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However, increasing evidence suggests that the brain has to continuously produce excessive A\u03b2 to efficaciously prevent pathogenic micro-organism infections, which induces and accelerates the disease process of AD. Meanwhile, A\u03b2 exhibits activity against herpes simplex virus type\u00a01 (HSV-1) and influenza A virus (IAV) replication, but not against other neurotropic viruses. Enterovirus A71 (EV-A71) is the most important neurotropic enterovirus in the post-polio era. Given the limitation of existing research on the relationship between A\u03b2 and other virus infections, this study aimed to investigate the potent activity of A\u03b2 on EV-A71 infection and extended the potential function of A\u03b2 in other unenveloped viruses may be linked to Alzheimer's disease or infectious neurological diseases.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A\u03b2 peptides 1\u201342 are a major pathological factor of senile plaques in Alzheimer\u2019s disease (AD). Thus, we utilized A\u03b2<jats:sub>1\u201342<\/jats:sub> as a test subject to perform our study. The production of monomer A\u03b2<jats:sub>1\u201342<\/jats:sub> and their high-molecular oligomer accumulations in neural cells were detected by immunofluorescence assay, ELISA, or Western blot assay. The inhibitory activity of A\u03b2<jats:sub>1\u201342<\/jats:sub> peptides against EV-A71 in vitro was detected by Western blot analysis or qRT-PCR. The mechanism of A\u03b2<jats:sub>1\u201342<\/jats:sub> against EV-A71 replication was analyzed by time-of-addition assay, attachment inhibition assay, pre-attachment inhibition analysis, viral-penetration inhibition assay, TEM analysis of virus agglutination, and pull-down assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that EV-A71 infection induced A\u03b2 production and accumulation in SH-SY5Y cells. We also revealed for the first time that A\u03b2<jats:sub>1\u201342<\/jats:sub> efficiently inhibited the RNA level of EV-A71 VP1, and the protein levels of VP1, VP2, and nonstructural protein 3AB in SH-SY5Y, Vero, and human rhabdomyosarcoma (RD) cells. Mechanistically, we demonstrated that A\u03b2<jats:sub>1\u201342<\/jats:sub> primarily targeted the early stage of EV-A71 entry to inhibit virus replication by binding virus capsid protein VP1 or scavenger receptor class B member 2. Moreover, A\u03b2<jats:sub>1\u201342<\/jats:sub> formed non-enveloped EV-A71 particle aggregates within a certain period and bound to the capsid protein VP1, which partially caused A\u03b2<jats:sub>1\u201342<\/jats:sub> to prevent viruses from infecting cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings unveiled that A\u03b2<jats:sub>1\u201342<\/jats:sub> effectively inhibited nonenveloped EV-A71 by targeting the early phase of an EV-A71 life cycle, thereby extending the potential function of A\u03b2 in other non-envelope viruses linked to infectious neurological diseases.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12985-022-01882-3","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T07:02:37Z","timestamp":1663657357000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects and mechanism of A\u03b21\u221242 on EV-A71 replication"],"prefix":"10.1186","volume":"19","author":[{"given":"Ming","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boming","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"1882_CR1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41582-020-0323-9","volume":"16","author":"RF Itzhaki","year":"2020","unstructured":"Itzhaki RF, Golde TE, Heneka MT, Readhead B. 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