Virus Entry Inhibitors: Stopping the Enemy at the Gate

242 Pages·2022·7.919 MB·English

by  Shibo Jiang, Lu Lu

Advances in Experimental Medicine and Biology 1366
Shibo Jiang
Lu Lu   Editors
Virus Entry
Inhibitors
Stopping the Enemy at the Gate
Advances in Experimental Medicine
and Biology
Volume 1366
SeriesEditors
WimE.Crusio,InstitutdeNeurosciencesCognitivesetIntégratives
d’Aquitaine,CNRSandUniversityofBordeaux,PessacCedex,France
HaidongDong,DepartmentsofUrologyandImmunology
MayoClinic,Rochester,MN,USA
HeinfriedH.Radeke,InstituteofPharmacology&Toxicology
ClinicoftheGoetheUniversityFrankfurtMain,FrankfurtamMain,Hessen,
Germany
NimaRezaei,ResearchCenterforImmunodeficiencies,Children’sMedical
Center,TehranUniversityofMedicalSciences,Tehran,Iran
OrtrudSteinlein,InstituteofHumanGenetics
LMUUniversityHospital,Munich,Germany
JunjieXiao,CardiacRegenerationandAgeingLab,InstituteofCardiovas-
cularScience,SchoolofLifeScience,ShanghaiUniversity,Shanghai,China
Advances in Experimental Medicine and Biology provides a platform for
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Shibo Jiang Lu Lu
Editors
Virus Entry Inhibitors
Stopping the Enemy at the Gate
Editors
ShiboJiang LuLu
KeyLaboratoryofMedicalMolecular KeyLaboratoryofMedicalMolecular
Virology(MOE/NHC/CAMS) Virology(MOE/NHC/CAMS)
SchoolofBasicMedical SchoolofBasicMedical
Sciences,InstituteofInfectiousDisease Sciences,InstituteofInfectiousDisease
andBiosecurity,FudanUniversity andBiosecurity,FudanUniversity
Shanghai,China Shanghai,China
ISSN0065-2598 ISSN2214-8019 (electronic)
AdvancesinExperimentalMedicineandBiology
ISBN978-981-16-8701-3 ISBN978-981-16-8702-0 (eBook)
https://doi.org/10.1007/978-981-16-8702-0
#SpringerNatureSingaporePteLtd.2022
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Preface
Virusentryintothehosttargetcellisthefirststepoftheviralreplicationcycle.
It isinitiatedbytheattachmentoftheviral particle tothetargetcellthrough
specificinteractionbetweentheviralsurfaceprotein(s)andreceptor(s)onthe
host cell. This interaction triggers the conformation changes of the viral
surface protein(s), resulting in entry, via membrane fusion or endocytosis,
oftheviralgeneticmaterialsintothehostcellforreplication.
Virusentryinhibitorsareantiviralagentsthatblockviralentryintothehost
cell,includingthosethatbindviralsurfaceproteins,interferewithinteraction
between viral and host proteins, inhibit viral protein-mediated plasma or
endosomalmembranefusion,orinactivatecell-freevirions.
In the early 1990s, Jiang and colleagues identified the first highly potent
humanimmunodeficiencyvirus(HIV)entryinhibitorderivedfromtheHIV-1
gp41 C-terminal heptad repeat (CHR) domain and the related patent was
licensed to Trimeris, Inc., which jointly with Roche Pharmaceuticals devel-
oped the first virus entry inhibitor-based anti-HIV peptide drug, enfuvirtide
(Fuzeon),approvedbytheUSFDAin2003.Sincethen,severalseriesofthe
smallmolecule-,peptide-,andprotein-basedvirusentryinhibitorshavebeen
orarebeingdevelopedagainstenvelopedviruses,includinghumanimmuno-
deficiency virus (HIV), severe acute respiratory syndrome coronavirus
(SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV),
severeacuterespiratorysyndromecoronavirus2(SARS-CoV-2),Ebolavirus
(EBOV), Hendra virus (HeV), Nipah virus (NiV), influenza virus (IFV),
parainfluenzavirus(PIV),Zikavirus(ZIKV),Denguevirus(DENV),hepati-
tis Cvirus (HCV),andhepatitis Bvirus (HBV),andnon-enveloped viruses,
such as human papillomavirus (HPV). Since many of these viruses, such as
SARS-CoV, SARS-CoV-2, EBOV, ZIKV, HeV, and NiV, can cause
outbreaks of highly pathogenic emerging infectious diseases, virus entry
inhibitorsagainsttheseviruseshavegreatpotentialtobeusedforthepreven-
tionandtreatmentoftheseinfectiousdiseases.
Inthisbook,wewilldiscusstheadvancesintheresearchanddevelopment
ofthesmallmolecule-,peptide-,andprotein-basedvirusentryinhibitorsasa
novel class of antiviral drugs for the treatment and prevention of viral
infection.
Theoretically, virus neutralizing antibodies should belong to the protein-
based virus entry inhibitors since they can neutralize viral infection by
blocking virus attachment to the receptor on the host cell, interfering with
v
vi Preface
virus-cell fusion or inhibiting virus entry into the host cell for replication.
Since several books about the viral neutralizing antibodies have been
published by Springer, this book contains no chapter mainly discussing the
viralneutralizingantibodies.
Many authorsfor thisbookareinthetoplistoftheexperts worldwidein
the fields of HIV fusion inhibitors (https://expertscape.com/ex/hiv+fusion
+inhibitors)andviralfusionproteins(http://expertscape.com/ex/viral+fusion
+proteins).
Weheartilyappreciatealltheauthorsfortheircontributionstothisbook.
Shanghai,China ShiboJiang
Shanghai,China LuLu
Acknowledgments
WewouldliketoacknowledgethesupportfromMs.LinXuattheSchoolof
Basic Medical Sciences, Fudan University, who provided project manage-
mentandeditorialsupporttobotheditorsandallthecontributingauthors.
Wealsoacknowledgethecontributionofallourpreviousandcurrentteam
members and colleagues to the research and development of virus entry
inhibitors at the New York Blood Center, including Drs. Li Zhang, Qian
Zhao,HongLu,WeiguoJing,XuxiaYan,XiaozhiLu,ShuwenLiu,Yuxian
He, Lanying Du, Chungen Pan, Yuan Shui, Zhi Qi, Dongmei Cai, Xi Chen,
Xiaowen Yu, Xiujuan Zhang, Zhonghua Liu, Lifeng Cai, Lin Li, Suiyi Tan,
JieYang,CuiqingMa,NaruZhang,ChenglaiXia,TongXiang,WanboTai,
Yaning Gao, Dong Zhu, Ye Li, Jan Tang, A. Robert Neurath, Asim
K.Debnath,JinkuiNiu,andJamesFarmar;andthoseattheFudanUniversity,
includingDrs.QianWang,WeiXu, LingXu, ShuaiXia,ShanSu,Zezhong
Liu,FeiYu,QiLiu,ZhiwuSun,BiaoHe,WenLi,HaoyangLi,YufengYu,
QianqianQi,PeiyuLi,YuMeng,WenwenBi,YuhongFu,CongWang,Lulu
Si, Xiaojie Zhu, Yanyan Dai, Wenqian Yang, Chen Hua, Yuchen Qu, Miao
Cao,JiayiTang,XinlingWang,YanxingCai,JingPu,XiaojieSu,Qiaoshuai
Lan, Jie Zhou, Lijue Wang, Qianyu Duan, Najing Cao, Lixiao Xing, Fanke
Jiao,TianyuLu,TianleiYing,JingheHuang,QiaoWang,andYouhuaXie.
Wethankourcollaboratorswhomakecontributiontothestudiesonvirus
entryinhibitors,includingDrs.YinghuaChen,JiWang,PeiTong,Xiaowen
Yu, Yun Zhu, Hengwen Yang, Peng Zuo, and Fan Wu at Tsinghua Univer-
sity; Drs. Keliang Liu, Lan Xie, Song Li, Xiaoyang He, Weiguo Shi, Qiyan
Jia,andChaoWangattheBeijingInstituteofPharmacologyandToxicology;
Drs. Qiuyun Dai and Mingxing Dong at the Beijing Institute of Biotechnol-
ogy;Drs.YusenZhou,GuangjieZhao,ShihuiSun,andChengfengQinatthe
Beijing Institute of Microbiology and Epidemiology; Drs. Shuguang Wu,
Ruitao Zhang, Xiaoning Yu, Haitao Wang, Jiping Shao, and Jiayin Qiu at
the Southern Medical University; Drs. Bojian Zheng, Kwok-Yung Yuen,
Jasper Fuk-Woo Chan, Hanjun Zhao, Shuofeng Yuan, Jie Zhou, Kelvin
K. W. To, and Richard Kao at the University of Hong Kong; Drs. Gengfu
Xiao, Zhengli Shi, Huiming Yan, and Xi Zhou at the Wuhan Institute of
Microbiology;Drs.YimingShaoandLiyingMaatChinaCDC;andDrs.Min
Lu, Yichiel Shai, Andrew D. Hamilton, Justin T Ernst, Jianfeng Cai, Frank
Kirchhoff, Jan Münch, Zhikai Xu, Dominique Schols, Erik De Clercq,
vii
viii Acknowledgments
DimiterS Dimitrov,Robert Blumenthal,Carol D.Weiss,Ding-KwoChang,
YunLiao,LaixiWang,PoTian,YibangChen,CarlosREscalante,Chien-Te
K.Tseng,Zhi-hongJiang,andAlanRKatritzky.
Contents
1 VirusEntryInhibitors:Past,Present,andFuture. . . . . . . 1
ShanSu,WeiXu,andShiboJiang
2 Peptide-BasedHIVEntryInhibitors. . . . . . . . . . . . . . . . . 15
JingPu,QianWang,andShiboJiang
3 Small-MoleculeHIVEntryInhibitorsTargeting
gp120andgp41. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
FeiYuandShiboJiang
4 TheGenesisandFutureProspectsofSmallMolecule
HIV-1AttachmentInhibitors. . . . . . . . . . . . . . . . . . . . . . . 45
TaoWang,JohnF.Kadow,NicholasA.Meanwell,
andMarkKrystal
5 EndogenousPeptideInhibitorsofHIVEntry. . . . . . . . . . 65
MirjaHarms,ManuelHayn,FabianZech,FrankKirchhoff,
andJanMünch
6 Peptide-BasedDualHIVandCoronavirusEntry
Inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
HuanWangandChaoWang
7 CoronavirusEntryInhibitors. . . . . . . . . . . . . . . . . . . . . . 101
QiaoshuaiLan,ShuaiXia,andLuLu
8 InfluenzaVirusEntryinhibitors. . . . . . . . . . . . . . . . . . . . 123
JieYangandShuwenLiu
9 Broad-spectrumRespiratoryVirusEntryInhibitors. . . . . 137
HanjunZhaoandKwok-YungYuen
10 EbolaVirusEntryInhibitors. . . . . . . . . . . . . . . . . . . . . . . 155
RuikunDu,QinghuaCui,MichaelCaffrey,andLijunRong
11 FlavivirusEntryInhibitors. . . . . . . . . . . . . . . . . . . . . . . . 171
YufengYu,LuluSi,andYuMeng
12 EntryInhibitorsofHepatitisBandDViruses. . . . . . . . . . 199
YangYangandYouhuaXie
ix