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Structure and Function of the SARS-CoV-2 6-HB Fusion Core and Peptide-Based Fusion Inhibitors: A Review


Guodong Liang, Yue Li, Ruijuan Li, Yuheng Ma* and Heiya Na   Pages 1 - 24 ( 24 )


SARS-CoV-2 has swept the world in recent years, triggering a global COVID-19 with a tremendous impact on human health and public safety. Similar to other coronaviruses, the six-helix bundle(6-HB) is not only a core structure driving the fusion of the SARS-CoV-2 envelope with the host cell membrane, but also the target of fusion inhibitors. The sequences from the HR1 or HR2 regions composing 6-HB are thus the original primary structures for the development of peptide-based fusion inhibitors. This review summarized the structure-activity relationship of the SARS-CoV-2 6- HB, analyzed the design methods and functional characteristics of peptide-based fusion inhibitors that contain different regions of HRs, and provided an outlook on the cutting- edge approaches for optimal modification of lead compounds (pan-coronavirization, chemical modification, superhelical construction, etc). We hope that this review will provide researchers with a comprehensive understanding of the state-of-art research progress on both 6-HB and peptide-based fusion inhibitors of SARS-CoV-2, and provide some new insights for the development of antiviral drugs.


SARS-CoV-2, six-helix bundle, Fusion Inhibitors, Peptide.


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