Heptad Repeat-derived Peptides Block Protease-mediated Direct Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus but Not Entry Via the Endosomal Pathway

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2007 Oct 19

PMID 17942557

Citations 34

Authors

Makoto Ujike

Hiroki Nishikawa

Akira Otaka

Naoki Yamamoto

Norio Yamamoto

Masao Matsuoka

Eiichi Kodama

Nobutaka Fujii

Fumihiro Taguchi

Affiliations

Soon will be listed here.

Abstract

The peptides derived from the heptad repeat (HRP) of severe acute respiratory syndrome coronavirus (SCoV) spike protein (sHRPs) are known to inhibit SCoV infection, yet their efficacies are fairly low. Recently our research showed that some proteases facilitated SCoV's direct entry from the cell surface, resulting in a more efficient infection than the previously known infection via endosomal entry. To compare the inhibitory effect of the sHRP in each pathway, we selected two sHRPs, which showed a strong inhibitory effect on the interaction of two heptad repeats in a rapid and virus-free in vitro assay system. We found that they efficiently inhibited SCoV infection of the protease-mediated cell surface pathway but had little effect on the endosomal pathway. This finding suggests that sHRPs may effectively prevent infection in the lungs, where SCoV infection could be enhanced by proteases produced in this organ. This is the first observation that HRP exhibits different effects on virus that takes the endosomal pathway and virus that enters directly from the cell surface.

Citing Articles

Biochemical analysis of packing and assembling heptad repeat motifs in the coronavirus spike protein trimer.

Kobayashi J, Kanou K, Okura H, Akter T, Fukushi S, Matsuyama S mBio. 2024; 15(11):e0120324.

PMID: 39440974 PMC: 11559096. DOI: 10.1128/mbio.01203-24.

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

Suzuki S, Kuroda M, Aoki K, Kawaji K, Hiramatsu Y, Sasano M RSC Chem Biol. 2024; 5(2):131-140.

PMID: 38333196 PMC: 10849125. DOI: 10.1039/d3cb00166k.

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

Tsuji K, Baffour-Awuah Owusu K, Miura Y, Ishii T, Shinohara K, Kobayakawa T RSC Adv. 2023; 13(13):8779-8793.

PMID: 36950081 PMC: 10026625. DOI: 10.1039/d2ra07356k.

Design and characterization of novel SARS-CoV-2 fusion inhibitors with N-terminally extended HR2 peptides.

Hu Y, Zhu Y, Yu Y, Liu N, Ju X, Ding Q Antiviral Res. 2023; 212:105571.

PMID: 36868315 PMC: 9977133. DOI: 10.1016/j.antiviral.2023.105571.

Peptide-based inhibitors hold great promise as the broad-spectrum agents against coronavirus.

Tang M, Zhang X, Huang Y, Cheng W, Qu J, Gui S Front Microbiol. 2023; 13:1093646.

PMID: 36741878 PMC: 9893414. DOI: 10.3389/fmicb.2022.1093646.

References

Yang Z, Huang Y, Ganesh L, Leung K, Kong W, Schwartz O . pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J Virol. 2004; 78(11):5642-50. PMC: 415834. DOI: 10.1128/JVI.78.11.5642-5650.2004. View

Inoue Y, Tanaka N, Tanaka Y, Inoue S, Morita K, Zhuang M . Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ACE2 with the cytoplasmic tail deleted. J Virol. 2007; 81(16):8722-9. PMC: 1951348. DOI: 10.1128/JVI.00253-07. View

Matsuyama S, Ujike M, Morikawa S, Tashiro M, Taguchi F . Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proc Natl Acad Sci U S A. 2005; 102(35):12543-7. PMC: 1194915. DOI: 10.1073/pnas.0503203102. View

Rota P, Oberste M, Monroe S, Nix W, Campagnoli R, Icenogle J . Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003; 300(5624):1394-9. DOI: 10.1126/science.1085952. View

Earp L, Delos S, Netter R, Bates P, White J . The avian retrovirus avian sarcoma/leukosis virus subtype A reaches the lipid mixing stage of fusion at neutral pH. J Virol. 2003; 77(5):3058-66. PMC: 149735. DOI: 10.1128/jvi.77.5.3058-3066.2003. View

Medinas R, Lambert D, Tompkins W . C-Terminal gp40 peptide analogs inhibit feline immunodeficiency virus: cell fusion and virus spread. J Virol. 2002; 76(18):9079-86. PMC: 136458. DOI: 10.1128/jvi.76.18.9079-9086.2002. View

Jahn R, Lang T, Sudhof T . Membrane fusion. Cell. 2003; 112(4):519-33. DOI: 10.1016/s0092-8674(03)00112-0. View

Yuan K, Yi L, Chen J, Qu X, Qing T, Rao X . Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein. Biochem Biophys Res Commun. 2004; 319(3):746-52. PMC: 7111000. DOI: 10.1016/j.bbrc.2004.05.046. View

Ksiazek T, Erdman D, Goldsmith C, Zaki S, Peret T, Emery S . A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003; 348(20):1953-66. DOI: 10.1056/NEJMoa030781. View

10.

Bosch B, Martina B, van der Zee R, Lepault J, Haijema B, Versluis C . Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc Natl Acad Sci U S A. 2004; 101(22):8455-60. PMC: 420415. DOI: 10.1073/pnas.0400576101. View

11.

Wang E, Sun X, Qian Y, Zhao L, Tien P, Gao G . Both heptad repeats of human respiratory syncytial virus fusion protein are potent inhibitors of viral fusion. Biochem Biophys Res Commun. 2003; 302(3):469-75. DOI: 10.1016/s0006-291x(03)00197-9. View

12.

Matsuyama S, Delos S, White J . Sequential roles of receptor binding and low pH in forming prehairpin and hairpin conformations of a retroviral envelope glycoprotein. J Virol. 2004; 78(15):8201-9. PMC: 446138. DOI: 10.1128/JVI.78.15.8201-8209.2004. View

13.

Rapaport D, Ovadia M, Shai Y . A synthetic peptide corresponding to a conserved heptad repeat domain is a potent inhibitor of Sendai virus-cell fusion: an emerging similarity with functional domains of other viruses. EMBO J. 1995; 14(22):5524-31. PMC: 394666. DOI: 10.1002/j.1460-2075.1995.tb00239.x. View

14.

YOUNG J, Li D, Abramowitz M, Morrison T . Interaction of peptides with sequences from the Newcastle disease virus fusion protein heptad repeat regions. J Virol. 1999; 73(7):5945-56. PMC: 112656. DOI: 10.1128/JVI.73.7.5945-5956.1999. View

15.

Chan W, Chuang C, Yeh S, Chang M, Chen S . Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus. J Virol. 2006; 80(7):3225-37. PMC: 1440416. DOI: 10.1128/JVI.80.7.3225-3237.2006. View

16.

Otaka A, Nakamura M, Nameki D, Kodama E, Uchiyama S, Nakamura S . Remodeling of gp41-C34 peptide leads to highly effective inhibitors of the fusion of HIV-1 with target cells. Angew Chem Int Ed Engl. 2002; 41(16):2937-40. DOI: 10.1002/1521-3773(20020816)41:16<2937::AID-ANIE2937>3.0.CO;2-J. View

17.

Supekar V, Bruckmann C, Ingallinella P, Bianchi E, Pessi A, Carfi A . Structure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein. Proc Natl Acad Sci U S A. 2004; 101(52):17958-63. PMC: 539766. DOI: 10.1073/pnas.0406128102. View

18.

Follis K, York J, Nunberg J . Serine-scanning mutagenesis studies of the C-terminal heptad repeats in the SARS coronavirus S glycoprotein highlight the important role of the short helical region. Virology. 2005; 341(1):122-9. PMC: 7111819. DOI: 10.1016/j.virol.2005.07.005. View

19.

Drosten C, Gunther S, Preiser W, van der Werf S, Brodt H, Becker S . Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003; 348(20):1967-76. DOI: 10.1056/NEJMoa030747. View

20.

Joshi S, Dutch R, Lamb R . A core trimer of the paramyxovirus fusion protein: parallels to influenza virus hemagglutinin and HIV-1 gp41. Virology. 1998; 248(1):20-34. DOI: 10.1006/viro.1998.9242. View