DRAVP ID  DRAVPs019

Peptide Name   NYBSP-4

Sequence  TIEEQⓏKTFLDKⓍNHEAEDLFYQⓍSLAⓍWN

Sequence Length  30

Original Sequence  TIEEQKTFLDKNHEAEDLFYQSLAWN

Source  Synthetic Construct

Validation   Experimentally Validated

Target Organism  SARS-CoV-2

Assay  Inhibition assay

Activity 

• [Ref.33310780]Virus:
• SARS-CoV-2:Inhibition of infection in HT1080/ACE2 cells(IC50=1.97 ± 0.14 μM);Inhibition of infection in A549/ACE2 cells(IC50=2.8 ± 0.08 μM);Inhibition of virus-induced cytopathic effect (CPE) in Vero E6 cells(IC100=33 μM);
• VSV-G:Inhibition of infection in HT1080/ACE2 cells(IC50>26.6 μM);Inhibition of infection in A549/ACE2 cells(IC50>26.6 μM).

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

Cytotoxicity 

• [Ref.33310780]HT1080/ACE2 cells:CC50>26.6 μM(Less than 10% toxicity at this dose);A549/ACE2 cells:CC50>26.6 μM(Less than 10% toxicity at this dose).

Binding Target  membrane

Mechanism  Proteolytic stability of NYBSP-4 in human plasma(half-life (T1/2) of NYBSP-4 was >289 min).The stapled peptide designed based on the ACE2 helix, which is expected to bind to SARS-CoV-2 and prevent the binding of the virus to the ACE2 receptor and disrupt the infection.

Linear/Cyclic  Cyclic

N-terminal Modification  Acetylation

C-terminal Modification  Amidation

Special Amino Acid and Stapling Position  ①The Ⓧ (position: 13,24 and 28) in sequence indicate S-2-(4'-pentenyl) alanine.②The Ⓩ (position: 6) indicates 2-(7'-octenyl) alanine in the R configuration.③ Ⓩ(6) and Ⓧ(13), Ⓧ(24) and Ⓧ(28) are cross-linked by hydrocarbon stapling.

Structure Description  80% α-helical content in 10 mM phosphate-buffered saline (PBS)

Stereochemistry  L

Literature 1

Title   Stapled Peptides Based on Human Angiotensin-Converting Enzyme 2 (ACE2) Potently Inhibit SARS-CoV-2 Infection In Vitro.

Pubmed ID   33310780

Reference   mBio. 2020 Dec 11;11(6):e02451-20.

Author   Curreli F, Victor SMB, Ahmed S, Drelich A, Tong X, Tseng CK, Hillyer CD, Debnath AK.

DOI   10.1002/psc.3409