General Information

General Information

DRAVP ID DRAVPe01779

Peptide Name Plitidepsin, Aplidine

Sequence PxTXXLPX

Sequence Length 8

UniProt ID No entry found

Source Synthetic construct

Activity Information

Target Organism SARS-CoV-2

Assay antiviral assay

Activity

[Ref.33495306]SARS-CoV-2:inhibition of replication In Vero E6 cells(IC50=0.70 nM,IC90=1.76 nM);inhibition of replication In hACE2-HEK293T cells(IC50=0.73 nM,IC90=0.88 nM);inhibition of replication In pneumocyte-like cells(IC50=1.62 nM,IC90=3.14 nM).
[Ref.35231500]SARS-CoV-2 D614G:inhibition of replication in Vero E6 cells(IC50=5.2 nM);
SARS-CoV-2 Delta:inhibition of replication in Vero E6 cells(IC50=3.9 nM);
SARS-CoV-2 Omicron:inhibition of replication in Vero E6 cells(IC50=4.3 nM).

Hemolytic Activity No hemolysis information or data found in the reference(s) presented in this entry

Cytotoxicity

[Ref.33495306]Vero E6 cells:CC10=0.36 nM,CC50=1.99 nM;hACE2-293T cells:CC10=2.00 nM,CC50>200 nM;pneumocyte-like cells:CC10=20.88 nM,CC50=65.43 nM.

Binding Target Not found

Mechanism The antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A (eukaryotic translation elongation factor 1A).

Structure Information

PDB ID None

Predicted Structure Download No predicted structure available

Linear/Cyclic Linear

N-terminal Modification Pyruvoyl

C-terminal Modification Free

Other Modification The 'X' at position 2 is N-methylleucine,position 4 is 4-amino-3-hydroxy-5-methyl-Heptanoic acid, position 5 is Hydroxyisovalerylpropionyl, and position 8 is N-methyl-4-methyl-tyrosine.There is a Sidechain-Mainchain Bond between position 3 and 8.

Stereochemistry Mixed(D-meth-Leu2)

Physicochemical Information

Formula C20H26N4O2

Absent amino acids ACDEFGHIKMNQRSVWY

Common amino acids X

Mass 871.84

Pl 5.96

Basic residues 0

Acidic residues 0

Hydrophobic residues 1

Net charge 0

Boman Index 235

Hydrophobicity -1.25

Aliphatic Index 48.75

Half Life

Mammalian:>20 hour
Yeast:>20 hour
E.coli:?

Extinction Coefficient cystines 0

Absorbance 280nm 0

Polar residues 1

Literature Information

Literature 1

Title Unraveling the antiviral activity of plitidepsin against SARS-CoV-2 by subcellular and morphological analysis.

Pubmed ID 35231500

Reference Antiviral Res. 2022 Apr;200:105270.

Author Sachse M, Tenorio R, Fernández de Castro I, Muñoz-Basagoiti J, Perez-Zsolt D, Raïch-Regué D, Rodon J, Losada A, Avilés P, Cuevas C, Paredes R, Segalés J, Clotet B, Vergara-Alert J, Izquierdo-Useros N, Risco C.

DOI 10.1016/j.antiviral.2022.105270

Literature 2

Title Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A.

Pubmed ID 33495306

Reference Science. 2021 Feb 26;371(6532):926-931.

Author White KM, Rosales R, Yildiz S, Kehrer T, Miorin L, Moreno E, Jangra S, Uccellini MB, Rathnasinghe R, Coughlan L, Martinez-Romero C, Batra J, Rojc A, Bouhaddou M, Fabius JM, Obernier K, Dejosez M, Guillén MJ, Losada A, Avilés P, Schotsaert M, Zwaka T, Vignuzzi M, Shokat KM, Krogan NJ, Garc

DOI 10.1126/science.abf4058