Antiviral activity of broad-spectrum and enterovirus-specific inhibitors against clinical isolates of enterovirus D68

Sun, Liang; Meijer, Adam; Froeyen, Mathy; Zhang, Linlin; Thibaut, Hendrik Jan; Baggen, Jim; George, Shyla; Vernachio, John; van Kuppeveld, Frank JM; Leyssen, Pieter; Hilgenfeld, Rolf; Neyts, Johan; Delang, Leen

doi:10.1128/AAC.01375-15

Antiviral activity of broad-spectrum and enterovirus-specific inhibitors against clinical isolates of enterovirus D68

Author:

Sun, Liang

Meijer, Adam ; Froeyen, Mathy ; Zhang, Linlin ; Thibaut, Hendrik Jan ; Baggen, Jim ; George, Shyla ; Vernachio, John ; van Kuppeveld, Frank JM ; Leyssen, Pieter ; Hilgenfeld, Rolf ; Neyts, Johan ; Delang, Leen

Keywords:

Science & Technology, Life Sciences & Biomedicine, Microbiology, Pharmacology & Pharmacy, FAVIPIRAVIR T-705, 3C PROTEASE, CHILDREN, VIRUS, REPLICATION, RUPINTRIVIR, PLECONARIL, RESISTANCE, EMERGENCE, INFECTION, Antiviral Agents, Drug Resistance, Viral, Enterovirus D, Human, Enterovirus Infections, Humans, Microbial Sensitivity Tests, Models, Molecular, Oxadiazoles, Oxazoles, Receptors, Drug, Respiratory Tract Infections, Viral Proteins, Virus Replication, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology and Pharmaceutical Sciences, 3107 Microbiology, 3207 Medical microbiology, 3214 Pharmacology and pharmaceutical sciences

Abstract:

We investigated the susceptibility of 10 enterovirus D68 (EV-D68) isolates (belonging to clusters A, B, and C) to (entero)virus inhibitors with different mechanisms of action. The 3C-protease inhibitors proved to be more efficient than enviroxime and pleconaril, which in turn were more effective than vapendavir and pirodavir. Favipiravir proved to be a weak inhibitor. Resistance to pleconaril maps to V69A in the VP1 protein, and resistance to rupintrivir maps to V104I in the 3C protease. A structural explanation of why both substitutions may cause resistance is provided.