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Therefore, it is imperative to develop potent anti-IAV drugs with different modes of action to currently available drugs. Herein, we show a new class of antiviral peptides generated by conjugating two known short antiviral peptides: part-1 (named Jp with the sequence of ARLPR) and part-2 (named Hp with the sequence of KKWK). The new peptides were thus created by hybridization of these two domains at C- and N- termini, respectively. The anti-IAV screening results identified that C20-Jp-Hp was the most potent peptide with IC<jats:sub>50<\/jats:sub> value of 0.53\u2009\u03bcM against A\/Puerto Rico\/8\/34 (H1N1) strain. Interestingly, these new peptides display lower toxicities toward mammalian cells and higher therapeutic indices than their prototypes. In addition, the mechanism of action of C20-Jp-Hp was extensively investigated.<\/jats:p>","DOI":"10.1038\/srep22790","type":"journal-article","created":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T10:26:35Z","timestamp":1457432795000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A \u201cbuilding block\u201d approach to the new influenza A virus entry inhibitors with reduced cellular toxicities"],"prefix":"10.1038","volume":"6","author":[{"given":"Dongguo","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangkun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,8]]},"reference":[{"key":"BFsrep22790_CR1","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1038\/nrd2175","volume":"5","author":"E De Clercq","year":"2006","unstructured":"De Clercq, E. 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