A drug that’s been used for more than a decade to treat cancer could cure people with Covid-19, according to a new study.
The drug, called pralatrexate, is a chemotherapy medication that was originally developed to treat lymphomas – tumours that originate in the glands.
Chinese researchers found pralatrexate outperforms remdesivir, which is currently the leading anti-viral medication used to treat Covid-19 patients.
Pralatrexate was approved by the US Food and Drug Administration in 2009 for patients with terminal disease in spite of its toxicity.
Adverse effects of pralatrexate include fatigue, nausea and mucositis – inflammation and ulceration of the mucous membranes lining the digestive tract.
However, repurposing pralatrexate in a way that eliminates its side effects shows much potential, according to researchers.
Colourised scanning electron micrograph of an apoptotic cell (pink) heavily infected with SARS-COV-2 virus particles (green), isolated from a patient sample. pralatrexate, a chemotherapy medication originally developed to treat lymphoma, could potentially be repurposed to treat Covid-19
‘Identifying effective drugs that can treat Covid-19 is important and urgent, especially the approved drugs that can be immediately tested in clinical trials,’ say the study authors, led by Dr Haiping Zhang at the Shenzhen Institutes of Advanced Technology, China.
‘Our study discovered that pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than remdesivir within the same experimental conditions.’
Following the global outbreak of Covid-19, researchers were inspired by the idea of repurposing existing drugs that were originally developed to treat other conditions.
Remdesivir was initially developed to treat hepatitis C and then repurposed as a potential Ebola treatment, Due to the similarity in the structures of these viruses to SARS-CoV-2, the virus which causes Covid-19, experts hoped it may be able to help fight the current pandemic
US BOUGHT ALMOST ENTIRE GLOBAL SUPPLY OF REMDESIVIR IN JUNE
Boris Johnson was forced in July allay fears of an anti-coronavirus drugs shortage today after Donald Trump bought up almost the entire global supply of remdesivir.
The US president was accused of ‘undermining’ the global coronavirus fight by splashing the cash on one of only two drugs approved to treat Covid-19 at the time.
UK business minister Nadhim Zahawi was among those who criticised his decision to make the rest of the world compete for the medication, originally designed to treat Ebola but proven to speed up recovery time for coronavirus patients.
But Downing Street and the Department of Health later played down the significance of the move, insisting that the UK has enough of a stockpile to treat everyone who needs it.
The Prime Minister’s official spokesman said on July 1: ‘The UK currently has a sufficient stock of Remdesivir.’
And the Department of Health said it had secured supplies in advance and had enough to treat every NHS patient who needs it.
The US Department of Health and Human Services (HSS) had earlier revealed it had secured more than 500,000 treatment courses of remdesivir for American hospitals.
It represents the entire global supply for July and 90 per cent of stocks for August and September, leading to fears of an autumn shortage.
Discussing the deal — which US health chiefs boasted was ‘amazing’ — Mr Zahawi told Sky News: ‘It’s much better to work together than to work to undermine each other, so we’ll continue in that spirit.’
Artificial intelligence can help identify such drugs by simulating how different drugs would interact with SARS-CoV-2, the virus that causes Covid-19.
To aid virtual screening of existing drugs, Zhang and colleagues combined multiple computational techniques that simulate drug-virus interactions.
They used this hybrid approach to screen 1,906 existing drugs for their potential ability to inhibit replication of SARS-CoV-2 by targeting a viral protein called RNA-dependent RNA polymerase (RdRP).
RdRP is an essential protein encoded in the genomes of all RNA-containing viruses, such as SARS-CoV-2.
The novel screening approach identified four promising drugs, which were then tested against SARS-CoV-2 in lab experiments.
Two of the drugs, pralatrexate and azithromycin, successfully inhibited replication of the virus.
Further lab experiments showed that pralatrexate more strongly inhibited viral replication than remdesivir, suggesting the former could potentially be repurposed for Covid.
However, this chemotherapy drug can prompt significant side effects and, as it is used for people with terminal lymphoma, immediate use for Covid-19 patients is not guaranteed.
Despite this, the findings support the use of the new screening strategy to identify drugs that could be tweaked, according to the team.
‘We have demonstrated the value of our novel hybrid approach that combines deep-learning technologies with more traditional simulations of molecular dynamics,’ Dr Zhang said.
The researchers, who have published their work in PLOS Computational Biology are now developing additional computational methods for generating novel molecular structures that could be developed into new drugs to treat Covid-19.
The study follows some general scepticism regarding the efficiency of remdesivir, which was initially developed to treat hepatitis C and then repurposed as a potential Ebola treatment.
After disappointing results treating Ebola in 2014, remdesivir was tested in the early stages of this year’s pandemic.
There is no consensus as to whether it is effective however, with clinical trials showing mixed results.
The NHS has approved it for use on Covid-19 patients in the hope it can help, but are already being forced to ration the drug, which costs £2,400 per course ($3,120).
In November, the World Health Organisation (WHO) said doctors should not treat coronavirus patients with remdesivir ‘regardless of how ill they are’.
Officials at the time said there is ‘no evidence’ it boosts people’s chances of surviving the disease or stops them falling ill enough to need mechanical ventilation’.
They also warned there is the ‘possibility of important harm’ when using the experimental Ebola drug as it can cause kidney and liver damage in some patients.
In December, however, a team of British experts reported in Nature Communications that remdesivir could be a highly effective Covid-19 treatment ‘for some patients’.
It had helped cure a 31-year-old patient who suffered a rare reaction to the disease, due to a genetic disorder called XLA, which prevented him from making antibodies to fight infection.
‘There have been different studies supporting or questioning remdesivir’s effectiveness, but some of those conducted during the first wave of infection may not be optimal for assessing its antiviral properties,’ said study author Dr James Thaventhiran from the MRC Toxicology Unit at the University of Cambridge.
WHAT IS REMDESIVIR AND DOES IT WORK AGAINST CORONAVIRUS?
Remdesivir, an anti-viral drug first made to try and treat Ebola, has been used experimentally on Covid-19 patients since the outbreak’s early days.
The FDA issued an emergency use authorization for the drug on May 1, in response to the preliminary results of a notable study that was released at the end of April.
It was also given the green-light for use on the NHS in Britain at the same time.
There are claims of miraculous recovery, improved survival odds and shorter illness, but other studies have found it makes no difference to patients in hospital with Covid-19.
Remdesivir produced encouraging results earlier this year when it showed promise for both preventing and treating MERS – another coronavirus – in macaque monkeys.
The drug appears to help stop the replication of viruses like coronavirus and Ebola alike.
It’s not entirely clear how the drug accomplishes this feat, but it seems to stop the genetic material of the virus, RNA, from being able to copy itself.
That, in turn, stops the virus from being able to proliferate further inside the patient’s body.