Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 59, Issue 9, Pages 5814-5818Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00534-15
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Funding
- Agency for Innovation by Science and Technology (IWT, Belgium)
- European Commission through its SILVER project [HEALTH-F3-2010-260644]
- KU Leuven Geconcerteerde Onderzoeksactie [GOA 10/014]
- BELSPO IUAP consortium BELVIR (Belgium)
- German Center for Infection Research (DZIF) [TTU 01.803]
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The novel enterovirus protease inhibitor (PI) SG85 effectively inhibits the in vitro replication of 14 rhinoviruses representative of species A and B (median 50% effective concentration, 0.04 mu M). A low-level SG85-resistant variant was selected that carried amino acid substitutions S127G and T143A in the 3C protease. Both substitutions are required for low-level resistance to SG85, as demonstrated by reverse genetics. Interestingly, there is no cross-resistance to SG85 and rupintrivir (another PI); a structural explanation is provided for this observation.
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