Perplexing and unusual as it seems, the sea quirt’s rare extract, known as plitidepsin, was discovered years ago by Spanish drugmaker PharmaMar and was marketed, under the name Aplidin, as a treatment for a rare type of cancer. The compound is promising as a COVID-19 antiviral drug as it inhibits human protein eEF1A and prevents viral replication thereby suppressing SARS-COV-2.
What makes plitidepsin so intriguing in the fight against COVID-19? The answer is twofold. Firstly, according to new studies in human cells reported in Science, plitidepsin is almost 30 times more potent than remdesivir, the first antiviral drug licensed for the treatment COVID-19 patients.
Secondly, and perhaps even more provoking, the researchers took a novel approach to identifying proteins, which could prove critical in the fight against COVID-19, drug resistance, and mutations.
Rather than taking the common path of identifying drugs that target viral proteins, Nevan Krogan, University of California, and Kris M. White and Adolfo García-Sastre, Icahn School of Medicine at Mount Sinai, have instead investigated the role that host proteins play in the viral life cycle and identified compounds that demonstrate strong antiviral activity.
By targeting human proteins like eEf1A rather than viral proteins, plitidepsin has the potential to address the common issues associated with drug efficacy against viral mutations given that host proteins do not mutate as quickly as viral proteins. Consequently, these efforts targeting the human protein with plitidepsin have the potential to retain efficacy in spite of viral mutations.
There remain questions surrounding targeting a host protein and its problems related to toxicity, a critical concern for cancer patients being treated with plitidepsin. However, researchers note that the dosage required to kill SARS-CoV-2 is incomparable in terms of amount and length of treatment.
With encouraging Phase 2 clinical trial results from the APLICOV-PC study, PharmaMar is currently discussing the initiation of phase 3 clinical trials of plitidepsin to treat COVID-19 with regulatory agencies.