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Discovery of Small Anti‐ACE2 Peptides to Inhibit SARS‐CoV‐2 Infectivity
Author(s) -
Adhikary Pratik,
Kandel Sashi,
Mamani UmarFarouk,
Mustafa Bahaa,
Hao Siyuan,
Qiu Jianming,
Fetse John,
Liu Yanli,
Ibrahim Nurudeen Mohammed,
Li Yongren,
Lin ChienYu,
Omoscharka Evanthia,
Cheng Kun
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202100087
Subject(s) - vero cell , infectivity , peptide , virology , coronavirus , biopanning , cytotoxicity , covid-19 , angiotensin converting enzyme 2 , biology , virus , hek 293 cells , chemistry , peptide library , receptor , in vitro , peptide sequence , biochemistry , medicine , gene , infectious disease (medical specialty) , pathology , disease
COVID‐19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which infects host cells by binding its viral spike protein receptor‐binding domain (RBD) to the angiotensin converting enzyme 2 (ACE2) on host cells. Blocking the SARS‐CoV‐2‐RBD/ACE2 interaction is, therefore, a potential strategy to inhibit viral infections. Using a novel biopanning strategy, a small anti‐ACE2 peptide is discovered, which shows high affinity and specificity to human ACE2. It blocks not only the SARS‐CoV‐2‐RBD/ACE2 interaction but also the SARS‐CoV‐1‐RBD/ACE2 interaction. Moreover, it inhibits SARS‐CoV‐2 infection in Vero‐E6 cells. The peptide shows negligible cytotoxicity in Vero‐E6 cells and Huh7 cells. In vivo short‐term lung toxicity study also demonstrates a good safety of the peptide after intratracheal administration. The anti‐ACE2 peptide can be potentially used as a prophylactic or therapeutic agent for SARS‐CoV‐2 or other ACE2‐mediated viruses. The strategy used in this study also provides a fast‐track platform to discover other antiviral peptides, which will prepare the world for future pandemics.