A drug that has been used for more than a decade to treat cancer can cure people with Covid-19, according to a new study.
The drug, called pralatrexate, is a chemotherapy drug originally developed to treat lymphomas – tumors that originate in the glands.
Chinese researchers have found that pralatrexate outperforms remdesivir, which is currently the main antiviral drug used to treat patients with Covid-19.
Pralatrexate was approved by the US Food and Drug Administration in 2009 for terminally ill patients, despite its toxicity.
Adverse effects of pralatrexate include fatigue, nausea and mucositis – inflammation and ulceration of the mucous membranes lining the digestive tract.
However, reusing pralatrexate in a way that eliminates its side effects shows a lot of potential, according to the researchers.
Scanning electron micrograph of an apoptotic (pink) cell heavily infected with SARS-COV-2 virus particles (green), isolated from a patient sample. pralatrexate, a chemotherapy drug originally developed to treat lymphoma, could potentially be reused to treat Covid-19
“Identifying effective drugs that can treat Covid-19 is important and urgent, especially approved drugs that can be immediately tested in clinical trials,” say the study authors, led by Dr. Haiping Zhang at the Institutes of Advanced Technology in Shenzhen, China .
“Our study found that pralatrexate is capable of potently inhibiting the replication of SARS-CoV-2 with a stronger inhibitory activity than remedying under the same experimental conditions.
After the global Covid-19 outbreak, researchers were inspired by the idea of reusing existing drugs that were originally developed to treat other diseases.
Remdesivir was initially developed to treat hepatitis C and then reused as a potential treatment for Ebola. Because of the similarity in the structure of these viruses to SARS-CoV-2, the virus that causes Covid-19, experts hope it can help fight the current pandemic.
Artificial intelligence can help identify these drugs, simulating how different drugs would interact with SARS-CoV-2, the virus that causes Covid-19.
To help with the virtual screening of existing drugs, Zhang and colleagues combined several computer techniques that simulate interactions between drugs and viruses.
They used this hybrid approach to screen 1,906 existing drugs for their potential ability to inhibit SARS-CoV-2 replication, targeting a viral protein called RNA-dependent RNA polymerase (RdRP).
RdRP is an essential protein encoded in the genomes of all viruses that contain RNA, such as SARS-CoV-2.
The new screening approach identified four promising drugs, which were tested against SARS-CoV-2 in laboratory experiments.
Two of the drugs, pralatrexate and azithromycin, successfully inhibited virus replication.
Other laboratory experiments showed that pralatrexate inhibited viral replication more strongly than remdesivir, suggesting that the former could potentially be reused for Covid.
However, this chemotherapy drug can cause significant side effects and, as it is used for people with terminal lymphoma, immediate use for patients with Covid-19 is not guaranteed.
Despite this, the results support the use of the new screening strategy to identify drugs that could be adjusted, according to the team.
“We demonstrate the value of our new hybrid approach that combines deep learning technologies with more traditional simulations of molecular dynamics,” said Dr. Zhang.
The researchers, who published their work in PLOS Computational Biology, are now developing additional computational methods to generate new molecular structures that can be developed into new drugs to treat Covid-19.
The study follows some general skepticism about the effectiveness of remdesivir, which was initially developed to treat hepatitis C and then reused as a potential treatment for Ebola.
After disappointing results in treating Ebola in 2014, remdesivir was tested in the early stages of this year’s pandemic.
There is no consensus on whether it is effective, however, with clinical trials showing mixed results.
The NHS approved it for use in patients with Covid-19 in hopes of helping, but they are already being forced to ration the drug, which costs £ 2,400 per treatment ($ 3,120).
In November, the World Health Organization (WHO) said doctors should not treat patients with coronavirus with remdesivir ‘regardless of how sick they were’.
Authorities at the time said “there is no evidence” that it increases people’s chances of surviving the disease or prevents them from getting sick enough to need mechanical ventilation. ”
They also warned that there is a “possibility of major damage” when using the experimental Ebola medicine, 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 treatment with Covid-19 “for some patients”.
It helped cure a 31-year-old patient who suffered a rare reaction to the disease due to a genetic disease called XLA, which prevented him from producing antibodies to fight the infection.
“There have been different studies supporting or questioning the effectiveness of remdesivir, but some of those conducted during the first wave of infection may not be ideal for assessing its antiviral properties,” said study author, Dr. James Thaventhiran, from the MRC Toxicology Unit. from the University of Cambridge.