Plitidepsin

Plitidepsin (Aplidine) is a potent anti-cancer agent by targeting eEF1A2 ( K_D=80 nM)^[1]. Plitidepsin possesses antiviral activity and is against SARS-CoV-2 with an IC₉₀ of 0.88 nM. Plitidepsin is usually used for multiple myeloma and advanced cancer research, and has the potential for COVID-19 research^[1][2]. In Vitro: Plitidepsin (20 nM; 1 h) induces a dose-dependent decrease in VEGF secretion in MOLT-4 cells^[1].
Plitidepsin (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^[1].
Plitidepsin inhibits SARS-CoV-2 with an IC₉₀ of 1.76 nM. In hACE2-293T cells, Plitidepsin exhibits anti-SARS-CoV-2 activity with an IC₉₀ of 0.88 nM. In an established model of human pneumocyte-like cells, Plitidepsin inhibits SARS-CoV-2 replication with an IC₉₀ of 3.14 nM and a selectivity index of 40.4^[1].
In Vivo: 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^[2].