Repurposed multiple myeloma cancer drug from a sea squirt kills WuFlu virus in mice AND HUMANS 30 times better than remdesivir

https://www.sfchronicle.com/health/article/Cancer-drug-Aplidin-shows-promise-as-COVID-15896461.php

‘New weapon’ to kill COVID? UCSF-led team finds drug that could be far more effective than remdesivir

Jason Fagone Jan. 25, 2021 Updated: Jan. 25, 2021 3:06 p.m.

After a yearlong search for existing drugs that might help COVID-19 patients and point to a cure, a UCSF-led science team has identified what they say is an especially promising candidate: an anti-cancer drug that kills the coronavirus in lab studies and is almost 30 times more potent than remdesivir, one of the few antiviral drugs available to treat the disease.

The new peer-reviewed research, published Monday in the journal Science, highlights a drug called Aplidin, which was originally extracted from an exotic marine creature called Aplidium albicans — a type of “sea squirt” found off the coast of Ibiza that looks a bit like a disembodied brain.

Aplidin, also known as plitidepsin, is owned by Pharma Mar, a Spanish company founded by a scuba-diving scientist. Already approved in Australia to treat multiple myeloma, a type of blood cancer, the drug isn’t commercially available in most parts of the world and isn’t yet approved to treat COVID-19, though it has been tested in a few dozen COVID-19 patients in Spain.

[Moar at website]

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Journal article:

https://science.sciencemag.org/content/early/2021/01/22/science.abf4058

Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1Ax

Kris M. White, Romel Rosales, Soner Yildiz, Thomas Kehrer, Lisa Miorin, Elena Moreno, et al

Science 25 Jan 2021:

eabf4058

DOI: 10.1126/science.abf4058

Abstract

SARS-CoV-2 viral proteins interact with the eukaryotic translation machinery and inhibitors of translation have potent antiviral effects. Here we report that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (IC90 = 0.88 nM) 27.5-fold more potent than remdesivir against SARS-CoV-2 in vitro, with limited toxicity in cell culture. Through the use of a drug resistant mutant, we show that the antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A. We demonstrate the in vivo efficacy of plitidepsin treatment in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment. Our results indicate that plitidepsin is a promising therapeutic candidate for COVID-19.

[Moar at website]