Dimerized Fusion Inhibitor Peptides Targeting the HR1-HR2 Interaction of SARS-CoV-2

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 Mar 23

PMID 36950081

Authors

Kohei Tsuji

Kofi Baffour-Awuah Owusu

Yutaro Miura

Takahiro Ishii

Kouki Shinohara

Takuya Kobayakawa

Akino Emi

Takashi Nakano

Youichi Suzuki

Hirokazu Tamamura

Affiliations

Soon will be listed here.

Abstract

Membrane fusion is a critical and indispensable step in the replication cycles of viruses such as SARS-CoV-2 and human immunodeficiency virus type-1 (HIV-1). In this step, a trimer of the heptad repeat 1 (HR1) region interacts with the three HR2 regions and forms a 6-helix bundle (6-HB) structure to proceed with membrane fusion of the virus envelope and host cells. Recently, several researchers have developed potent peptidic SARS-CoV-2 fusion inhibitors based on the HR2 sequence and including some modifications. We have developed highly potent HIV-1 fusion inhibitors by dimerization of its HR2 peptides. Here, we report the development of dimerized HR2 peptides of SARS-CoV-2, which showed significantly higher antiviral activity than the corresponding monomers, suggesting that the dimerization strategy can facilitate the design of potent inhibitors of SARS-CoV-2.

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