Stapled peptides as potential inhibitors of SARS‐CoV‐2 binding to the hACE2 receptor. (26th February 2022)

• Record Type: Journal Article
• Authors: Tzotzos, Susan
• Is Part Of: Journal of peptide science. Volume 28:Number 9(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-26
• Subjects: COVID‐19 -- hACE2 -- inhibitor -- peptide -- SARS‐CoV‐2 -- stapling -- therapeutic; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3409
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Stapled peptides are synthetic peptidomimetics of bioactive sites in folded proteins which carry chemical links, introduced during peptide synthesis, designed to retain the secondary structure in the native protein molecule. Stapled peptides have been investigated as potential modulators of protein–protein interactions for over two decades. The potential use of stapled peptides as inhibitors of viral entry, and therefore as antiviral therapeutics, has been established for several important viruses causing disease in humans, such as the human immunodeficiency virus type 1 (HIV‐1), respiratory syncytial virus (RSV), and Middle East Respiratory Syndrome (MERS) coronavirus. Several independent research initiatives have investigated the inhibitory effect of stapled peptides on binding of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative agent of COVID‐19, to its receptor, angiotensin‐converting‐enzyme 2 (ACE2). These stapled peptides, which mimic Helix 1 of the human ACE2 receptor, have demonstrated mixed ability to prevent infection with SARS‐CoV‐2 in cell‐based studies. Abstract : Peptides mimicking a helical region of the hACE2 receptor (Helix 1), to which SARS‐CoV‐2 initially binds in the host cell membrane, could potentially be developed as COVID‐19 therapeutics. Peptidomimetics of Helix 1, whose secondary structure has been stabilized by hydrocarbon and lactam bridge stapling, have been tested in vitro for their antiviral activity by several research groups, with mixed results.