Abstract：
:The development of drug resistance has long plagued our efforts to curtail viral infections in general and influenza in particular. The problem is particularly challenging since the exact mode of resistance may be difficult to predict, without waiting for untreatable strains to evolve. Herein, a different approach is taken. Using a novel genetic screen, we map the resistance options of influenza's M2 channel against its aminoadamantane antiviral inhibitors. In the process, we could identify clinically known resistant mutations in a completely unbiased manner. Additionally, novel mutations were obtained, which, while known to exist in circulating viruses, were not previously classified as drug resistant. Finally, we demonstrated the approach against an anti-influenza drug that has not seen clinical use, identifying several resistance mutations in the process. In conclusion, we present and employ a method to predict the resistance options of influenza's M2 channel to antiviral agents ahead of clinical use and without medical hazard.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Assa D,Alhadeff R,Krugliak M,Arkin ITdoi
10.1016/j.jmb.2016.08.007subject
Has Abstractpub_date
2016-10-09 00:00:00pages
4209-4217issue
20eissn
0022-2836issn
1089-8638pii
S0022-2836(16)30302-3journal_volume
428pub_type
杂志文章abstract：:Allostery in a protein involves effector binding at an allosteric site that changes the structure and/or dynamics at a distant, functional site. In addition to the chemical equilibrium of ligand binding, allostery involves a conformational equilibrium between one protein substate that binds the effector and a second s...
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pub_type： 杂志文章
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journal_title：Journal of molecular biology
pub_type： 杂志文章
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journal_title：Journal of molecular biology
pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：1998-10-02 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.jmb.2009.10.062
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.02.009
更新日期：2006-04-28 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(90)90143-A
更新日期：1990-07-05 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.2660
更新日期：1999-04-23 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1995.0371
更新日期：1995-07-07 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
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journal_title：Journal of molecular biology
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journal_title：Journal of molecular biology
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1460
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abstract：:The pentameric ATPase motor gp16 packages double-stranded DNA into the bacteriophage phi29 virus capsid. On the basis of the results of single-molecule experimental studies, we propose a push and roll mechanism to explain how the packaging motor translocates the DNA in bursts of four 2.5 bp power strokes, while rotati...
journal_title：Journal of molecular biology
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