A drug 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 drug that was originally developed to treat lymphomas, tumors that originate in the glands.
Chinese researchers found that pralatrexate surpasses remdesivir, which is currently the main antiviral drug used to treat patients with covid-19.
Prostatexate was approved by the U.S. 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, according to the researchers, reusing pralatrexate in a way that eliminates its side effects shows great potential.
Color scanning electron micrograph of an apoptotic cell (pink) heavily infected with SARS-VOC-2 virus particles (green), isolated from a patient sample. pralatrexate, a chemotherapy drug originally developed to treat lymphoma, could be reused to treat Covid-19
“Identifying effective drugs that can treat Covid-19 is important and urgent, especially approved drugs that can be tested immediately in clinical trials,” say the study’s authors, led by Drs. Haiping Zhang of the Institute of Advanced Technology of Shenzhen, China.
“Our study found that pralatrexate is capable of potently inhibiting SARS-CoV-2 replication with stronger inhibitory activity than remdesivating under the same experimental conditions.”
Following the global outbreak of Covid-19, researchers were inspired by the idea of reusing existing drugs that were originally developed to treat other conditions.
Remdesivir was initially developed to treat hepatitis C and was later reused as a potential treatment for Ebola, due to the similarity in the structures of these viruses to SARS-CoV-2, the virus that causes hepatitis C. Covid-19, experts hoped it could help fight the current pandemic
Artificial intelligence can help identify these drugs by simulating how different drugs would interact with SARS-CoV-2, the virus that causes Covid-19.
To help virtual screening of existing drugs, Zhang and colleagues combined multiple computational techniques that simulate drug-virus interactions.
They used this hybrid approach to analyze 1,906 existing drugs for their potential ability to inhibit SARS-CoV-2 replication 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 new screening approach identified four promising drugs, which were then 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 be reused for Covid.
However, this chemotherapy drug can cause significant side effects and, as it is used in people with terminal lymphoma, immediate use is not guaranteed for patients with Covid-19.
Despite this, the findings support the use of the new detection strategy to identify drugs that can be modified, according to the team.
“We have demonstrated the value of our new hybrid approach that combines deep learning technologies with more traditional molecular dynamics simulations,” Dr. Zhang said.
Researchers, who have published their work in PLOS Computational Biology, are now developing additional computational methods to generate new molecular structures that could 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 was reused as a potential treatment for Ebola.
After disappointing results on Ebola treatment in 2014, remdesivir was tested in the early stages of this year’s pandemic.
However, there is no consensus on whether it is effective, with clinical trials showing mixed results.
The NHS has approved it for use in Covid-19 patients in hopes that it can help, but it is already being forced to ration the drug, which costs £ 2,400 per course ($ 3,120).
In November, the World Health Organization (WHO) said doctors should not treat coronavirus patients with remdesivir “regardless of the disease they have.”
Officials at the time said there was no “evidence” that would increase the chances of surviving the disease or prevent them from getting sick enough to need mechanical ventilation. ”
They also warned that there is a “possibility of significant harm” when using the experimental drug against Ebola, as it can cause kidney and liver damage in some patients.
However, in December, a team of British experts told Nature Communications that remdesivir could be a highly effective Covid-19 treatment “for some patients”.
He 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 the infection.
“There have been several studies that support or question the effectiveness of remdesivir, but some of those performed during the first wave of infection may not be optimal for evaluating its antiviral properties,” said the author of the study. ‘study, Dr. James Thaventhiran, of the MRC Toxicology Unit at Cambridge University. .