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. 2023 Jul 4;14:3952. doi: 10.1038/s41467-023-39704-x

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — Wild-type virus and Nsp5-L50F/E166V (left) or Nsp5-L50F/E166A/L167F (right) were mixed at a ratio of 3:7 based on their virus titers, and the virus mixture was intranasally inoculated into hamsters (n = 10 per group). Hamsters were treated with nirmatrelvir (n = 5, lower panels) or left untreated (n = 5, upper panels). Nasal turbinates and lungs were collected from the infected animals at 4 dpi and the frequency of each virus was determined by deep sequence analysis. The frequency of wild-type virus in the treated hamsters was compared with that in the untreated animals by using the Mann–Whitney test (two-sided) followed by the two-stage step-up procedure of the Benjamini, Krieger, and Yekutieli test. The frequency of wild-type virus in the nasal turbinate and lungs of treated hamsters was significantly decreased in co-infection experiments with Nsp5-L50F/E166V (p = 0.00794 and p = 0.00794) or Nsp5-L50F/E166A/L167F (p = 0.00794 and p = 0.0476), respectively.