{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:19:13Z","timestamp":1790299153894,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Recently, Zika virus (ZIKV) has attracted much attention in consideration of its association with severe neurological complications including fetal microcephaly. However, there are currently no prophylactic vaccines or therapeutic drugs approved for clinical treatments of ZIKV infection. To determine the potential anti-ZIKV inhibitors, we screened a library of clinical drugs with good safety profiles. Erythromycin estolate (Ery-Est), one of the macrolide antibiotics, was found to effectively inhibit ZIKV infection in different cell types and significantly protect A129 mice from ZIKV-associated neurological signs and mortality. Through further investigation, Ery-Est was verified to inhibit ZIKV entry by disrupting the integrity of the viral membrane which resulted in the loss of ZIKV infectivity. Furthermore, Ery-Est also showed inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Thus, Ery-Est may be a promising drug for patients with ZIKV infection, particularly pregnant women.<\/jats:p>","DOI":"10.3390\/v11111064","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T11:25:56Z","timestamp":1573817156000},"page":"1064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Erythromycin Estolate Inhibits Zika Virus Infection by Blocking Viral Entry as a Viral Inactivator"],"prefix":"10.3390","volume":"11","author":[{"given":"Xiaohuan","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7896-4182","authenticated-orcid":false,"given":"Shuai","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-0391","authenticated-orcid":false,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus. I. Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R Soc. Trop. Med. Hyg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0035-9203(54)90006-1","article-title":"Zika virus: A report on three cases of human infection during an epidemic of jaundice in Nigeria","volume":"48","author":"Macnamara","year":"1954","journal-title":"Trans. R Soc. Trop. Med. Hyg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"O595","DOI":"10.1111\/1469-0691.12707","article-title":"Rapid spread of emerging Zika virus in the Pacific area","volume":"20","author":"Musso","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S0140-6736(16)00625-5","article-title":"Zika virus infection in French Polynesia","volume":"387","author":"Jouannic","year":"2016","journal-title":"Lancet"},{"key":"ref_5","unstructured":"(2019, November 12). Zika Virus Outbreaks in the Americas, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26552108\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"i657","DOI":"10.1136\/bmj.i657","article-title":"Zika virus is a global public health emergency, declares WHO","volume":"352","author":"Gulland","year":"2016","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1038\/s41467-018-07782-x","article-title":"Routes of Zika virus dissemination in the testis and epididymis of immunodeficient mice","volume":"9","author":"Tsetsarkin","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_8","first-page":"e005161","article-title":"Corrigendum: Optic neuropathy and congenital glaucoma associated with probable Zika virus infection in Venezuelan patients","volume":"5","author":"Pettito","year":"2018","journal-title":"JMM Case Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nrneurol.2016.30","article-title":"CNS infections: Zika virus infection could trigger Guillain-Barre syndrome","volume":"12","author":"Malkki","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1056\/NEJMc1602964","article-title":"Zika Virus Associated with Meningoencephalitis","volume":"374","author":"Carteaux","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1086\/429930","article-title":"Autosomal recessive primary microcephaly (MCPH): A review of clinical, molecular, and evolutionary findings","volume":"76","author":"Woods","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"i720","DOI":"10.1136\/bmj.i720","article-title":"Zika virus was transmitted by sexual contact in Texas, health officials report","volume":"352","author":"McCarthy","year":"2016","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"ofw175","DOI":"10.1093\/ofid\/ofw175","article-title":"Adenosine Analog NITD008 Is a Potent Inhibitor of Zika Virus","volume":"3","author":"Deng","year":"2016","journal-title":"Open Forum Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Delvecchio, R., Higa, L.M., Pezzuto, P., Valadao, A.L., Garcez, P.P., Monteiro, F.L., Loiola, E.C., Dias, A.A., Silva, F.J., and Aliota, M.T. (2016). Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models. Viruses, 8.","DOI":"10.1101\/051268"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.immuni.2017.02.012","article-title":"25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model","volume":"46","author":"Li","year":"2017","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.celrep.2016.12.068","article-title":"Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus","volume":"18","author":"Rausch","year":"2017","journal-title":"Cell Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ijid.2019.01.041","article-title":"Macrolides in critically ill patients with Middle East Respiratory Syndrome","volume":"81","author":"Arabi","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"528568","DOI":"10.1155\/2012\/528568","article-title":"Clarithromycin suppresses human respiratory syncytial virus infection-induced Streptococcus pneumoniae adhesion and cytokine production in a pulmonary epithelial cell line","volume":"2012","author":"Yokota","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dong, S., and Kang, S. (2019). Identification of anti-flaviviral drugs with mosquitocidal and anti-Zika virus activity in Aedes aegypti. PLoS Negl. Trop. Dis.","DOI":"10.1371\/journal.pntd.0007681"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6","DOI":"10.4172\/1948-5964.1000173","article-title":"Azithromycin Inhibits the Replication of Zika Virus","volume":"10","author":"Bosseboeuf","year":"2018","journal-title":"J. Antivir. Antiretrovir."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Iannetta, M., Ippolito, G., and Nicastri, E. (2017). Azithromycin Shows Anti-Zika Virus Activity in Human Glial Cells. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.01152-17"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14408","DOI":"10.1073\/pnas.1618029113","article-title":"Zika virus cell tropism in the developing human brain and inhibition by azithromycin","volume":"113","author":"Retallack","year":"2016","journal-title":"Am. Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wu, Y.H., Tseng, C.K., Lin, C.K., Wei, C.K., Lee, J.C., and Young, K.C. (2018). ICR suckling mouse model of Zika virus infection for disease modeling and drug validation. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006848"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s11427-016-5043-4","article-title":"Isolation, identification and genomic characterization of the Asian lineage Zika virus imported to China","volume":"59","author":"Deng","year":"2016","journal-title":"Sci. China Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lahon, A., Arya, R.P., Kneubehl, A.R., Vogt, M.B., Dailey Garnes, N.J., and Rico-Hesse, R. (2016). Characterization of a Zika Virus Isolate from Colombia. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0005019"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Deng, Y.Q., Dai, J.X., Ji, G.H., Jiang, T., Wang, H.J., Yang, H.O., Tan, W.L., Liu, R., Yu, M., and Qin, C.F. (2011). A broadly flavivirus cross-neutralizing monoclonal antibody that recognizes a novel epitope within the fusion loop of E protein. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016059"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15672","DOI":"10.1038\/ncomms15672","article-title":"A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses","volume":"8","author":"Yu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Xie, J., Liu, J.H., Liu, H., Liao, X.Z., Chen, Y., Lin, M.G., Gu, Y.Y., Liu, T.L., Wang, D.M., and Ge, H. (2016). Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2921-x"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11461","DOI":"10.1038\/s41598-019-47956-1","article-title":"Lipophilic statins inhibit Zika virus production in Vero cells","volume":"9","author":"Espano","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.antiviral.2017.03.014","article-title":"Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding","volume":"142","author":"Mounce","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1038\/ncomms4067","article-title":"Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor","volume":"5","author":"Lu","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/1743-422X-10-266","article-title":"A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV","volume":"10","author":"Zhao","year":"2013","journal-title":"Virol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eaau8408","DOI":"10.1126\/sciadv.aau8408","article-title":"Triterpenoids manipulate a broad range of virus-host fusion via wrapping the HR2 domain prevalent in viral envelopes","volume":"4","author":"Si","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1742-4690-9-104","article-title":"A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains","volume":"9","author":"Lu","year":"2012","journal-title":"Retrovirology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lok, S.M., Costin, J.M., Hrobowski, Y.M., Hoffmann, A.R., Rowe, D.K., Kukkaro, P., Wimley, W.C., Isern, S., Rossmann, M.G., and Michael, S.F. (2012). Release of dengue virus genome induced by a peptide inhibitor. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050995"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Aliota, M.T., Caine, E.A., Walker, E.C., Larkin, K.E., Camacho, E., and Osorio, J.E. (2016). Characterization of Lethal Zika Virus Infection in AG129 Mice. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004750"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Li, S., Armstrong, N., Zhao, H., Hou, W., Liu, J., Chen, C., Zhong, C., Liu, C., Zhu, H., and Xia, N. (2018). Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System. Viruses, 10.","DOI":"10.3390\/v10010049"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1038\/emi.2016.99","article-title":"Differential cell line susceptibility to the emerging Zika virus: Implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs","volume":"5","author":"Chan","year":"2016","journal-title":"Emerg. Microbes Infect."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Conzelmann, C., Zou, M., Gross, R., Harms, M., Rocker, A., Riedel, C.U., Munch, J., and Muller, J.A. (2019). Storage-Dependent Generation of Potent Anti-ZIKV Activity in Human Breast Milk. Viruses, 11.","DOI":"10.3390\/v11070591"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.chom.2016.04.013","article-title":"Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody","volume":"19","author":"Dai","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"718","DOI":"10.3389\/fmicb.2019.00718","article-title":"Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid","volume":"10","author":"Park","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Raza, S., Abbas, G., and Azam, S.S. (2019). Screening pipeline for Flavivirus based Inhibitors for Zika Virus NS1. IEEE\/ACM Trans. Comput. Biol. Bioinform.","DOI":"10.1109\/TCBB.2019.2911081"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.3389\/fmicb.2018.03252","article-title":"Zika Virus: Origins, Pathological Action, and Treatment Strategies","volume":"9","author":"Gorshkov","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1128\/AAC.32.4.561","article-title":"Pharmacokinetic advantages of erythromycin estolate over ethylsuccinate as determined by high-pressure liquid chromatography","volume":"32","author":"Croteau","year":"1988","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Altunaiji, S., Kukuruzovic, R., Curtis, N., and Massie, J. (2007). Antibiotics for whooping cough (pertussis). Cochrane Database Syst. Rev., Cd004404.","DOI":"10.1002\/14651858.CD004404.pub3"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1542\/peds.114.1.e96","article-title":"Azithromycin is as effective as and better tolerated than erythromycin estolate for the treatment of pertussis","volume":"114","author":"Langley","year":"2004","journal-title":"Pediatrics."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Raynes-Greenow, C.H., Roberts, C.L., Bell, J.C., Peat, B., and Gilbert, G.L. (2004). Antibiotics for ureaplasma in the vagina in pregnancy. Cochrane Database Syst. Rev., Cd003767.","DOI":"10.1002\/14651858.CD003767.pub2"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cnur.2019.02.005","article-title":"Zika Virus and Pregnancy Concerns","volume":"54","author":"DeCocker","year":"2019","journal-title":"Nurs. Clin. N. Am."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/ANC.0000000000000557","article-title":"Zika Virus Infection: A Vector-Borne Threat to Pregnant Women and Infants","volume":"18","author":"Grazel","year":"2018","journal-title":"Adv. Neonatal Care"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1055\/s-0038-1648219","article-title":"Abortion in Cases of Zika Virus Congenital Infection","volume":"40","author":"Mota","year":"2018","journal-title":"Rev. Bras. Ginecol. Obstet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ebiom.2017.04.029","article-title":"Visual and Motor Deficits in Grown-up Mice with Congenital Zika Virus Infection","volume":"20","author":"Cui","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sakkas, H., Bozidis, P., Giannakopoulos, X., Sofikitis, N., and Papadopoulou, C. (2018). An update on sexual transmission of Zika virus. Pathogens, 7.","DOI":"10.3390\/pathogens7030066"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.celrep.2017.01.056","article-title":"Frequent Zika Virus Sexual Transmission and Prolonged Viral RNA Shedding in an Immunodeficient Mouse Model","volume":"18","author":"Duggal","year":"2017","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gunawardana, S.A., and Shaw, R.H. (2018). Cross-reactive dengue virus-derived monoclonal antibodies to Zika virus envelope protein: Panacea or Pandora\u2019s box?. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3572-0"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Li, M., Zhao, L., Zhang, C., Wang, X., Hong, W., Sun, J., Liu, R., Wang, J., Zhang, F., and Jin, X. (2018). Dengue immune sera enhance Zika virus infection in human peripheral blood monocytes through Fc gamma receptors. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200478"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.it.2016.08.006","article-title":"Dengue Antibody and Zika: Friend or Foe?","volume":"37","author":"Durbin","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coviro.2019.02.002","article-title":"Structural perspectives of antibody-dependent enhancement of infection of dengue virus","volume":"36","author":"Morrone","year":"2019","journal-title":"Curr. Opin. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature20564","article-title":"Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice","volume":"540","author":"Sapparapu","year":"2016","journal-title":"Nature"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/11\/1064\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:34:37Z","timestamp":1760189677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/11\/1064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,15]]},"references-count":58,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["v11111064"],"URL":"https:\/\/doi.org\/10.3390\/v11111064","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,15]]}}}