[ad_1]
Research among existing drugs of potential COVID-19 treatments has highlighted another promising candidate – an anti-cancer drug that appears to perform better than Gilead Sciences’ FDA-approved remdesivir against the SARS-CoV-2 virus in l origin of the disease.
In a new study published in Science, researchers at the Icahn School of Medicine at Mount Sinai and the University of California at San Francisco found in preclinical experiments that plitidepsin from Spanish drug maker PharmaMar, approved as Aplidin brand in some countries for multiple myeloma, was almost 30 times more potent than remdesivir.
Additionally, in a separate article published on the journal bioRxiv’s preprint site, the researchers showed that the drug had comparable antiviral activity against the original strain of SARS-CoV-2 and the more contagious new B117 variant, first discovered in the UK.
Based on the positive results, PharmaMar said it was in talks with regulatory agencies to initiate Phase 3 clinical trials of plitidepsin in COVID.
RELATED: PTC Therapeutics Operates Investigational Cancer Drug for New COVID-19 Trial
Plitidepsin was derived from Aplidium albicans, a sea spray found off the coast of Spain. It was originally intended to target the human protein eEF1A, the expression of which can lead to cell signaling leading to cancer.
The team led by Icahn had previously found that targeting certain host proteins involved in the gene-to-protein translation machinery – which is essential for the replication of many viral pathogens – can block SARS-CoV-2. This discovery led them to test plitidepsin.
In the new study, scientists confirmed that plitidepsin does work against SARS-CoV-2 by inhibiting eEF1A, which interacts with the coronavirus core (N) protein during infection.
In studies on human cells, plitidepsin demonstrated anti-SARS-CoV-2 activity that was 27.5 times more potent than that of remdesivir. As remdesivir was cleared by the FDA to treat COVID-19, the researchers tested plitidepsin alongside the drug Gilead. Their analysis suggests that plitidepsin has an “additive effect” on remdesivir.
The researchers also tested the drug in two different mouse models. In mice that received plitidepsin shortly before being infected with SARS-CoV-2, the drug significantly reduced viral load and lung inflammation compared to controls. Plitidepsin caused a reduction in viral load comparable to that of remdesivir, but the anticancer drug was more effective in relieving inflammation in the lungs, the team reported.
Plitidepsin holds a potential advantage over traditional antivirals like remdesivir, the team argued. By targeting the host protein rather than viral proteins, plitidepsin could potentially avoid drug resistance that can result from mutations.
In the second study, the team tested plitidepsin against the more highly transmissible B117 variant of SARS-CoV-2. The drug showed similar antiviral activity against both the early lineage virus and the mutated version in human gastrointestinal and lung epithelial cell lines, and it was significantly more potent than remdesivir against both viruses, found the team.
Reusing existing drugs is a popular strategy among scientists looking for possible treatments for COVID-19. Several other anticancer drugs have been proposed to either directly inhibit the virus or to attenuate the unwanted inflammatory response resulting from infection with SARS-CoV-2.
PTC Therapeutics is testing its DHODH inhibitor PTC299 in a phase 2/3 trial based on the belief that the drug can both inhibit viral replication and suppress the production of inflammatory molecules. AstraZeneca previously evaluated its treatment for BTK Calquence blood cancer in COVID-19, but the drug has failed to reduce rates of death or respiratory failure.
PharmaMar already has phase 1/2 positive data for plitidepsin in COVID-19. In October, the company said that the APLICOV-PC (PDF) trial showed that plitidepsin resulted in a significant reduction in viral load in hospitalized patients and that a remarkable correlation was observed between the reduction in the load viral and clinical improvement, among other measures.
“We believe our data and the first positive results from the PharmaMar clinical trial suggest that plitidepsin should be strongly considered for expanded clinical trials for the treatment of COVID-19,” the Mount Sinai-UCSF team wrote in the Science study.
Source link
