کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8304164 | 1538383 | 2018 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chikungunya virus inhibition by peptidomimetic inhibitors targeting virus-specific cysteine protease
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کلمات کلیدی
FRET assayGTaseEDANSDabcylnsP2 proteaseRFUSFVSINVMTaseRdRpFECIPTGDMEMFBSCMCORFIMACDulbecco's modified Eagle's medium - Medal of Eagle اصلاح شده DulbeccoMTT - MTTRNA dependent RNA polymerase - RNA پلیمراز وابسته به RNAFluorescence resonance energy transfer - انتقال انرژی رزونانس FluorescenceFRET - انتقال انرژی رزونانسی فورسترisopropyl β-D-1-thiogalactopyranoside - ایزوپروپیل β-D-1-thiogalactopyranosideChikungunya fever - تب ChickenunyaAntiviral assay - تست ضد ویروسیfetal bovine serum - سرم جنین گاوopen reading frame - قاب خواندن بازMethyltransferase - متیل ترانسفرازProtease inhibitor - مهارکننده پروتئازRelative Fluorescence Units - واحد فلورسانس نسبیChikungunya virus - ویروس ChikungunyaSemliki Forest virus - ویروس Semliki جنگلSindbis virus - ویروس SindbisCHIKV - چیکوCarboxymethyl cellulose - کربوکسی متیل سلولزimmobilized metal affinity chromatography - کروماتوگرافی وابسته به فلز متمرکزGuanylyltransferase - گویینیلترانسفراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Chikungunya virus (CHIKV), a mosquito-borne pathogenic virus that reemerged and caused epidemic in the Indian Ocean island of La Réunion, is a potential public health threat. Currently there is no antiviral drug or vaccine commercially available for the treatment of chikungunya fever, which necessitates the urge for an effective antiviral therapy for chikungunya treatment. In the present study, a FRET based protease assay was used to analyze the proteolytic activity of chikungunya nsP2 protease (CHIKV nsP2pro) - an essential viral enzyme, with fluorogenic substrate peptide. This protease assay was used to assess the inhibitory activity of Pep-I (MMsINC® database ID MMs03131094) and Pep-II (MMsINC® database ID MMs03927237), peptidomimetic compounds identified in a previous study by our group. Both compounds inhibited CHIKV nsP2pro with half maximal inhibition concentration (IC50) values of â¼34â¯Î¼M and â¼42â¯Î¼M, respectively. Kinetic studies showed that the inhibition constant (Ki) value is 33.34â¯Â±â¯2.53â¯Î¼M for Pep-I and 45.89â¯Â±â¯4.38â¯Î¼M for Pep-II. Additionally, these two compounds significantly inhibited CHIKV replication in BHK-21â¯cells at concentrations much lower than their cytotoxic concentrations. Intriguingly, these compounds did not show inhibitory effect on Sindbis virus. This suggests that Pep-I and Pep-II compounds identified as CHIKV nsP2 substrate peptidomimetics, specifically inhibit CHIKV replication.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 149, June 2018, Pages 51-61
Journal: Biochimie - Volume 149, June 2018, Pages 51-61
نویسندگان
Harvijay Singh, Rajat Mudgal, Manju Narwal, Ramanjit Kaur, Vedita Anand Singh, Anjali Malik, Madhulika Chaudhary, Shailly Tomar,