Dimerized fusion inhibitor peptides targeting the HR1–HR2 interaction of SARS-CoV-2

Tsuji, Kohei; Owusu, Kofi Baffour-Awuah; Ishii, Takahiro; Shinohara, Kouki; Kobayakawa, Takuya; Emi, Akino; Nakano, Takashi; Suzuki, Youichi; Tamamura, Hirokazu

doi:10.1039/d2ra07356k

Cited by 2 publications

(2 citation statements)

References 32 publications

(58 reference statements)

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“…Of note, previously reported fusion inhibitory peptides against SARS-CoV-2 also contain this critical amino acid region (Table S1, ESI†). 28–34…”

Section: Resultsmentioning

confidence: 99%

Helix-based screening with structure prediction using artificial intelligence has potential for the rapid development of peptide inhibitors targeting class I viral fusion

Suzuki,

Kuroda,

Aoki

et al. 2024

RSC Chem. Biol.

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“…Of note, previously reported fusion inhibitory peptides against SARS-CoV-2 also contain this critical amino acid region (Table S1, ESI†). 28–34…”

Section: Resultsmentioning

confidence: 99%

Helix-based screening with structure prediction using artificial intelligence has potential for the rapid development of peptide inhibitors targeting class I viral fusion

Suzuki,

Kuroda,

Aoki

et al. 2024

RSC Chem. Biol.

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“…conservative nature, HR2 peptide derivative fusion inhibitors are an important class of viral therapeutics. Peptides derived from HR2 have demonstrated the ability to bind to the HR1 trimer inner core and exhibit antiviral activity against various coronaviruses 42,43. Among these peptides, the pan-coronavirus fusion inhibitor EK1 or EK1C4 has shown neutralizing activity against a broad spectrum of coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2 variants 44.…”

mentioning

confidence: 99%

Empowering SARS‐CoV‐2 variant neutralization with a bifunctional antibody engineered with tandem heptad repeat 2 peptides

Kim,

Lee,

Kim

et al. 2024

Journal of Medical Virology

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With the global pandemic and the continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the need for effective and broadly neutralizing treatments has become increasingly urgent. This study introduces a novel strategy that targets two aspects simultaneously, using bifunctional antibodies to inhibit both the attachment of SARS‐CoV‐2 to host cell membranes and viral fusion. We developed pioneering IgG4‐(HR2)4 bifunctional antibodies by creating immunoglobulin G4‐based and phage display‐derived human monoclonal antibodies (mAbs) that specifically bind to the SARS‐CoV‐2 receptor‐binding domain, engineered with four heptad repeat 2 (HR2) peptides. Our in vitro experiments demonstrate the superior neutralization efficacy of these engineered antibodies against various SARS‐CoV‐2 variants, ranging from original SARS‐CoV‐2 strain to the recently emerged Omicron variants, as well as SARS‐CoV, outperforming the parental mAb. Notably, intravenous monotherapy with the bifunctional antibody neutralizes a SARS‐CoV‐2 variant in a murine model without causing significant toxicity. In summary, this study unveils the significant potential of HR2 peptide‐driven bifunctional antibodies as a potent and versatile strategy for mitigating SARS‐CoV‐2 infections. This approach offers a promising avenue for rapid development and management in the face of the continuously evolving SARS‐CoV‐2 variants, holding substantial promise for pandemic control.

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Dimerized fusion inhibitor peptides targeting the HR1–HR2 interaction of SARS-CoV-2

Abstract: C-Terminally dimerized HR2 peptides of SARS-CoV-2 showed significantly higher antiviral activity than the corresponding monomers. Our dimerization strategy of HIV-1 fusion inhibitors successfully facilitated the design of potent inhibitors of SARS-CoV-2.

Cited by 2 publications

References 32 publications

Helix-based screening with structure prediction using artificial intelligence has potential for the rapid development of peptide inhibitors targeting class I viral fusion

Helix-based screening with structure prediction using artificial intelligence has potential for the rapid development of peptide inhibitors targeting class I viral fusion

Empowering SARS‐CoV‐2 variant neutralization with a bifunctional antibody engineered with tandem heptad repeat 2 peptides

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