Abstract
The prolonged duration of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has resulted in the continuous emergence of variants of concern (VOC, e.g., Omicron) and variants of interest (VOI, e.g., Lambda). These variants have challenged the protective efficacy of current COVID-19 vaccines, thus calling for the development of novel therapeutics against SARS-CoV-2 and its VOCs. Here, we constructed a novel fusion inhibitor-based recombinant protein, denoted as 5-Helix, consisting of three heptad repeat 1 (HR1) and two heptad repeat 2 (HR2) fragments. The 5-Helix interacted with the HR2 domain of the viral S2 subunit, the most conserved region in spike (S) protein, to block homologous six-helix bundle (6-HB) formation between viral HR1 and HR2 domains and, hence, viral S-mediated cell-cell fusion. The 5-Helix potently inhibited infection by pseudotyped SARS-CoV-2 and its VOCs, including Delta and Omicron variants. The 5-Helix also inhibited infection by authentic SARS-CoV-2 wild-type (nCoV-SH01) strain and its Delta variant. Collectively, our findings suggest that 5-Helix can be further developed as either a therapeutic or prophylactic to treat and prevent infection by SARS-CoV-2 and its variants.
Keywords: 5-Helix; SARS-CoV-2; fusion inhibitor; heptad repeat 1; heptad repeat 2; six-helix bundle; variant of concern.
【저자키워드】 SARS-CoV-2, Variant of concern., fusion inhibitor, 5-Helix, heptad repeat 1, heptad repeat 2, six-helix bundle, 【초록키워드】 Efficacy, pandemic, VoC, variant, Infection, variants of concern, Delta, severe acute respiratory syndrome coronavirus-2, Prophylactic, severe acute respiratory syndrome Coronavirus, omicron, delta variant, Omicron variants, variants, Protein, COVID-19 vaccines, therapeutic, VOCs, variants of interest, cell-cell fusion, homologous, S2 subunit, Protective, Lambda, Coronavirus-2, Recombinant protein, conserved region, acute respiratory syndrome, acute respiratory syndrome coronavirus, domain, acute respiratory syndrome coronavirus-2, treat, nCoV, wild-type, S-mediated cell-cell fusion, pseudotyped SARS-CoV-2, heptad repeat, helix, Prevent, conserved, inhibited, 【제목키워드】 concern, fusion, Repeat, targeting,