In preclinical models, antiviral better inhibits COVID-19 than Remdesivir; further studies warranted

January 25, 2021

Working in preclinical models, researchers report that plitidepsin, a drug with limited clinical approval for the treatment of multiple myeloma, is more potent against SARS-CoV-2 than remdesivir, an antiviral that received FDA emergency use authorization for the treatment of COVID-19 in 2020. The results suggest plitidepsin should be further evaluated as a COVID-19 therapy, the authors say; because it targets a host protein rather than a viral protein, if treatment proves successful in humans, the SARS-CoV-2 virus won't be easily able to gain resistance against the drug through mutation. The ongoing SARS-CoV-2 pandemic has created the need for antiviral therapeutics that can be swiftly moved into the clinic. This has led researchers to screen clinically approved antivirals. While traditional antivirals, like remdesivir, target viral enzymes that are often subject to mutation, and thus to the development of drug resistance, antivirals that target the cell host proteins required for viral replication could avoid resistance. In earlier work investigating host proteins likely to play a role in the viral life cycle of SARS-CoV-2, including a study in Science in October 2020, Kris White and colleagues found that targeting the host translation machinery that is used in the replication of many viral pathogens could greatly inhibit SARS-CoV-2. Based on this they evaluated plitidepsin, a known inhibitor of a protein involved in host protein translation. In addition to having a limited clinical approval for treating multiple myeloma, it has also successfully completed a phase I/II clinical study for the treatment of COVID-19. Here, in studies in human cells, plitidepsin demonstrated potent anti-SARS-CoV-2 activity - 27.5-fold more so than remdesivir as tested in the same cell line. In a model of human lung cells, plitidepsin greatly reduced viral replication. After further experiments involving remdesivir and plitidepsin in vitro, the researchers suggest that plitidepsin has an additive effect with this approved drug and would be a potential candidate for a combined therapy. The researchers also tested the drug in mice later infected with SARS-CoV-2. Mice who received the drug prophylactically had reduced viral load and lung inflammation compared to control mice. "We believe that our data and the initial positive results from PharmaMar's clinical trial suggests that plitidepsin should be strongly considered for expanded clinical trials for the treatment of COVID-19," conclude the authors.
-end-


American Association for the Advancement of Science

Related Multiple Myeloma Articles from Brightsurf:

Penn Study supports use of radiation before CAR therapy for multiple myeloma
Administering radiation therapy to multiple myeloma patients waiting for CAR T cells to be manufactured was found to be safe and undisruptive to CAR T therapy.

New multiple myeloma therapy shows promise in preclinical study
A new alpha-radioimmunotherapy, 212Pb-anti-CD38, has proven effective in preventing tumor growth and increasing survival in multiple myeloma tumor-bearing mice, according to new research published in the July issue of The Journal of Nuclear Medicine.

A safer cell therapy harnesses patient T cells to fight multiple myeloma
A treatment for multiple myeloma that harnesses the body's cancer-fighting T cells was safe in humans and showed preliminary signs of effectiveness, according to a clinical trial involving 23 patients with relapsed or treatment-resistant disease.

Colorado tool, My-DST, may pick best multiple myeloma treatment
Response of liquid biopsies to approved drugs can help show resistance, predict response.

Case study: Treating COVID-19 in a patient with multiple myeloma
A case study of a patient in Wuhan, China, suggests that the immunosuppressant tocilizumab may be an effective COVID-19 treatment for very ill patients who also have multiple myeloma and other blood cancers.

New drug could reverse treatment resistance in advanced multiple myeloma
Researchers at the VU University Medical Center in the Netherlands have tested a new drug in patient samples and mice with multiple myeloma and discovered that it was effective even in advanced disease -- a point when many patients currently run out of options.

Single gene cluster loss may contribute to initiation/progression of multiple myeloma
The loss of one copy of the miR15a/miR16-1 gene cluster promoted initiation and progression of multiple myeloma in mice.

New CAR-T target yields promising results for multiple myeloma
In research published today in the journal Nature Communications, Utah-based scientists describe a novel way to treat cancers using chimeric antigen receptor (CAR) T cell therapy.

BCMA-targeted immunotherapy can lead to durable responses in multiple myeloma
An experimental, off-the-shelf immunotherapy that combines a targeted antibody and chemotherapy can lead to potentially durable responses in multiple myeloma patients whose disease has relapsed or is resistant to other standard therapies.

Study finds racial disparities in treatment of multiple myeloma patients
Among patients with multiple myeloma, African-Americans and Hispanics start treatment with a novel therapy significantly later than white patients, according to a new study published today in Blood Advances.

Read More: Multiple Myeloma News and Multiple Myeloma Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.