{"title":"Virological characteristics correlating with SARS-CoV-2 spike protein fusogenicity","authors":"MST Monira Begum, Kimiko Ichihara, Otowa Takahashi, Hesham Nasser, Michael Jonathan, Kenzo Tokunaga, Isao Yoshida, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Kei Sato, Terumasa Ikeda, Keita Matsuno, Naganori Nao, Hirofumi Sawa, Shinya Tanaka, Masumi Tsuda, Lei Wang, Yoshikata Oda, Zannatul Ferdous, Kenji Shishido, Takasuke Fukuhara, Tomokazu Tamura, Rigel Suzuki, Saori Suzuki, Hayato Ito, Jumpei Ito, Yu Kaku, Naoko Misawa, Arnon Plianchaisuk, Ziyi Guo, Alfredo Jr. Hinay, Keiya Uriu, Yusuke Kosugi, Shigeru Fujita, Jarel Elgin Mendoza Tolentino, Luo Chen, Lin Pan6, Mai Suganami, Mika Chiba, Ryo Yoshimura, Kyoko Yasuda, Keiko Iida, Naomi Ohsumi, Adam Patrick Strange, Hiroyuki Asakura, Isao Yoshida, So Nakagawa, Akifumi Takaori-Kondo, Kotaro Shirakawa, Kayoko Nagata, Ryosuke Nomura, Yoshihito Horisawa, Yusuke Tashiro, Yugo Kawai, Kazuo Takayama, Rina Hashimoto, Sayaka Deguchi, Yukio Watanabe, Ayaka Sakamoto, Naoko Yasuhara, Takao Hashiguchi, Tateki Suzuki, Kanako Kimura, Jiei Sasaki, Yukari Nakajima, Hisano Yajima, Takashi Irie, Ryoko Kawabata, Kaori Tabata, Ryo Shimizu1, Yuka Mugita1, Takamasa Ueno, Chihiro Motozono, Mako Toyoda, Akatsuki Saito, Maya Shofa, Yuki Shibatani, Tomoko Nishiuchi","doi":"10.3389/fviro.2024.1353661","DOIUrl":null,"url":null,"abstract":"<sec><title>Introduction</title><p>The severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike (S) protein is essential in mediating membrane fusion of the virus with the target cells. Several reports demonstrated that SARS-CoV-2 S protein fusogenicity is reportedly closely associated with the intrinsic pathogenicity of the virus determined using hamster models. However, the association between S protein fusogenicity and other virological parameters remains elusive.</p></sec><sec><title>Methods</title><p>In this study, we investigated the virological parameters (e.g., S1/S2 cleavage efficiency, plaque size, pseudoviral infectivity, pseudovirus entry efficiency, and viral replication kinetics) of eleven previous variants of concern (VOCs) and variants of interest (VOIs) correlating with S protein fusogenicity.</p></sec><sec><title>Results and discussion</title><p>S protein fusogenicity was found to be strongly correlated with S1/S2 cleavage efficiency and plaque size formed by clinical isolates. However, S protein fusogenicity was less associated with pseudoviral infectivity, pseudovirus entry efficiency, and viral replication kinetics. Taken together, our results suggest that S1/S2 cleavage efficiency and plaque size could be potential indicators to predict the intrinsic pathogenicity and S protein fusogenicity of newly emerged SARS-CoV-2 variants.</p></sec>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"33 1","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in virology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fviro.2024.1353661","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"VIROLOGY","Score":null,"Total":0}
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Abstract
Introduction
The severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike (S) protein is essential in mediating membrane fusion of the virus with the target cells. Several reports demonstrated that SARS-CoV-2 S protein fusogenicity is reportedly closely associated with the intrinsic pathogenicity of the virus determined using hamster models. However, the association between S protein fusogenicity and other virological parameters remains elusive.
Methods
In this study, we investigated the virological parameters (e.g., S1/S2 cleavage efficiency, plaque size, pseudoviral infectivity, pseudovirus entry efficiency, and viral replication kinetics) of eleven previous variants of concern (VOCs) and variants of interest (VOIs) correlating with S protein fusogenicity.
Results and discussion
S protein fusogenicity was found to be strongly correlated with S1/S2 cleavage efficiency and plaque size formed by clinical isolates. However, S protein fusogenicity was less associated with pseudoviral infectivity, pseudovirus entry efficiency, and viral replication kinetics. Taken together, our results suggest that S1/S2 cleavage efficiency and plaque size could be potential indicators to predict the intrinsic pathogenicity and S protein fusogenicity of newly emerged SARS-CoV-2 variants.
导言严重急性呼吸系统综合症冠状病毒（SARS-CoV-2）的尖峰（S）蛋白在介导病毒与靶细胞的膜融合中起着至关重要的作用。一些报道表明，SARS-CoV-2 S 蛋白的融合性与利用仓鼠模型测定的病毒内在致病性密切相关。本研究调查了病毒学参数（如：S1/S2裂解效率、S1/S2裂解率、S1/S2裂解率、S1/S2裂解率、S1/S2裂解率、S1/S2裂解率、S1/S2裂解率、S1/S2裂解率）、结果与讨论发现S蛋白致熔性与临床分离株形成的S1/S2裂解效率和斑块大小密切相关。然而，S 蛋白致熔性与假病毒感染性、假病毒进入效率和病毒复制动力学的相关性较低。综上所述，我们的研究结果表明，S1/S2裂解效率和斑块大小可能是预测新出现的SARS-CoV-2变异株的内在致病性和S蛋白致熔性的潜在指标。
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