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2. Virological characteristics of a SARS-CoV-2-related bat coronavirus, BANAL-20-236

Author

Sawa, Hirofumi, Mizuma, Keita, Li, Jingshu, Mimura, Yume, Ohari, Yuma, Tsubo, Tomoya, Ferdous, Zannatul, Shishido, Kenji, Mohri, Hiromi, Iida, Miki, Tsujino, Shuhei, Misawa, Naoko, Usui, Kaoru, Saikruang, Wilaiporn, Lytras, Spyridon, Kawakubo, Shusuke, Nishumura, Luca, Mendoza Tolentino, Jarel Elgin, Li, Wenye, Yo, Maximilian Stanley, Horinaka, Kio, Suganami, Mai, Chiba, Mika, Yoshimura, Ryo, Yasuda, Kyoko, Iida, Keiko, Strange, Adam Patrick, Ohsumi, Naomi, Tanaka, Shiho, Ogawa, Eiko, Okumura, Kaho, Fukuda, Tsuki, Osujo, Rina, Yoshida, Isao, Nakagawa, So, Takaori-Kondo, Akifumi, Shirakawa, Kotaro, Nagata, Kayoko, Nomura, Ryosuke, Horisawa, Yoshihito, Tashiro, Yusuke, Kawai, Yugo, Nakata, Yoshitaka, Futatsusako, Hiroki, Sakamoto, Ayaka, Yasuhara, Naoko, Hashiguchi, Takao, Suzuki, Tateki, Kimura, Kanako, Sasaki, Jiei, Nakajima, Yukari, Yajima, Hisano, Irie, Takashi, Kawabata, Ryoko, Sasaki-Tabata, Kaori, Shimizu, Ryo, Monira Begum, M.S.T., Jonathan, Michael, Mugita, Yuka, Leong, Sharee, Takahashi, Otowa, Ichihara, Kimiko, Ueno, Takamasa, Motozono, Chihiro, Toyoda, Mako, Saito, Akatsuki, Kosaka, Anon, Kawano, Miki, Matsubara, Natsumi, Nishiuchi, Tomoko, Zahradnik, Jiri, Andrikopoulos, Prokopios, Padilla-Blanco, Miguel, Konar, Aditi, Fujita, Shigeru, Plianchaisuk, Arnon, Deguchi, Sayaka, Ito, Hayato, Nao, Naganori, Wang, Lei, Nasser, Hesham, Tamura, Tomokazu, Kimura, Izumi, Kashima, Yukie, Suzuki, Rigel, Suzuki, Saori, Kida, Izumi, Tsuda, Masumi, Oda, Yoshitaka, Hashimoto, Rina, Watanabe, Yukio, Uriu, Keiya, Yamasoba, Daichi, Guo, Ziyi, Hinay, Alfredo A., Jr., Kosugi, Yusuke, Chen, Luo, Pan, Lin, Kaku, Yu, Chu, Hin, Donati, Flora, Temmam, Sarah, Eloit, Marc, Yamamoto, Yuki, Nagamoto, Tetsuharu, Asakura, Hiroyuki, Nagashima, Mami, Sadamasu, Kenji, Yoshimura, Kazuhisa, Suzuki, Yutaka, Ito, Jumpei, Ikeda, Terumasa, Tanaka, Shinya, Matsuno, Keita, Fukuhara, Takasuke, Takayama, Kazuo, and Sato, Kei

Published
2024
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4. Virological characteristics of a SARS-CoV-2-related bat coronavirus, BANAL-20-236

Author

Fujita, Shigeru, primary, Plianchaisuk, Arnon, additional, Deguchi, Sayaka, additional, Ito, Hayato, additional, Nao, Naganori, additional, Wang, Lei, additional, Nasser, Hesham, additional, Tamura, Tomokazu, additional, Kimura, Izumi, additional, Kashima, Yukie, additional, Suzuki, Rigel, additional, Suzuki, Saori, additional, Kida, Izumi, additional, Tsuda, Masumi, additional, Oda, Yoshitaka, additional, Hashimoto, Rina, additional, Watanabe, Yukio, additional, Uriu, Keiya, additional, Yamasoba, Daichi, additional, Guo, Ziyi, additional, Hinay, Alfredo A., additional, Kosugi, Yusuke, additional, Chen, Luo, additional, Pan, Lin, additional, Kaku, Yu, additional, Chu, Hin, additional, Donati, Flora, additional, Temmam, Sarah, additional, Eloit, Marc, additional, Yamamoto, Yuki, additional, Nagamoto, Tetsuharu, additional, Asakura, Hiroyuki, additional, Nagashima, Mami, additional, Sadamasu, Kenji, additional, Yoshimura, Kazuhisa, additional, Suzuki, Yutaka, additional, Sawa, Hirofumi, additional, Mizuma, Keita, additional, Li, Jingshu, additional, Mimura, Yume, additional, Ohari, Yuma, additional, Tsubo, Tomoya, additional, Ferdous, Zannatul, additional, Shishido, Kenji, additional, Mohri, Hiromi, additional, Iida, Miki, additional, Tsujino, Shuhei, additional, Misawa, Naoko, additional, Usui, Kaoru, additional, Saikruang, Wilaiporn, additional, Lytras, Spyridon, additional, Kawakubo, Shusuke, additional, Nishumura, Luca, additional, Mendoza Tolentino, Jarel Elgin, additional, Li, Wenye, additional, Yo, Maximilian Stanley, additional, Horinaka, Kio, additional, Suganami, Mai, additional, Chiba, Mika, additional, Yoshimura, Ryo, additional, Yasuda, Kyoko, additional, Iida, Keiko, additional, Strange, Adam Patrick, additional, Ohsumi, Naomi, additional, Tanaka, Shiho, additional, Ogawa, Eiko, additional, Okumura, Kaho, additional, Fukuda, Tsuki, additional, Osujo, Rina, additional, Yoshida, Isao, additional, Nakagawa, So, additional, Takaori-Kondo, Akifumi, additional, Shirakawa, Kotaro, additional, Nagata, Kayoko, additional, Nomura, Ryosuke, additional, Horisawa, Yoshihito, additional, Tashiro, Yusuke, additional, Kawai, Yugo, additional, Nakata, Yoshitaka, additional, Futatsusako, Hiroki, additional, Sakamoto, Ayaka, additional, Yasuhara, Naoko, additional, Hashiguchi, Takao, additional, Suzuki, Tateki, additional, Kimura, Kanako, additional, Sasaki, Jiei, additional, Nakajima, Yukari, additional, Yajima, Hisano, additional, Irie, Takashi, additional, Kawabata, Ryoko, additional, Sasaki-Tabata, Kaori, additional, Shimizu, Ryo, additional, Monira Begum, M.S.T., additional, Jonathan, Michael, additional, Mugita, Yuka, additional, Leong, Sharee, additional, Takahashi, Otowa, additional, Ichihara, Kimiko, additional, Ueno, Takamasa, additional, Motozono, Chihiro, additional, Toyoda, Mako, additional, Saito, Akatsuki, additional, Kosaka, Anon, additional, Kawano, Miki, additional, Matsubara, Natsumi, additional, Nishiuchi, Tomoko, additional, Zahradnik, Jiri, additional, Andrikopoulos, Prokopios, additional, Padilla-Blanco, Miguel, additional, Konar, Aditi, additional, Ito, Jumpei, additional, Ikeda, Terumasa, additional, Tanaka, Shinya, additional, Matsuno, Keita, additional, Fukuhara, Takasuke, additional, Takayama, Kazuo, additional, and Sato, Kei, additional

Published
2024
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6. Cell response analysis in SARS-CoV-2 infected bronchial organoids

Author

Sano, Emi, Suzuki, Tatsuya, Hashimoto, Rina, Itoh, Yumi, Sakamoto, Ayaka, Sakai, Yusuke, Saito, Akatsuki, Okuzaki, Daisuke, Motooka, Daisuke, Muramoto, Yukiko, Noda, Takeshi, Takasaki, Tomohiko, Sakuragi, Jun-Ichi, Minami, Shohei, Kobayashi, Takeshi, Yamamoto, Takuya, Matsumura, Yasufumi, Nagao, Miki, Okamoto, Toru, and Takayama, Kazuo

Published
2022
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10. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020)

Author

Egi, Moritoki, Ogura, Hiroshi, Yatabe, Tomoaki, Atagi, Kazuaki, Inoue, Shigeaki, Iba, Toshiaki, Kakihana, Yasuyuki, Kawasaki, Tatsuya, Kushimoto, Shigeki, Kuroda, Yasuhiro, Kotani, Joji, Shime, Nobuaki, Taniguchi, Takumi, Tsuruta, Ryosuke, Doi, Kent, Doi, Matsuyuki, Nakada, Taka-aki, Nakane, Masaki, Fujishima, Seitaro, Hosokawa, Naoto, Masuda, Yoshiki, Matsushima, Asako, Matsuda, Naoyuki, Yamakawa, Kazuma, Hara, Yoshitaka, Sakuraya, Masaaki, Ohshimo, Shinichiro, Aoki, Yoshitaka, Inada, Mai, Umemura, Yutaka, Kawai, Yusuke, Kondo, Yutaka, Saito, Hiroki, Taito, Shunsuke, Takeda, Chikashi, Terayama, Takero, Tohira, Hideo, Hashimoto, Hideki, Hayashida, Kei, Hifumi, Toru, Hirose, Tomoya, Fukuda, Tatsuma, Fujii, Tomoko, Miura, Shinya, Yasuda, Hideto, Abe, Toshikazu, Andoh, Kohkichi, Iida, Yuki, Ishihara, Tadashi, Ide, Kentaro, Ito, Kenta, Ito, Yusuke, Inata, Yu, Utsunomiya, Akemi, Unoki, Takeshi, Endo, Koji, Ouchi, Akira, Ozaki, Masayuki, Ono, Satoshi, Katsura, Morihiro, Kawaguchi, Atsushi, Kawamura, Yusuke, Kudo, Daisuke, Kubo, Kenji, Kurahashi, Kiyoyasu, Sakuramoto, Hideaki, Shimoyama, Akira, Suzuki, Takeshi, Sekine, Shusuke, Sekino, Motohiro, Takahashi, Nozomi, Takahashi, Sei, Takahashi, Hiroshi, Tagami, Takashi, Tajima, Goro, Tatsumi, Hiroomi, Tani, Masanori, Tsuchiya, Asuka, Tsutsumi, Yusuke, Naito, Takaki, Nagae, Masaharu, Nagasawa, Ichiro, Nakamura, Kensuke, Nishimura, Tetsuro, Nunomiya, Shin, Norisue, Yasuhiro, Hashimoto, Satoru, Hasegawa, Daisuke, Hatakeyama, Junji, Hara, Naoki, Higashibeppu, Naoki, Furushima, Nana, Furusono, Hirotaka, Matsuishi, Yujiro, Matsuyama, Tasuku, Minematsu, Yusuke, Miyashita, Ryoichi, Miyatake, Yuji, Moriyasu, Megumi, Yamada, Toru, Yamada, Hiroyuki, Yamamoto, Ryo, Yoshida, Takeshi, Yoshida, Yuhei, Yoshimura, Jumpei, Yotsumoto, Ryuichi, Yonekura, Hiroshi, Wada, Takeshi, Watanabe, Eizo, Aoki, Makoto, Asai, Hideki, Abe, Takakuni, Igarashi, Yutaka, Iguchi, Naoya, Ishikawa, Masami, Ishimaru, Go, Isokawa, Shutaro, Itakura, Ryuta, Imahase, Hisashi, Imura, Haruki, Irinoda, Takashi, Uehara, Kenji, Ushio, Noritaka, Umegaki, Takeshi, Egawa, Yuko, Enomoto, Yuki, Ota, Kohei, Ohchi, Yoshifumi, Ohno, Takanori, Ohbe, Hiroyuki, Oka, Kazuyuki, Okada, Nobunaga, Okada, Yohei, Okano, Hiromu, Okamoto, Jun, Okuda, Hiroshi, Ogura, Takayuki, Onodera, Yu, Oyama, Yuhta, Kainuma, Motoshi, Kako, Eisuke, Kashiura, Masahiro, Kato, Hiromi, Kanaya, Akihiro, Kaneko, Tadashi, Kanehata, Keita, Kano, Ken-ichi, Kawano, Hiroyuki, Kikutani, Kazuya, Kikuchi, Hitoshi, Kido, Takahiro, Kimura, Sho, Koami, Hiroyuki, Kobashi, Daisuke, Saiki, Iwao, Sakai, Masahito, Sakamoto, Ayaka, Sato, Tetsuya, Shiga, Yasuhiro, Shimoto, Manabu, Shimoyama, Shinya, Shoko, Tomohisa, Sugawara, Yoh, Sugita, Atsunori, Suzuki, Satoshi, Suzuki, Yuji, Suhara, Tomohiro, Sonota, Kenji, Takauji, Shuhei, Takashima, Kohei, Takahashi, Sho, Takahashi, Yoko, Takeshita, Jun, Tanaka, Yuuki, Tampo, Akihito, Tsunoyama, Taichiro, Tetsuhara, Kenichi, Tokunaga, Kentaro, Tomioka, Yoshihiro, Tomita, Kentaro, Tominaga, Naoki, Toyosaki, Mitsunobu, Toyoda, Yukitoshi, Naito, Hiromichi, Nagata, Isao, Nagato, Tadashi, Nakamura, Yoshimi, Nakamori, Yuki, Nahara, Isao, Naraba, Hiromu, Narita, Chihiro, Nishioka, Norihiro, Nishimura, Tomoya, Nishiyama, Kei, Nomura, Tomohisa, Haga, Taiki, Hagiwara, Yoshihiro, Hashimoto, Katsuhiko, Hatachi, Takeshi, Hamasaki, Toshiaki, Hayashi, Takuya, Hayashi, Minoru, Hayamizu, Atsuki, Haraguchi, Go, Hirano, Yohei, Fujii, Ryo, Fujita, Motoki, Fujimura, Naoyuki, Funakoshi, Hiraku, Horiguchi, Masahito, Maki, Jun, Masunaga, Naohisa, Matsumura, Yosuke, Mayumi, Takuya, Minami, Keisuke, Miyazaki, Yuya, Miyamoto, Kazuyuki, Murata, Teppei, Yanai, Machi, Yano, Takao, Yamada, Kohei, Yamada, Naoki, Yamamoto, Tomonori, Yoshihiro, Shodai, Tanaka, Hiroshi, and Nishida, Osamu

Published
2021
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14. Virological characterization of the 2022 outbreak-causing monkeypox virus using human keratinocytes and colon organoids

Author

Watanabe, Yukio, Kimura, Izumi, Hashimoto, Rina, Sakamoto, Ayaka, Yasuhara, Naoko, Yamamoto, Takuya, Genotype to Phenotype Japan (GP-Japan) Consortium, Sato, Kei, and Takayama, Kazuo

Subjects
keratinocytes, colon organoids, Congo Basin clade (clade I), monkeypox virus, West African clade (clade IIa), 2022 MPXV (clade IIb)
Abstract

The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future., ヒトiPS細胞由来大腸オルガノイドおよびヒトケラチノサイトを用いたmpoxウイルス2022年株の解析. 京都大学プレスリリース. 2023-06-07.

Published
2023

15. Evaluation of Broad Anti-Coronavirus Activity of Autophagy-Related Compounds Using Human Airway Organoids

Author

Hashimoto, Rina, primary, Tamura, Tomokazu, additional, Watanabe, Yukio, additional, Sakamoto, Ayaka, additional, Yasuhara, Naoko, additional, Ito, Hayato, additional, Nakano, Masahiro, additional, Fuse, Hiromitsu, additional, Ohta, Akira, additional, Noda, Takeshi, additional, Matsumura, Yasufumi, additional, Nagao, Miki, additional, Yamamoto, Takuya, additional, Fukuhara, Takasuke, additional, and Takayama, Kazuo, additional

Published
2023
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18. Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips

Author

Deguchi, Sayaka, primary, Kosugi, Kaori, additional, Hashimoto, Rina, additional, Sakamoto, Ayaka, additional, Yamamoto, Masaki, additional, Krol, Rafal P, additional, Gee, Peter, additional, Negoro, Ryosuke, additional, Noda, Takeshi, additional, Yamamoto, Takuya, additional, Torisawa, Yu-suke, additional, Nagao, Miki, additional, and Takayama, Kazuo, additional

Published
2023
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19. Virological characterization of the 2022 outbreak-causing monkeypox virus using human keratinocytes and colon organoids

Author

60546993, 10759509, Watanabe, Yukio, Kimura, Izumi, Hashimoto, Rina, Sakamoto, Ayaka, Yasuhara, Naoko, Yamamoto, Takuya, Genotype to Phenotype Japan (GP-Japan) Consortium, Sato, Kei, Takayama, Kazuo, 60546993, 10759509, Watanabe, Yukio, Kimura, Izumi, Hashimoto, Rina, Sakamoto, Ayaka, Yasuhara, Naoko, Yamamoto, Takuya, Genotype to Phenotype Japan (GP-Japan) Consortium, Sato, Kei, and Takayama, Kazuo

Abstract

The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future.

Published
2023

20. Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips

Author

00422410, 60546993, 80523993, 10759509, Deguchi, Sayaka, Kosugi, Kaori, Hashimoto, Rina, Sakamoto, Ayaka, Yamamoto, Masaki, Krol, Rafal P, Gee, Peter, Negoro, Ryosuke, Noda, Takeshi, Yamamoto, Takuya, Torisawa, Yu-suke, Nagao, Miki, Takayama, Kazuo, 00422410, 60546993, 80523993, 10759509, Deguchi, Sayaka, Kosugi, Kaori, Hashimoto, Rina, Sakamoto, Ayaka, Yamamoto, Masaki, Krol, Rafal P, Gee, Peter, Negoro, Ryosuke, Noda, Takeshi, Yamamoto, Takuya, Torisawa, Yu-suke, Nagao, Miki, and Takayama, Kazuo

Abstract

SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses. First, we developed liver-on-a-chip (LoC) which recapitulating hepatic functions around the intrahepatic bile duct and blood vessel. We found that hepatic dysfunctions, but not hepatobiliary diseases, were strongly induced by SARS-CoV-2 infection. Next, we evaluated the therapeutic effects of COVID-19 drugs to inhibit viral replication and recover hepatic dysfunctions, and found that the combination of anti-viral and immunosuppressive drugs (Remdesivir and Baricitinib) is effective to treat hepatic dysfunctions caused by SARS-CoV-2 infection. Finally, we analyzed the sera obtained from COVID-19 patients, and revealed that COVID-19 patients, who were positive for serum viral RNA, are likely to become severe and develop hepatic dysfunctions, as compared with COVID-19 patients who were negative for serum viral RNA. We succeeded in modeling the liver pathophysiology of COVID-19 patients using LoC technology and clinical samples.

Published
2023

24. Cell response analysis in SARS-CoV-2 infected bronchial organoids

Author

70436567, 00422410, 60546993, 80726828, 80523993, 10759509, Sano, Emi, Suzuki, Tatsuya, Hashimoto, Rina, Itoh, Yumi, Sakamoto, Ayaka, Sakai, Yusuke, Saito, Akatsuki, Okuzaki, Daisuke, Motooka, Daisuke, Muramoto, Yukiko, Noda, Takeshi, Takasaki, Tomohiko, Sakuragi, Jun-Ichi, Minami, Shohei, Kobayashi, Takeshi, Yamamoto, Takuya, Matsumura, Yasufumi, Nagao, Miki, Okamoto, Toru, Takayama, Kazuo, 70436567, 00422410, 60546993, 80726828, 80523993, 10759509, Sano, Emi, Suzuki, Tatsuya, Hashimoto, Rina, Itoh, Yumi, Sakamoto, Ayaka, Sakai, Yusuke, Saito, Akatsuki, Okuzaki, Daisuke, Motooka, Daisuke, Muramoto, Yukiko, Noda, Takeshi, Takasaki, Tomohiko, Sakuragi, Jun-Ichi, Minami, Shohei, Kobayashi, Takeshi, Yamamoto, Takuya, Matsumura, Yasufumi, Nagao, Miki, Okamoto, Toru, and Takayama, Kazuo

Abstract

The development of an in vitro cell model that can be used to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research is expected. Here we conducted infection experiments in bronchial organoids (BO) and an BO-derived air-liquid interface model (BO-ALI) using 8 SARS-CoV-2 variants. The infection efficiency in BO-ALI was more than 1, 000 times higher than that in BO. Among the bronchial epithelial cells, we found that ciliated cells were infected with the virus, but basal cells were not. Ciliated cells died 7 days after the viral infection, but basal cells survived after the viral infection and differentiated into ciliated cells. Fibroblast growth factor 10 signaling was essential for this differentiation. These results indicate that BO and BO-ALI may be used not only to evaluate the cell response to SARS-CoV-2 and coronavirus disease 2019 (COVID-19) therapeutic agents, but also for airway regeneration studies.

Published
2022

25. Exocyst complex component 2 is a potential host factor for SARS-CoV-2 infection

Author

80726828, 80523993, 10759509, Yi, Renxing, Hashimoto, Rina, Sakamoto, Ayaka, Matsumura, Yasufumi, Nagao, Miki, Takahashi, Kazutoshi, Takayama, Kazuo, 80726828, 80523993, 10759509, Yi, Renxing, Hashimoto, Rina, Sakamoto, Ayaka, Matsumura, Yasufumi, Nagao, Miki, Takahashi, Kazutoshi, and Takayama, Kazuo

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic and spread rapidly all over the world. Because the analysis of host factors other than receptors and proteases has not been sufficiently performed, we attempted to identify and characterize host factors essential for SARS-CoV-2 infection using iPS cells and airway organoids (AO). Based on previous CRISPR screening and RNA-seq data, we found that exocyst complex component 2 (EXOC2) is one important host factor for SARS-CoV-2 infection. The intracellular SARS-CoV-2 nucleocapsid (N) expression level was decreased to 3.7 % and the virus copy number in cell culture medium was decreased to 1.6 % by EXOC2 knockdown. Consistently, immunostaining results showed that N protein-positive cells were significantly decreased by EXOC2 knockdown. We also found that EXOC2 knockdown downregulates SARS-CoV-2 infection by regulating IFNW1 expression. In conclusion, controlling the EXOC2 expression level may prevent SARS-CoV-2 infection and deserves further study.

Published
2022

26. Characteristics of the SARS-CoV-2 omicron HK.3 variant harbouring the FLip substitution

Author

Misawa, Naoko, Guo, Ziyi, Tolentino, Jarel Elgin M, Fujita, Shigeru, Pan, Lin, Suganami, Mai, Chiba, Mika, Yoshimura, Ryo, Yasuda, Kyoko, Iida, Keiko, Ohsumi, Naomi, Strange, Adam P, Tanaka, Shiho, Fukuhara, Takasuke, Tamura, Tomokazu, Suzuki, Rigel, Suzuki, Saori, Ito, Hayato, Matsuno, Keita, Sawa, Hirofumi, Nao, Naganori, Tanaka, Shinya, Tsuda, Masumi, Wang, Lei, Oda, Yoshikata, Ferdous, Zannatul, Shishido, Kenji, Nakagawa, So, Shirakawa, Kotaro, Takaori-Kondo, Akifumi, Nagata, Kayoko, Nomura, Ryosuke, Horisawa, Yoshihito, Tashiro, Yusuke, Kawai, Yugo, Takayama, Kazuo, Hashimoto, Rina, Deguchi, Sayaka, Watanabe, Yukio, Sakamoto, Ayaka, Yasuhara, Naoko, Hashiguchi, Takao, Suzuki, Tateki, Kimura, Kanako, Sasaki, Jiei, Nakajima, Yukari, Yajima, Hisano, Irie, Takashi, Kawabata, Ryoko, Tabata, Kaori, Ikeda, Terumasa, Nasser, Hesham, Shimizu, Ryo, Begum, MST Monira, Jonathan, Michael, Mugita, Yuka, Takahashi, Otowa, Ichihara, Kimiko, Ueno, Takamasa, Motozono, Chihiro, Toyoda, Mako, Saito, Akatsuki, Shofa, Maya, Shibatani, Yuki, Nishiuchi, Tomoko, Kosugi, Yusuke, Plianchaisuk, Arnon, Putri, Olivia, Uriu, Keiya, Kaku, Yu, Hinay, Alfredo A, Jr, Chen, Luo, Kuramochi, Jin, Sadamasu, Kenji, Yoshimura, Kazuhisa, Asakura, Hiroyuki, Nagashima, Mami, Ito, Jumpei, and Sato, Kei

Published
2024
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28. Usability of Polydimethylsiloxane-Based Microfluidic Devices in Pharmaceutical Research Using Human Hepatocytes

Author

Deguchi, Sayaka, primary, Tsuda, Masahiro, additional, Kosugi, Kaori, additional, Sakamoto, Ayaka, additional, Mimura, Natsumi, additional, Negoro, Ryosuke, additional, Sano, Emi, additional, Nobe, Takuro, additional, Maeda, Kazuya, additional, Kusuhara, Hiroyuki, additional, Mizuguchi, Hiroyuki, additional, Yamashita, Fumiyoshi, additional, Torisawa, Yu-suke, additional, and Takayama, Kazuo, additional

Published
2021
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29. Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

Author

70436567, 00422410, 60546993, 10759509, Sano, Emi, Deguchi, Sayaka, Sakamoto, Ayaka, Mimura, Natsumi, Hirabayashi, Ai, Muramoto, Yukiko, Noda, Takeshi, Yamamoto, Takuya, Takayama, Kazuo, 70436567, 00422410, 60546993, 10759509, Sano, Emi, Deguchi, Sayaka, Sakamoto, Ayaka, Mimura, Natsumi, Hirabayashi, Ai, Muramoto, Yukiko, Noda, Takeshi, Yamamoto, Takuya, and Takayama, Kazuo

Abstract

Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. As induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in SARS-CoV-2 infection in vitro. We found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected w SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, and production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ embryonic stem (ES) cells from eight individuals. Male iPS/ES cells were more capable of producing the virus compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro but also are a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences.

Published
2021

30. Dual inhibition of TMPRSS2 and Cathepsin B prevents SARS-CoV-2 infection in iPS cells

Author

50578002, 10295694, 10759509, Hashimoto, Rina, Sakamoto, Ayaka, Deguchi, Sayaka, Yi, Renxing, Sano, Emi, Hotta, Akitsu, Takahashi, Kazutoshi, Yamanaka, Shinya, Takayama, Kazuo, 50578002, 10295694, 10759509, Hashimoto, Rina, Sakamoto, Ayaka, Deguchi, Sayaka, Yi, Renxing, Sano, Emi, Hotta, Akitsu, Takahashi, Kazutoshi, Yamanaka, Shinya, and Takayama, Kazuo

Abstract

It has been reported that many receptors and proteases are required for SARS-CoV-2 infection. Although angiotensin-converting enzyme2 (ACE2) is the most important of these receptors, little is known about the contribution of other genes. In this study, we examined the roles of neuropilin-1, basigin, transmembrane serine proteases (TMPRSSs), and cathepsins (CTSs) in SARS-CoV-2 infection using the CRISPR interference system and ACE2-expressing human iPS cells. Double-knockdown of TMPRSS2 and CTSB reduced the viral load to 0.036±0.021%. Consistently, the combination of the CTPB inhibitor CA-074 methyl ester and the TMPRSS2 inhibitor Camostat reduced the viral load to 0.0078±0.0057%. This result was confirmed using four SARS-CoV-2 variants (B.1.3, B.1.1.7, B.1.351, and B.1.1.248). The simultaneous use of these two drugs reduced viral load to less than 0.01% in both female and male iPS cells. These findings suggest that compounds targeting TMPRSS2 and CTSB exhibit highly efficient antiviral effects independent of gender and SARS-CoV-2 variant.

Published
2021

32. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J‐SSCG 2020)

Author

Egi, Moritoki, primary, Ogura, Hiroshi, additional, Yatabe, Tomoaki, additional, Atagi, Kazuaki, additional, Inoue, Shigeaki, additional, Iba, Toshiaki, additional, Kakihana, Yasuyuki, additional, Kawasaki, Tatsuya, additional, Kushimoto, Shigeki, additional, Kuroda, Yasuhiro, additional, Kotani, Joji, additional, Shime, Nobuaki, additional, Taniguchi, Takumi, additional, Tsuruta, Ryosuke, additional, Doi, Kent, additional, Doi, Matsuyuki, additional, Nakada, Taka‐aki, additional, Nakane, Masaki, additional, Fujishima, Seitaro, additional, Hosokawa, Naoto, additional, Masuda, Yoshiki, additional, Matsushima, Asako, additional, Matsuda, Naoyuki, additional, Yamakawa, Kazuma, additional, Hara, Yoshitaka, additional, Sakuraya, Masaaki, additional, Ohshimo, Shinichiro, additional, Aoki, Yoshitaka, additional, Inada, Mai, additional, Umemura, Yutaka, additional, Kawai, Yusuke, additional, Kondo, Yutaka, additional, Saito, Hiroki, additional, Taito, Shunsuke, additional, Takeda, Chikashi, additional, Terayama, Takero, additional, Tohira, Hideo, additional, Hashimoto, Hideki, additional, Hayashida, Kei, additional, Hifumi, Toru, additional, Hirose, Tomoya, additional, Fukuda, Tatsuma, additional, Fujii, Tomoko, additional, Miura, Shinya, additional, Yasuda, Hideto, additional, Abe, Toshikazu, additional, Andoh, Kohkichi, additional, Iida, Yuki, additional, Ishihara, Tadashi, additional, Ide, Kentaro, additional, Ito, Kenta, additional, Ito, Yusuke, additional, Inata, Yu, additional, Utsunomiya, Akemi, additional, Unoki, Takeshi, additional, Endo, Koji, additional, Ouchi, Akira, additional, Ozaki, Masayuki, additional, Ono, Satoshi, additional, Katsura, Morihiro, additional, Kawaguchi, Atsushi, additional, Kawamura, Yusuke, additional, Kudo, Daisuke, additional, Kubo, Kenji, additional, Kurahashi, Kiyoyasu, additional, Sakuramoto, Hideaki, additional, Shimoyama, Akira, additional, Suzuki, Takeshi, additional, Sekine, Shusuke, additional, Sekino, Motohiro, additional, Takahashi, Nozomi, additional, Takahashi, Sei, additional, Takahashi, Hiroshi, additional, Tagami, Takashi, additional, Tajima, Goro, additional, Tatsumi, Hiroomi, additional, Tani, Masanori, additional, Tsuchiya, Asuka, additional, Tsutsumi, Yusuke, additional, Naito, Takaki, additional, Nagae, Masaharu, additional, Nagasawa, Ichiro, additional, Nakamura, Kensuke, additional, Nishimura, Tetsuro, additional, Nunomiya, Shin, additional, Norisue, Yasuhiro, additional, Hashimoto, Satoru, additional, Hasegawa, Daisuke, additional, Hatakeyama, Junji, additional, Hara, Naoki, additional, Higashibeppu, Naoki, additional, Furushima, Nana, additional, Furusono, Hirotaka, additional, Matsuishi, Yujiro, additional, Matsuyama, Tasuku, additional, Minematsu, Yusuke, additional, Miyashita, Ryoichi, additional, Miyatake, Yuji, additional, Moriyasu, Megumi, additional, Yamada, Toru, additional, Yamada, Hiroyuki, additional, Yamamoto, Ryo, additional, Yoshida, Takeshi, additional, Yoshida, Yuhei, additional, Yoshimura, Jumpei, additional, Yotsumoto, Ryuichi, additional, Yonekura, Hiroshi, additional, Wada, Takeshi, additional, Watanabe, Eizo, additional, Aoki, Makoto, additional, Asai, Hideki, additional, Abe, Takakuni, additional, Igarashi, Yutaka, additional, Iguchi, Naoya, additional, Ishikawa, Masami, additional, Ishimaru, Go, additional, Isokawa, Shutaro, additional, Itakura, Ryuta, additional, Imahase, Hisashi, additional, Imura, Haruki, additional, Irinoda, Takashi, additional, Uehara, Kenji, additional, Ushio, Noritaka, additional, Umegaki, Takeshi, additional, Egawa, Yuko, additional, Enomoto, Yuki, additional, Ota, Kohei, additional, Ohchi, Yoshifumi, additional, Ohno, Takanori, additional, Ohbe, Hiroyuki, additional, Oka, Kazuyuki, additional, Okada, Nobunaga, additional, Okada, Yohei, additional, Okano, Hiromu, additional, Okamoto, Jun, additional, Okuda, Hiroshi, additional, Ogura, Takayuki, additional, Onodera, Yu, additional, Oyama, Yuhta, additional, Kainuma, Motoshi, additional, Kako, Eisuke, additional, Kashiura, Masahiro, additional, Kato, Hiromi, additional, Kanaya, Akihiro, additional, Kaneko, Tadashi, additional, Kanehata, Keita, additional, Kano, Ken‐ichi, additional, Kawano, Hiroyuki, additional, Kikutani, Kazuya, additional, Kikuchi, Hitoshi, additional, Kido, Takahiro, additional, Kimura, Sho, additional, Koami, Hiroyuki, additional, Kobashi, Daisuke, additional, Saiki, Iwao, additional, Sakai, Masahito, additional, Sakamoto, Ayaka, additional, Sato, Tetsuya, additional, Shiga, Yasuhiro, additional, Shimoto, Manabu, additional, Shimoyama, Shinya, additional, Shoko, Tomohisa, additional, Sugawara, Yoh, additional, Sugita, Atsunori, additional, Suzuki, Satoshi, additional, Suzuki, Yuji, additional, Suhara, Tomohiro, additional, Sonota, Kenji, additional, Takauji, Shuhei, additional, Takashima, Kohei, additional, Takahashi, Sho, additional, Takahashi, Yoko, additional, Takeshita, Jun, additional, Tanaka, Yuuki, additional, Tampo, Akihito, additional, Tsunoyama, Taichiro, additional, Tetsuhara, Kenichi, additional, Tokunaga, Kentaro, additional, Tomioka, Yoshihiro, additional, Tomita, Kentaro, additional, Tominaga, Naoki, additional, Toyosaki, Mitsunobu, additional, Toyoda, Yukitoshi, additional, Naito, Hiromichi, additional, Nagata, Isao, additional, Nagato, Tadashi, additional, Nakamura, Yoshimi, additional, Nakamori, Yuki, additional, Nahara, Isao, additional, Naraba, Hiromu, additional, Narita, Chihiro, additional, Nishioka, Norihiro, additional, Nishimura, Tomoya, additional, Nishiyama, Kei, additional, Nomura, Tomohisa, additional, Haga, Taiki, additional, Hagiwara, Yoshihiro, additional, Hashimoto, Katsuhiko, additional, Hatachi, Takeshi, additional, Hamasaki, Toshiaki, additional, Hayashi, Takuya, additional, Hayashi, Minoru, additional, Hayamizu, Atsuki, additional, Haraguchi, Go, additional, Hirano, Yohei, additional, Fujii, Ryo, additional, Fujita, Motoki, additional, Fujimura, Naoyuki, additional, Funakoshi, Hiraku, additional, Horiguchi, Masahito, additional, Maki, Jun, additional, Masunaga, Naohisa, additional, Matsumura, Yosuke, additional, Mayumi, Takuya, additional, Minami, Keisuke, additional, Miyazaki, Yuya, additional, Miyamoto, Kazuyuki, additional, Murata, Teppei, additional, Yanai, Machi, additional, Yano, Takao, additional, Yamada, Kohei, additional, Yamada, Naoki, additional, Yamamoto, Tomonori, additional, Yoshihiro, Shodai, additional, Tanaka, Hiroshi, additional, and Nishida, Osamu, additional

Published
2021
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39. Dual inhibition of TMPRSS2 and Cathepsin Bprevents SARS-CoV-2 infection in iPS cells.

Author

Hashimoto R, Sakamoto A, Deguchi S, Yi R, Sano E, Hotta A, Takahashi K, Yamanaka S, and Takayama K

Abstract

It has been reported that many receptors and proteases are required for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Although angiotensin-converting enzyme 2 (ACE2) is the most important of these receptors, little is known about the contribution of other genes. In this study, we examined the roles of neuropilin-1, basigin, transmembrane serine proteases (TMPRSSs), and cathepsins (CTSs) in SARS-CoV-2 infection using the CRISPR interference system and ACE2-expressing human induced pluripotent stem (iPS) cells. Double knockdown of TMPRSS2 and cathepsin B (CTSB) reduced the viral load to 0.036% ± 0.021%. Consistently, the combination of the CTPB inhibitor CA-074 methyl ester and the TMPRSS2 inhibitor camostat reduced the viral load to 0.0078% ± 0.0057%. This result was confirmed using four SARS-CoV-2 variants (B.1.3, B.1.1.7, B.1.351, and B.1.1.248). The simultaneous use of these two drugs reduced viral load to less than 0.01% in both female and male iPS cells. These findings suggest that compounds targeting TMPRSS2 and CTSB exhibit highly efficient antiviral effects independent of gender and SARS-CoV-2 variant., Competing Interests: K. Takahashi is on the scientific advisory board of I Peace, without salary. S.Y. is a scientific advisor, without salary, to iPS Academia Japan and Altos Labs. The other authors declare no competing financial interests., (© 2021 The Author(s).)

Published
2021
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