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Aplidine (Plitidepsin) is a potent anti-cancer agent by targeting eEF1A2 ( K_D=80 nM). Aplidine possesses antiviral activity and is against SARS-CoV-2 with an IC₉₀ of 0.88 nM. Aplidine is usually used for multiple myeloma and advanced cancer research, and has the potential for COVID-19 research.

Aplidine (20 nM; 1 h) induces a dose-dependent decrease in VEGF secretion in MOLT-4 cells.
Aplidine (20 nM; 1 h) does not result in significant inhibition of VEGF-R1 mRNA in normal endothelial cells, which do express VEGFR-1 but do not secrete VEGF.
Aplidine inhibits SARS-CoV-2 with an IC₉₀ of 1.76 nM. In hACE2-293T cells, Aplidine exhibits anti–SARS-CoV-2 activity with an IC₉₀ of 0.88 nM. In an established model of human pneumocyte-like cells, Aplidine inhibits SARS-CoV-2 replication with an IC₉₀ of 3.14 nM and a selectivity index of 40.4.

Plitidepsin (intraperitoneal injection; 0.3 mg/kg or 1 mg/kg; 2 hours before infection with SARS-CoV-2) significantly reduces SARS-CoV-2 infection in BALB/c mice expressing human ACE2. 0.3 mg/kg plitidepsin group results in a reduction of nearly 2 log units in SARS-CoV-2 viral titers in the lungs, and the 1 mg/kg group leads to a reduction of 1.5 log units relative to the vehicle control group.

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