Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein

doi:10.1016/j.bbrc.2004.05.046

. 2004 Jul 2;319(3):746-52.

doi: 10.1016/j.bbrc.2004.05.046.

Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein

Kehu Yuan¹, Ling Yi, Jian Chen, Xiuxia Qu, Tingting Qing, Xi Rao, Pengfei Jiang, Jianhe Hu, Zikai Xiong, Yuchun Nie, Xuanling Shi, Wei Wang, Chen Ling, Xiaolei Yin, Keqiang Fan, Luhua Lai, Mingxiao Ding, Hongkui Deng

Affiliations

PMID: 15184046
PMCID: PMC7111000
DOI: 10.1016/j.bbrc.2004.05.046

Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein

Kehu Yuan et al. Biochem Biophys Res Commun. 2004.

. 2004 Jul 2;319(3):746-52.

doi: 10.1016/j.bbrc.2004.05.046.

Authors

Affiliation

¹ Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, PR China.

PMID: 15184046
PMCID: PMC7111000
DOI: 10.1016/j.bbrc.2004.05.046

Abstract

Heptad repeat regions (HR1 and HR2) are highly conserved sequences located in the glycoproteins of enveloped viruses. They form a six-helix bundle structure and are important in the process of virus fusion. Peptides derived from the HR regions of some viruses have been shown to inhibit the entry of these viruses. SARS-CoV was also predicted to have HR1 and HR2 regions in the S2 protein. Based on this prediction, we designed 25 peptides and screened them using a HIV-luc/SARS pseudotyped virus assay. Two peptides, HR1-1 and HR2-18, were identified as potential inhibitors, with EC(50) values of 0.14 and 1.19microM, respectively. The inhibitory effects of these peptides were validated by the wild-type SARS-CoV assay. HR1-1 and HR2-18 can serve as functional probes for dissecting the fusion mechanism of SARS-CoV and also provide the potential of further identifying potent inhibitors for SARS-CoV entry.

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Figures

**Fig. 1**
Peptide design and purification. (A) Prediction output of Learncoil-VMF program for SARS-CoV spike protein. The HR1 and HR2 are indicated by arrowhead. (B) Fifteen percent SDS–PAGE analysis of purified peptides. Samples (7.5 μl) were loaded for each lane. The gel was stained by Coomassie blue.

**Fig. 2**
The inhibitory activities of the peptides for HIV-luc/SARS pseudotyped virus infection. (A) Sequence location of the peptides HR1-1 and HR2-18 (italics and underlined). (B) Peptides HR1-1 and HR2-18 can inhibit the HIV-luc/SARS pseudotyped virus infection with EC₅₀ value of 0.14 and 1.19 μM while HR2-10 showed little effect. The experiments were repeated three times and the data here show the average values.

**Fig. 3**
The inhibition activities of HR1-1 and HR2-18 for wild-typed SARS-CoV infection. Inhibitory effects of HR1-1, HR2-10, and HR2-18 were tested by MTT assay. The EC₅₀ of HR1-1 (triangle) was 3.68 μM and the EC₅₀ of HR2-18 (square) was 5.22 μM; HR2-10 (diamond) showed no effect. Similar results were obtained in three independent experiments.

**Fig. 4**
Secondary structure of HR1-1, HR2-18, and HR1-1 and HR2-18 complex by circular dichroism (CD) analysis. CD spectra of the peptides were analyzed at 25 °C in PBS. Spectra of HR1-1 (solid line) and HR2-18 (dashed line) showed a clear negative peak at 208 nm; the spectra of HR1-1 and HR2-18 complex (dotted line) showed a clear negative peak at 208 nm and small negative peaks at 220 nm, which is indicative of α-helix characteristics.

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References

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[1] Tsang K.W, Ho P.L, Ooi G.C, Yee W.K, Wang T, Chan-Yeung M, Lam W.K, Seto W.H, Yam L.Y, Cheung T.M, Wong P.C, Lam B, Ip M.S, Chan J, Yuen K.Y, Lai K.N. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 2003;348:1977–1985. - PubMed

[2] Tsang K.W, Ho P.L, Ooi G.C, Yee W.K, Wang T, Chan-Yeung M, Lam W.K, Seto W.H, Yam L.Y, Cheung T.M, Wong P.C, Lam B, Ip M.S, Chan J, Yuen K.Y, Lai K.N. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 2003;348:1977–1985. - PubMed

[3] Poutanen S.M, Low D.E, Henry B, Finkelstein S, Rose D, Green K, Tellier R, Draker R, Adachi D, Ayers M, Chan A.K, Skowronski D.M, Salit I, Simor A.E, Slutsky A.S, Doyle P.W, Krajden M, Petric M, Brunham R.C, McGeer A.J. Identification of severe acute respiratory syndrome in Canada. N. Engl. J. Med. 2003;348:1995–2005. - PubMed

[4] Poutanen S.M, Low D.E, Henry B, Finkelstein S, Rose D, Green K, Tellier R, Draker R, Adachi D, Ayers M, Chan A.K, Skowronski D.M, Salit I, Simor A.E, Slutsky A.S, Doyle P.W, Krajden M, Petric M, Brunham R.C, McGeer A.J. Identification of severe acute respiratory syndrome in Canada. N. Engl. J. Med. 2003;348:1995–2005. - PubMed

[5] Rota P.A, Oberste M.S, Monroe S.S, Nix W.A, Campagnoli R, Icenogle J.P, Penaranda S, Bankamp B, Maher K, Chen M.H, Tong S, Tamin A, Lowe L, Frace M, DeRisi J.L, Chen Q, Wang D, Erdman D.D, Peret T.C, Burns C, Ksiazek T.G, Rollin P.E, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, Olsen-Rasmussen M, Fouchier R, Gunther S, Osterhaus A.D, Drosten C, Pallansch M.A, Anderson L.J, Bellini W.J. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003;300:1394–1399. - PubMed

[6] Rota P.A, Oberste M.S, Monroe S.S, Nix W.A, Campagnoli R, Icenogle J.P, Penaranda S, Bankamp B, Maher K, Chen M.H, Tong S, Tamin A, Lowe L, Frace M, DeRisi J.L, Chen Q, Wang D, Erdman D.D, Peret T.C, Burns C, Ksiazek T.G, Rollin P.E, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, Olsen-Rasmussen M, Fouchier R, Gunther S, Osterhaus A.D, Drosten C, Pallansch M.A, Anderson L.J, Bellini W.J. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003;300:1394–1399. - PubMed

[7] Drosten C, Gunther S, Preiser W, van der Werf S, Brodt H.R, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier R.A, Berger A, Burguiere A.M, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra J.C, Muller S, Rickerts V, Sturmer M, Vieth S, Klenk H.D, Osterhaus A.D, Schmitz H, Doerr H.W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348:1967–1976. - PubMed

[8] Drosten C, Gunther S, Preiser W, van der Werf S, Brodt H.R, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier R.A, Berger A, Burguiere A.M, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra J.C, Muller S, Rickerts V, Sturmer M, Vieth S, Klenk H.D, Osterhaus A.D, Schmitz H, Doerr H.W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348:1967–1976. - PubMed

[9] Marra M.A, Jones S.J, Astell C.R, Holt R.A, Brooks-Wilson A, Butterfield Y.S, Khattra J, Asano J.K, Barber S.A, Chan S.Y, Cloutier A, Coughlin S.M, Freeman D, Girn N, Griffith O.L, Leach S.R, Mayo M, McDonald H, Montgomery S.B, Pandoh P.K, Petrescu A.S, Robertson A.G, Schein J.E, Siddiqui A, Smailus D.E, Stott J.M, Yang G.S, Plummer F, Andonov A, Artsob H, Bastien N, Bernard K, Booth T.F, Bowness D, Czub M, Drebot M, Fernando L, Flick R, Garbutt M, Gray M, Grolla A, Jones S, Feldmann H, Meyers A, Kabani A, Li Y, Normand S, Stroher U, Tipples G.A, Tyler S, Vogrig R, Ward D, Watson B, Brunham R.C, Krajden M, Petric M, Skowronski D.M, Upton C, Roper R.L. The Genome sequence of the SARS-associated coronavirus. Science. 2003;300:1399–1404. - PubMed

[10] Marra M.A, Jones S.J, Astell C.R, Holt R.A, Brooks-Wilson A, Butterfield Y.S, Khattra J, Asano J.K, Barber S.A, Chan S.Y, Cloutier A, Coughlin S.M, Freeman D, Girn N, Griffith O.L, Leach S.R, Mayo M, McDonald H, Montgomery S.B, Pandoh P.K, Petrescu A.S, Robertson A.G, Schein J.E, Siddiqui A, Smailus D.E, Stott J.M, Yang G.S, Plummer F, Andonov A, Artsob H, Bastien N, Bernard K, Booth T.F, Bowness D, Czub M, Drebot M, Fernando L, Flick R, Garbutt M, Gray M, Grolla A, Jones S, Feldmann H, Meyers A, Kabani A, Li Y, Normand S, Stroher U, Tipples G.A, Tyler S, Vogrig R, Ward D, Watson B, Brunham R.C, Krajden M, Petric M, Skowronski D.M, Upton C, Roper R.L. The Genome sequence of the SARS-associated coronavirus. Science. 2003;300:1399–1404. - PubMed

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Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein

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Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein

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