دورية
In silico strategies on prion pathogenic conversion and inhibition from PrPC–PrPSc
| العنوان: | In silico strategies on prion pathogenic conversion and inhibition from PrPC–PrPSc |
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| المؤلفون: | Pagadala, Nataraj S., Syed, Khajamohiddin, Bhat, Rakesh |
| المصدر: | Expert Opinion on Drug Discovery; March 2017, Vol. 12 Issue: 3 p241-248, 8p |
| مستخلص: | ABSTRACTIntroduction: To date, various therapeutic strategies identified numerous anti-prion compounds and antibodies that stabilize PrPC, block the conversion of PrPC-PrPScand increased effect on PrPScclearance. However, no suitable drug has been identified clinically so far due to the poor oral absorption, low blood–brain-barrier [BBB] penetration, and high toxicity. Although some of the drugs were proven to be effective in prion-infected cell culture and whole animal models, none of them increased the rate of survival compared to placebo.Areas covered: In this review, the authors highlight the importance of in silicoapproaches like molecular docking, virtual screening, pharmacophore analysis, molecular dynamics, QSAR, CoMFA and CoMSIA applied to detect molecular mechanisms of prion inhibition and conversion from PrPC-PrPSc.Expert opinion: Several in silicoapproaches combined with experimental studies have provided many structural and functional clues on the stability and physiological activity of prion mutants. Further, various studies of in silicoand in vivoapproaches were also shown to identify several new small organic anti-scrapie compounds to decrease the accumulation of PrPresin cell culture, inhibit the aggregation of a PrPCpeptide, and possess pharmacokinetic characteristics that confirm the drug-likeness of these compounds. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 17460441 1746045X |
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| DOI: | 10.1080/17460441.2017.1287171 |