been named COVID-19, which stands for coronavirus disease 2019.

Dr Helena Maier, from the Pirbright Institute, said: ‘Coronaviruses are a family of viruses that infect a wide range of different species including humans, cattle, pigs, chickens, dogs, cats and wild animals. 

‘Until this new coronavirus was identified, there were only six different coronaviruses known to infect humans. Four of these cause a mild common cold-type illness, but since 2002 there has been the emergence of two new coronaviruses that can infect humans and result in more severe disease (Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses). 

‘Coronaviruses are known to be able to occasionally jump from one species to another and that is what happened in the case of SARS, MERS and the new coronavirus. The animal origin of the new coronavirus is not yet known.’ 

The first human cases were publicly reported from the Chinese city of Wuhan, where approximately 11million people live, after medics first started publicly reporting infections on December 31.

By January 8, 59 suspected cases had been reported and seven people were in critical condition. Tests were developed for the new virus and recorded cases started to surge.

The first person died that week and, by January 16, two were dead and 41 cases were confirmed. The next day, scientists predicted that 1,700 people had become infected, possibly up to 7,000. 

Where does the virus come from?

According to scientists, the virus almost certainly came from bats. Coronaviruses in general tend to originate in animals – the similar SARS and MERS viruses are believed to have originated in civet cats and camels, respectively.

The first cases of COVID-19 came from people visiting or working in a live animal market in Wuhan, which has since been closed down for investigation.

Although the market is officially a seafood market, other dead and living animals were being sold there, including wolf cubs, salamanders, snakes, peacocks, porcupines and camel meat. 

A study by the Wuhan Institute of Virology, published in February 2020 in the scientific journal Nature, found that the genetic make-up virus samples found in patients in China is 96 per cent identical to a coronavirus they found in bats.

However, there were not many bats at the market so scientists say it was likely there was an animal which acted as a middle-man, contracting it from a bat before then transmitting it to a human. It has not yet been confirmed what type of animal this was.

Dr Michael Skinner, a virologist at Imperial College London, was not involved with the research but said: ‘The discovery definitely places the origin of nCoV in bats in China.

‘We still do not know whether another species served as an intermediate host to amplify the virus, and possibly even to bring it to the market, nor what species that host might have been.’  

So far the fatalities are quite low. Why are health experts so worried about it? 

Experts say the international community is concerned about the virus because so little is known about it and it appears to be spreading quickly.

It is similar to SARS, which infected 8,000 people and killed nearly 800 in an outbreak in Asia in 2003, in that it is a type of coronavirus which infects humans’ lungs. It is less deadly than SARS, however, which killed around one in 10 people, compared to approximately one in 50 for COVID-19.

Another reason for concern is that nobody has any immunity to the virus because they’ve never encountered it before. This means it may be able to cause more damage than viruses we come across often, like the flu or common cold.

Speaking at a briefing in January, Oxford University professor, Dr Peter Horby, said: ‘Novel viruses can spread much faster through the population than viruses which circulate all the time because we have no immunity to them.

‘Most seasonal flu viruses have a case fatality rate of less than one in 1,000 people. Here we’re talking about a virus where we don’t understand fully the severity spectrum but it’s possible the case fatality rate could be as high as two per cent.’

If the death rate is truly two per cent, that means two out of every 100 patients who get it will die. 

‘My feeling is it’s lower,’ Dr Horby added. ‘We’re probably missing this iceberg of milder cases. But that’s the current circumstance we’re in.

‘Two per cent case fatality rate is comparable to the Spanish Flu pandemic in 1918 so it is a significant concern globally.’

How does the virus spread?

The illness can spread between people just through coughs and sneezes, making it an extremely contagious infection. And it may also spread even before someone has symptoms.

It is believed to travel in the saliva and even through water in the eyes, therefore close contact, kissing, and sharing cutlery or utensils are all risky. It can also live on surfaces, such as plastic and steel, for up to 72 hours, meaning people can catch it by touching contaminated surfaces.

Originally, people were thought to be catching it from a live animal market in Wuhan city. But cases soon began to emerge in people who had never been there, which forced medics to realise it was spreading from person to person. 

What does the virus do to you? What are the symptoms?

Once someone has caught the COVID-19 virus it may take between two and 14 days, or even longer, for them to show any symptoms – but they may still be contagious during this time.

If and when they do become ill, typical signs include a runny nose, a cough, sore throat and a fever (high temperature). The vast majority of patients will recover from these without any issues, and many will need no medical help at all.

In a small group of patients, who seem mainly to be the elderly or those with long-term illnesses, it can lead to pneumonia. Pneumonia is an infection in which the insides of the lungs swell up and fill with fluid. It makes it increasingly difficult to breathe and, if left untreated, can be fatal and suffocate people.

Figures are showing that young children do not seem to be particularly badly affected by the virus, which they say is peculiar considering their susceptibility to flu, but it is not clear why. 

What have genetic tests revealed about the virus? 

Scientists in China have recorded the genetic sequences of around 19 strains of the virus and released them to experts working around the world. 

This allows others to study them, develop tests and potentially look into treating the illness they cause.   

Examinations have revealed the coronavirus did not change much – changing is known as mutating – much during the early stages of its spread.

However, the director-general of China’s Center for Disease Control and Prevention, Gao Fu, said the virus was mutating and adapting as it spread through people.

This means efforts to study the virus and to potentially control it may be made extra difficult because the virus might look different every time scientists analyse it.   

More study may be able to reveal whether the virus first infected a small number of people then change and spread from them, or whether there were various versions of the virus coming from animals which have developed separately.

How dangerous is the virus?  

The virus has a death rate of around two per cent. This is a similar death rate to the Spanish Flu outbreak which, in 1918, went on to kill around 50million people.

Experts have been conflicted since the beginning of the outbreak about whether the true number of people who are infected is significantly higher than the official numbers of recorded cases. Some people are expected to have such mild symptoms that they never even realise they are ill unless they’re tested, so only the more serious cases get discovered, making the death toll seem higher than it really is.

However, an investigation into government surveillance in China said it had found no reason to believe this was true.

Dr Bruce Aylward, a World Health Organization official who went on a mission to China, said there was no evidence that figures were only showing the tip of the iceberg, and said recording appeared to be accurate, Stat News reported.

Can the virus be cured? 

The COVID-19 virus cannot be cured and it is proving difficult to contain.

Antibiotics do not work against viruses, so they are out of the question. Antiviral drugs can work, but the process of understanding a virus then developing and producing drugs to treat it would take years and huge amounts of money.

No vaccine exists for the coronavirus yet and it’s not likely one will be developed in time to be of any use in this outbreak, for similar reasons to the above.

The National Institutes of Health in the US, and Baylor University in Waco, Texas, say they are working on a vaccine based on what they know about coronaviruses in general, using information from the SARS outbreak. But this may take a year or more to develop, according to Pharmaceutical Technology.

Currently, governments and health authorities are working to contain the virus and to care for patients who are sick and stop them infecting other people.

People who catch the illness are being quarantined in hospitals, where their symptoms can be treated and they will be away from the uninfected public.

And airports around the world are putting in place screening measures such as having doctors on-site, taking people’s temperatures to check for fevers and using thermal screening to spot those who might be ill (infection causes a raised temperature).

However, it can take weeks for symptoms to appear, so there is only a small likelihood that patients will be spotted up in an airport.

Is this outbreak an epidemic or a pandemic?   

The outbreak was declared a pandemic on March 11. A pandemic is defined by the World Health Organization as the ‘worldwide spread of a new disease’. 

Previously, the UN agency said most cases outside of Hubei had been ‘spillover’ from the epicentre, so the disease wasn’t actually spreading actively around the world.



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