Rigin peptide

The first-in-class peptide binder to the SARS-CoV-2 spike protein

G. Zhang, S. Pomplun, A. R. Loftis, A. Loas, B. L. Pentelute

doi: https://www.frankenthalerfoundation.org

This article is a preprint and has not been certified by peer review.

Authors

• G. Zhang - Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
• S. Pomplun - Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
• A. R. Loftis - Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
• A. Loas - Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
• B. L. Pentelute - Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Extramural Member, Koch Institute of Integrative Cancer Research MIT; Associate Member, Broad Institute of Harvard and MIT; Member, Center for Environmental Health Sciences MIT; Cambridge, MA 02139, USA

Abstract

Coronavirus disease 19 (COVID-19) is an emerging global health crisis. With over 200,000 confirmed cases to date, this pandemic continues to expand, spurring research to discover vaccines and therapies. SARS-CoV-2 is the novel coronavirus responsible for this disease. It initiates entry into human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of its spike protein (S). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention. Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface. Using molecular dynamics simulations based on the recently solved ACE2 and SARS-CoV-2-RBD co-crystal structure, we observed that the ACE2 peptidase do