High throughput profiling identified PA-L106R amino acid substitution in A(H1N1)pdm09 influenza virus that confers reduced susceptibility to baloxavir in vitro

• Published in: Antiviral research Vol. 229; p. 105961
• Main Authors: Chen, Dongdong, Su, Wen, Choy, Ka-Tim, Chu, Yan Sing, Lin, Chi Ho, Yen, Hui-Ling
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2024
• Subjects: Amino Acid Substitution; Animals; Antiviral Agents - pharmacology; Baloxavir; Cap-dependent endonuclease inhibitor; Deep mutational scanning; Dibenzothiepins - pharmacology; Dogs; Drug Resistance, Viral - genetics; Fitness; High-Throughput Nucleotide Sequencing; Humans; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - genetics; Influenza virus; Influenza, Human - drug therapy; Influenza, Human - virology; Madin Darby Canine Kidney Cells; Morpholines - pharmacology; Oxazines - pharmacology; Pyridones - pharmacology; Reduced susceptibility; RNA-Dependent RNA Polymerase - genetics; Thiepins - pharmacology; Triazines - pharmacology; Viral Proteins - genetics; Virus Replication - drug effects; Reduced susceptibility; Cap-dependent endonuclease inhibitor; Deep mutational scanning; Influenza virus; Baloxavir; Fitness

Baloxavir acid (BXA) is a pan-influenza antiviral that targets the cap-dependent endonuclease of the polymerase acidic (PA) protein required for viral mRNA synthesis. To gain a comprehensive understanding on the molecular changes associated with reduced susceptibility to BXA and their fitness profil...