Targeting SARS-CoV-2 Receptor Binding Domain with Stapled Peptides: AnIn SilicoStudy

Luana Janaína de Campos, Nicholas Y. Palermo, Martin Conda-Sheridan

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a pandemic of unprecedented scale. This coronavirus enters cells by the interaction of the receptor binding domain (RBD) with the human angiotensin-converting enzyme 2 receptor (hACE2). In this study, we employed a rational structure-based design to propose 22-mer stapled peptides using the structure of the hACE2 α1 helix as a template. These peptides were designed to retain the α-helical character of the natural structure, to enhance binding affinity, and to display a better solubility profile compared to other designed peptides available in the literature. We employed different docking strategies (PATCHDOCK and ZDOCK) followed by a double-step refinement process (FIBERDOCK) to rank our peptides, followed by stability analysis/evaluation of the interaction profile of the best docking predictions using a 500 ns molecular dynamics (MD) simulation, and a further binding affinity analysis by molecular mechanics with generalized Born and surface area (MM/GBSA) method. Our most promising stapled peptides presented a stable profile and could retain important interactions with the RBD in the presence of the E484K RBD mutation. We predict that these peptides can bind to the viral RBD with similar potency to the control NYBSP-4 (a 30-mer experimentally proven peptide inhibitor). Furthermore, our study provides valuable information for the rational design of double-stapled peptide as inhibitors of SARS-CoV-2 infection.

Original languageEnglish (US)
Pages (from-to)6572-6586
Number of pages15
JournalJournal of Physical Chemistry B
Issue number24
StatePublished - Jun 24 2021

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


Dive into the research topics of 'Targeting SARS-CoV-2 Receptor Binding Domain with Stapled Peptides: AnIn SilicoStudy'. Together they form a unique fingerprint.

Cite this