ABCMdb

PMID: 26522770

Kelly JT, De Colibus L, Elliott L, Fry EE, Stuart DI, Rowlands DJ, Stonehouse NJ
Potent antiviral agents fail to elicit genetically-stable resistance mutations in either enterovirus 71 or Coxsackievirus A16.
Antiviral Res. 2015 Dec;124:77-82. doi: 10.1016/j.antiviral.2015.10.006. Epub 2015 Oct 30., [PubMed]

Sentences

No. Mutations Sentence Comment

26 ABCD1 p.Val123Ile Sequencing revealed three different VP1 mutants in EV71 (I113L, I113M, I113M/V123I) and one in CVA16 (L113F) (Table 1). Login to comment 27 ABCD1 p.Val123Ile Virus passaged in a combination of NLD/ GPP3 over 30 passages maintained the I113M/V123I mutations (n &#bc; 1). Login to comment 30 ABCD1 p.Val123Ile Mutations I113M and V123I are located on the inside of the VP1 pocket and I113 is one of the residues involved in compound binding (Fig. 2B). Login to comment 35 ABCD1 p.Val123Ile The difference in the lowest free energy of folding (DDGfolding) between the WT and EV71 I113M or V123I mutants was &#fe;0.73 and &#fe; 0.98 kcal/mol, respectively. Login to comment 37 ABCD1 p.Val123Ile The mutations I113M and V123I appeared to cause a shrinking of the VP1 pocket, with the methionine residue pointing inside, suggesting a steric clash with the Fig. 1. Login to comment 52 ABCD1 p.Val123Ile ABCD1 p.Val123Ile ABCD1 p.Val123Ile ABCD1 p.Val123Ile Virus/Compound Mutation(s) Number sequenced EV71/NLD I113M (62%), I113L (31%), I113M/V123I (7%) n &#bc; 13 EV71/GPP3 I113M/V123I n &#bc; 4 EV71/ALD I113M/V123I n &#bc; 1 EV71/NLD &#fe; GPP3 I113M/V123I n &#bc; 12 CVA16/GPP3 L113F n &#bc; 10 Fig. 2. Login to comment 62 ABCD1 p.Val123Ile The two mutated side chains I113M and V123I are shown as grey balls-and-sticks. Login to comment 73 ABCD1 p.Val123Ile These data suggest that the I113M/V123I mutation prevented compound binding as the thermostability of the resistant isolates was not increased in the presence of NLD. Login to comment 74 ABCD1 p.Val123Ile The bulkier side chains of the I113M and L113F mutations are predicted to point directly into the pocket, reducing the space available for inhibitor binding and the V123I mutation reduces this further. Login to comment