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Article: Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus

TitleSynthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus
Authors
Issue Date2005
PublisherInternational Medical Press. The Journal's web site is located at http://www.intmedpress.com/Journals/AVT/journals_avt_home.cfm
Citation
Antiviral Therapy, 2005, v. 10 n. 3, p. 393-403 How to Cite?
AbstractA novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals to humans. Comparison of the viral genomes indicated that sequence variation between animal and human isolates existed mainly in the spike (S) gene. We hypothesized that these variations may underlie a change of binding specificity of the S protein to the host cells, permitting viral transmission from animals to humans. Here we report that four 20-mer synthetic peptides (S protein fragments), designed to span these sequence variation hotspots, exhibited significant antiviral activities in a cell line. SARS-CoV infectivity was reduced over 10000-fold through pre-incubation with two of these peptides, while it was completely inhibited in the presence of three peptides. Molecular modelling of the SARS-CoV peplomer suggests that three of these antiviral peptides map to the interfaces between the three monomers of the trimeric peplomer rather than the heptad repeat region from which short peptides are known to inhibit viral entry. Our results revealed novel regions in the spike protein that can be targeted to inhibit viral infection. The peptides identified in this study could be further developed into antiviral drugs. © 2005 International Medical Press.
Persistent Identifierhttp://hdl.handle.net/10722/68047
ISSN
2015 Impact Factor: 2.916
2015 SCImago Journal Rankings: 1.361
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorHe, MLen_HK
dc.contributor.authorSun, Hen_HK
dc.contributor.authorDu, Len_HK
dc.contributor.authorZheng, Yen_HK
dc.contributor.authorWong, KLen_HK
dc.contributor.authorChen, Hen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorLu, Len_HK
dc.contributor.authorTanner, JAen_HK
dc.contributor.authorWatt, RMen_HK
dc.contributor.authorNiccolai, Nen_HK
dc.contributor.authorBernini, Aen_HK
dc.contributor.authorSpiga, Oen_HK
dc.contributor.authorWoo, PCYen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorYuen, KYen_HK
dc.contributor.authorHuang, JDen_HK
dc.date.accessioned2010-09-06T06:00:50Z-
dc.date.available2010-09-06T06:00:50Z-
dc.date.issued2005en_HK
dc.identifier.citationAntiviral Therapy, 2005, v. 10 n. 3, p. 393-403en_HK
dc.identifier.issn1359-6535en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68047-
dc.description.abstractA novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals to humans. Comparison of the viral genomes indicated that sequence variation between animal and human isolates existed mainly in the spike (S) gene. We hypothesized that these variations may underlie a change of binding specificity of the S protein to the host cells, permitting viral transmission from animals to humans. Here we report that four 20-mer synthetic peptides (S protein fragments), designed to span these sequence variation hotspots, exhibited significant antiviral activities in a cell line. SARS-CoV infectivity was reduced over 10000-fold through pre-incubation with two of these peptides, while it was completely inhibited in the presence of three peptides. Molecular modelling of the SARS-CoV peplomer suggests that three of these antiviral peptides map to the interfaces between the three monomers of the trimeric peplomer rather than the heptad repeat region from which short peptides are known to inhibit viral entry. Our results revealed novel regions in the spike protein that can be targeted to inhibit viral infection. The peptides identified in this study could be further developed into antiviral drugs. © 2005 International Medical Press.en_HK
dc.languageengen_HK
dc.publisherInternational Medical Press. The Journal's web site is located at http://www.intmedpress.com/Journals/AVT/journals_avt_home.cfmen_HK
dc.relation.ispartofAntiviral Therapyen_HK
dc.titleSynthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirusen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1359-6535&volume=10&spage=393&epage=403&date=2005&atitle=Synthetic+peptides+outside+the+spike+protein+heptad+repeat+regions+as+potent+inhibitors+of+SARS-associated+coronavirusen_HK
dc.identifier.emailZheng, BJ: bzheng@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailSun, H: hsun@hku.hken_HK
dc.identifier.emailChen, H: hlchen@hku.hken_HK
dc.identifier.emailTanner, JA: jatanner@hku.hken_HK
dc.identifier.emailWatt, RM: rmwatt@hku.hken_HK
dc.identifier.emailWoo, PCY: pcywoo@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hken_HK
dc.identifier.emailHuang, JD: jdhuang@hku.hken_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authoritySun, H=rp00777en_HK
dc.identifier.authorityChen, H=rp00383en_HK
dc.identifier.authorityTanner, JA=rp00495en_HK
dc.identifier.authorityWatt, RM=rp00043en_HK
dc.identifier.authorityWoo, PCY=rp00430en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid15918330-
dc.identifier.scopuseid_2-s2.0-20444474961en_HK
dc.identifier.hkuros99113en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-20444474961&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue3en_HK
dc.identifier.spage393en_HK
dc.identifier.epage403en_HK
dc.identifier.isiWOS:000231962800003-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridHe, ML=35080389700en_HK
dc.identifier.scopusauthoridSun, H=7404827446en_HK
dc.identifier.scopusauthoridDu, L=8686996200en_HK
dc.identifier.scopusauthoridZheng, Y=24829986900en_HK
dc.identifier.scopusauthoridWong, KL=7404758889en_HK
dc.identifier.scopusauthoridChen, H=26643315400en_HK
dc.identifier.scopusauthoridChen, Y=35227073300en_HK
dc.identifier.scopusauthoridLu, L=8686996700en_HK
dc.identifier.scopusauthoridTanner, JA=35513993000en_HK
dc.identifier.scopusauthoridWatt, RM=7102907536en_HK
dc.identifier.scopusauthoridNiccolai, N=7003440494en_HK
dc.identifier.scopusauthoridBernini, A=7004103621en_HK
dc.identifier.scopusauthoridSpiga, O=6603012863en_HK
dc.identifier.scopusauthoridWoo, PCY=7201801340en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK

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