کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2513171 1118398 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Recombinant chimeric lectins consisting of mannose-binding lectin and L-ficolin are potent inhibitors of influenza A virus compared with mannose-binding lectin
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Recombinant chimeric lectins consisting of mannose-binding lectin and L-ficolin are potent inhibitors of influenza A virus compared with mannose-binding lectin
چکیده انگلیسی

MBL structurally contains a type II-like collagenous domain and a carbohydrate recognition domain (CRD). We have recently generated three novel recombinant chimeric lectins (RCL), in which varying length of collagenous domain of mannose-binding lectin (MBL) is replaced with that of L-ficolin (L-FCN). CRD of MBL is used for target recognition because it has a broad spectrum in pathogen recognition compared with L-FCN. Results of our study demonstrate that these RCLs are potent inhibitors of influenza A virus (IAV). RCLs, against IAV, show dose-dependent activation of the lectin complement pathway, which is significantly higher than that of recombinant human MBL (rMBL). This activity is observed even without MBL-associated serine proteases (MASPs, provided by MBL deficient mouse sera), which have been thought to mediate complement activation. These observations suggest that RCLs are more efficient in associating with MASP-2, which predominantly mediates the activity. Yet, additional serum further increases the activity while RCL-mediated coagulation-like enzyme activities are diminished compared with rMBL, suggesting reduced association with MASP-1, which has been shown to mediate coagulation-like activity. These data suggest that RCLs may interfere less with host coagulation, which is advantageous to be a therapeutic drug. Importantly, these RCLs have surpassed rMBL for anti-viral activities, such as viral aggregation, reduction of viral hemagglutination (HA) and inhibition of virus-mediated HA and neuraminidase (NA) activities. These results are encouraging that novel RCLs could be used as anti-IAV agents with less side effect and that RCLs would be suitable candidates in developing a new anti-IAV therapy.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 81, Issue 3, 1 February 2011, Pages 388–395
نویسندگان
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