Your browser doesn't support javascript.
Targeting the Receptor-Binding Motif of SARS-CoV-2 with D-Peptides Mimicking the ACE2 Binding Helix: Lessons for Inhibiting Omicron and Future Variants of Concern.
Valiente, Pedro A; Nim, Satra; Lee, JinAh; Kim, Seungtaek; Kim, Philip M.
  • Valiente PA; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Nim S; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Lee J; Zoonotic Virus Laboratory, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
  • Kim S; Zoonotic Virus Laboratory, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
  • Kim PM; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
J Chem Inf Model ; 62(15): 3618-3626, 2022 08 08.
Article in English | MEDLINE | ID: covidwho-1960220
ABSTRACT
The COVID-19 pandemic continues to spread around the world, with several new variants emerging, particularly those of concern (VOCs). Omicron (B.1.1.529), a recent VOC with many mutations in the spike protein's receptor-binding domain (RBD), has attracted a great deal of scientific and public interest. We previously developed two D-peptide inhibitors for the infection of the original SARS-CoV-2 and its VOCs, alpha and beta, in vitro. Here, we demonstrated that Covid3 and Covid_extended_1 maintained their high-affinity binding (29.4-31.3 nM) to the omicron RBD. Both D-peptides blocked the omicron variant in vitro infection with IC50s of 3.13 and 5.56 µM, respectively. We predicted that Covid3 shares a larger overlapping binding region with the ACE2 binding motif than different classes of neutralizing monoclonal antibodies. We envisioned the design of D-peptide inhibitors targeting the receptor-binding motif as the most promising approach for inhibiting current and future VOCs of SARS-CoV-2, given that the ACE2 binding interface is more limited to tolerate mutations than most of the RBD's surface.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: J Chem Inf Model Journal subject: Medical Informatics / Chemistry Year: 2022 Document Type: Article Affiliation country: Acs.jcim.2c00500

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: J Chem Inf Model Journal subject: Medical Informatics / Chemistry Year: 2022 Document Type: Article Affiliation country: Acs.jcim.2c00500