The enterovirus 3C protease inhibitor SG85 efficiently blocks rhinovirus replication and is not cross-resistant with rupintrivir

Céline Lacroix; Shyla George; Pieter Leyssen; Rolf Hilgenfeld; Johan Neyts

doi:10.1128/AAC.00534-15

The enterovirus 3C protease inhibitor SG85 efficiently blocks rhinovirus replication and is not cross-resistant with rupintrivir

Céline Lacroix, Shyla George, Pieter Leyssen, Rolf Hilgenfeld, Johan Neyts^*

^*Corresponding author for this work

KU Leuven

23 Citations (Scopus)

Abstract

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 μM). 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.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Volume	59
Issue number	9
Pages (from-to)	5814-5818
Number of pages	5
ISSN	0066-4804
DOIs	https://doi.org/10.1128/AAC.00534-15
Publication status	Published - 01.09.2015

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abstract = "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 μM). 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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AU - Lacroix, Céline

AU - George, Shyla

AU - Leyssen, Pieter

AU - Hilgenfeld, Rolf

AU - Neyts, Johan

PY - 2015/9/1

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N2 - 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 μM). 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.

AB - 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 μM). 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.

UR - https://www.scopus.com/pages/publications/84940944425

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The enterovirus 3C protease inhibitor SG85 efficiently blocks rhinovirus replication and is not cross-resistant with rupintrivir

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