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Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2

Hirofumi Ohashi, Takayuki Hishiki, Daisuke Akazawa, Kwang Su Kim, Joohyeon Woo, Kaho Shionoya, Kana Tsuchimoto, Shoya Iwanami, Saya Moriyama, Hitomi Kinoshita, Souichi Yamada, Yudai Kuroda, Tsukasa Yamamoto, Noriko Kishida, Shinji Watanabe, Hideki Hasegawa, Hideki Ebihara, Tadaki Suzuki, Ken Maeda, Shuetsu Fukushi, Yoshimasa Takahashi, Shingo Iwami, Koichi Watashi
doi: https://doi.org/10.1101/2022.02.27.482147
Hirofumi Ohashi
1Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Takayuki Hishiki
1Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Daisuke Akazawa
1Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Kwang Su Kim
2Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan
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Joohyeon Woo
2Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan
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Kaho Shionoya
3Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
4Department of Applied Biological Science, Tokyo University of Science, Noda 278-8510, Japan
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Kana Tsuchimoto
1Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Shoya Iwanami
2Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan
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Saya Moriyama
1Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Hitomi Kinoshita
5Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Souichi Yamada
5Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Yudai Kuroda
6Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Tsukasa Yamamoto
6Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Noriko Kishida
7Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases; Tokyo 208-0011, Japan
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Shinji Watanabe
7Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases; Tokyo 208-0011, Japan
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Hideki Hasegawa
7Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases; Tokyo 208-0011, Japan
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Hideki Ebihara
5Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Tadaki Suzuki
8Department of Pathology, National Institute of Infectious Diseases; Tokyo, 162-8640, Japan
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Ken Maeda
6Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Shuetsu Fukushi
5Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Yoshimasa Takahashi
1Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
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Shingo Iwami
2Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan
9Institute of Mathematics for Industry, Kyushu University, Fukuoka, Japan
10Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
11Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS), RIKEN, Saitama, Japan
12NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan
13Science Groove Inc., Fukuoka, Japan 8100041
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  • For correspondence: iwami.iblab@bio.nagoya-u.ac.jp kwatashi@niid.go.jp
Koichi Watashi
1Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
3Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
4Department of Applied Biological Science, Tokyo University of Science, Noda 278-8510, Japan
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  • For correspondence: iwami.iblab@bio.nagoya-u.ac.jp kwatashi@niid.go.jp
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Summary

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 has spread in many countries, replacing the earlier Omicron subvariant BA.1 and other variants. Here, using a cell culture infection assay, we quantified the intrinsic sensitivity of BA.2 and BA.1 compared with other variants of concern, Alpha, Gamma, and Delta, to five approved-neutralizing antibodies and antiviral drugs. Our assay revealed the diverse sensitivities of these variants to antibodies, including the loss of response of both BA.1 and BA.2 to casirivimab and of BA.1 to imdevimab. In contrast, EIDD-1931 and nirmatrelvir showed a more conserved activities to these variants. The viral response profile combined with mathematical analysis estimated differences in antiviral effects among variants in the clinical concentrations. These analyses provide essential evidence that gives insight into variant emergence’s impact on choosing optimal drug treatment.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 28, 2022.
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Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2
Hirofumi Ohashi, Takayuki Hishiki, Daisuke Akazawa, Kwang Su Kim, Joohyeon Woo, Kaho Shionoya, Kana Tsuchimoto, Shoya Iwanami, Saya Moriyama, Hitomi Kinoshita, Souichi Yamada, Yudai Kuroda, Tsukasa Yamamoto, Noriko Kishida, Shinji Watanabe, Hideki Hasegawa, Hideki Ebihara, Tadaki Suzuki, Ken Maeda, Shuetsu Fukushi, Yoshimasa Takahashi, Shingo Iwami, Koichi Watashi
bioRxiv 2022.02.27.482147; doi: https://doi.org/10.1101/2022.02.27.482147
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Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2
Hirofumi Ohashi, Takayuki Hishiki, Daisuke Akazawa, Kwang Su Kim, Joohyeon Woo, Kaho Shionoya, Kana Tsuchimoto, Shoya Iwanami, Saya Moriyama, Hitomi Kinoshita, Souichi Yamada, Yudai Kuroda, Tsukasa Yamamoto, Noriko Kishida, Shinji Watanabe, Hideki Hasegawa, Hideki Ebihara, Tadaki Suzuki, Ken Maeda, Shuetsu Fukushi, Yoshimasa Takahashi, Shingo Iwami, Koichi Watashi
bioRxiv 2022.02.27.482147; doi: https://doi.org/10.1101/2022.02.27.482147

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