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Volume 31, Number 4—April 2025
Research

Antiviral Susceptibility of Influenza A(H5N1) Clade 2.3.2.1c and 2.3.4.4b Viruses from Humans, 2023–2024

Philippe Noriel Q. Pascua1, Anton Chesnokov1, Ha T. Nguyen, Han Di, Juan De La Cruz, Yunho Jang, Andrei A. Ivashchenko, Alexandre V. Ivachtchenko, Erik A. Karlsson, Borann Sar, Chin Savuth, Timothy M. Uyeki, Charles Todd Davis, and Larisa V. GubarevaComments to Author 
Author affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (P.N.Q. Pascua, A. Chesnokov, H.T. Nguyen, H. Di, J.D.L. Cruz, Y. Jang, T.M. Uyeki, C.T. Davis, L.V. Gubareva); ChemDiv, San Diego, California, USA (A.A. Ivashchenko, A.V. Ivachtchenko); Avisa LLC, Hallandale Beach, Florida, USA (A.V. Ivachtchenko); Virology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia (E.A. Karlsson); US Centers for Disease Control and Prevention Country Office, Phnom Penh (B. Sar); National Institute of Public Health, Ministry of Health, Phnom Penh (C. Savuth)

Main Article

Table 4

Susceptibility of HPAI A(H5N1) viruses isolated from humans to polymerase inhibitors in cell culture-based assay IRINA, 2023–2024*

Influenza A(H5N1) virus Mean EC50, nM
PA-CEN inhibitor
 PB2 inhibitor
Baloxavir (fold change) Tivoxavir (fold change) Pimodivir (fold change)
Clade 2.3.2.1c, median EC50, n = 7 0.55 0.52 0.40
  A/Cambodia/NPH230032/2023 0.56 ± 0.20 0.84 ± 0.23 0.06 ± 0.01
  A/Cambodia/2302009/2023 0.74 ± 0.25 0.43 ± 0.18 0.07 ± 0.02
  A/Cambodia/NPH230776/2023 0.54 ± 0.08 0.56 ± 0.22 0.37 ± 0.10
  A/Cambodia/KSH230332/2023 0.55 ± 0.12 0.52 ± 0.13 0.34 ± 0.14
  A/Cambodia/2311257/2023 0.62 ± 0.12 0.54 ± 0.17 0.40 ± 0.09
  A/Cambodia/24020155/2024 0.54 ± 0.16 0.52 ± 0.14 0.91 ± 0.31
  A/Cambodia/24020179/2024
 0.40 ± 0.14
 0.47 ± 0.12
0.45 ± 0.06
Clade 2.3.4.4b, median EC50, n = 7 0.83 0.88 1.32
  A/Chile/25945/2023 0.96 ± 0.28 1.07 ± 0.17 0.73 ± 0.18
  A/Texas/37/2024 1.06 ± 0.22 1.09 ± 0.09 1.66 ± 0.17
  A/Michigan/90/2024 0.57 ± 0.21 0.56 ± 0.22 1.48 ± 0.65
  A/Colorado/109/2024 0.44 ± 0.35 0.72 ± 0.30 1.32 ± 0.46
  A/Colorado/137/2024 0.95 ± 0.30 0.98 ± 0.24 1.51 ± 0.27
  A/Colorado/139/2024 0.70 ± 0.07 0.77 ± 0.19 1.19 ± 0.12
  A/California/134/2024
 0.73 ± 0.12
 0.47 ± 0.07
1.03 ± 0.30
Control viruses†
  A/bald eagle/FL/2022 (H5N1)‡ 0.42 ± 0.20 0.76 ± 0.29 0.46 ± 0.19
  A/Illinois/08/2018 (H1N1)pdm09 1.16 ± 0.24 1.46 ± 0.32 0.93 ± 0.22
  A/Illinois/08/2018 (H1N1)pdm09, PA-I38T 137.05 ± 17.43 (116) 72.86 ± 11.00 (50) 0.49 ± 0.14
  A/New Jersey/24/2017 (H3N2) 0.72 ± 0.14 0.57 ± 0.26 0.60 ± 0.25
  A/Pennsylvania/242/2017 (H3N2), PB2-S342R 0.35 ± 0.10 0.29 ± 0.11 99.50 ± 27.26 (166)

*Data shown are means +SDs of >3 experiments. Fold change was calculated from sequence-matched control virus. EC50, 50% effective concentration; HPAI, highly pathogenic avian influenza; IRINA, influenza replication inhibition neuraminidase-based assay; PA-CEN, PA cap-dependent endonuclease. †Control seasonal viruses were from Centers for Disease Control and Prevention Baloxavir Susceptibility Reference Virus Panel (no. FR-1678 ver1.1) and virus inventory. ‡Clade 2.3.4.4b A(H5N1) virus, A/bald eagle/Florida/W22–134-OP/2022 (GISAID ID no. EPI_ISL_15063846), was used as a control.

Main Article

1These first authors contributed equally to this article.

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