A drug that has been used to treat cancer for over a decade could 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 found that pralatrexate outperforms remdesivir, which is currently the main antiviral medication used to treat Covid-19 patients.
Pralatrexate was approved by the U.S. Food and Drug Administration in 2009 for patients with terminal illness, despite its toxicity.
Side effects of pralatrexate include fatigue, nausea, and mucositis – inflammation and ulceration of the mucous membranes lining the digestive tract.
However, according to researchers, it shows a lot of potential to repurpose pralatrexate in a way that eliminates its side effects.
Stained scanning electron microscope of an apoptotic cell (pink) 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 those approved drugs that can be immediately tested in clinical trials, ” say the study authors, led by Dr. Haiping Zhang of the Shenzhen Institutes of Advanced Technology, China.
‘Our study found that pralatrexate is able to potently inhibit SARS-CoV-2 replication with stronger inhibitory activity than remdesivir within the same experimental conditions.
After the global outbreak of Covid-19, researchers were inspired by the idea of reusing existing drugs originally developed to treat other conditions.
Remdesivir was initially developed to treat hepatitis C and was then reused as a potential Ebola treatment. Due to the similarity in the structures of these viruses to SARS-CoV-2, the virus that causes Covid-19, experts hoped it could help combat it. of the current pandemic
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 support virtual screening of existing drugs, Zhang and colleagues have 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 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 the replication of the virus.
Further 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, since it is used for those 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 can be modified, the team said.
“We have demonstrated 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 have published their work in PLOS Computational Biology, are now developing additional computational methods for generating new molecular structures that can be developed into new drugs to treat Covid-19.
The study follows some general skepticism regarding the efficiency of remdesivir, which was initially developed to treat hepatitis C and then reused as a potential Ebola treatment.
After disappointing results in the treatment of Ebola in 2014, Remdesivir was tested in the early stages of this year’s pandemic.
However, there is no consensus as to whether it is effective as clinical studies show mixed results.
The NHS has approved it for use in Covid-19 patients in the hope it can help, but 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 “no matter how sick they are.”
Officials at the time said there is “no evidence” that it increases people’s chances of surviving the disease or keeps them from getting sick enough to need mechanical ventilation. ”
They also warned that there is a “potential for significant harm” with the use of the experimental Ebola drug, as it can cause kidney and liver damage in some patients.
In December, a team of British experts in Nature Communications reported that remdesivir could be a very effective Covid-19 treatment “for some patients.”
It had helped cure a 31-year-old patient who suffered a rare disease reaction due to a genetic condition called XLA that prevented him from making antibodies to fight infections.
“ There have been several studies that support or question the effectiveness of remdesivir, but some of the studies conducted during the initial wave of infection may not be optimal for assessing its antiviral properties, ” said study author Dr. James Thaventhiran from the MRC Toxicology Unit at Cambridge University. .