AUTHOR=Begum MST Monira , Ichihara Kimiko , Takahashi Otowa , Nasser Hesham , Jonathan Michael , Tokunaga Kenzo , Yoshida Isao , Nagashima Mami , Sadamasu Kenji , Yoshimura Kazuhisa , The Genotype to Phenotype Japan (G2P-Japan) Consortium , Sato Kei , Ikeda Terumasa , Matsuno Keita , Nao Naganori , Sawa Hirofumi , Tanaka Shinya , Tsuda Masumi , Wang Lei , Oda Yoshikata , Ferdous Zannatul , Shishido Kenji , Fukuhara Takasuke , Tamura Tomokazu , Suzuki Rigel , Suzuki Saori , Ito Hayato , Ito Jumpei , Kaku Yu , Misawa Naoko , Plianchaisuk Arnon , Guo Ziyi , Hinay Alfredo Jr. , Uriu Keiya , Kosugi Yusuke , Fujita Shigeru , Tolentino Jarel Elgin Mendoza , Chen Luo , Pan6 Lin , Suganami Mai , Chiba Mika , Yoshimura Ryo , Yasuda Kyoko , Iida Keiko , Ohsumi Naomi , Strange Adam Patrick , Asakura Hiroyuki , Yoshida Isao , Nakagawa So , Takaori-Kondo Akifumi , Shirakawa Kotaro , 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 , Shimizu1 Ryo , Mugita1 Yuka , Ueno Takamasa , Motozono Chihiro , Toyoda Mako , Saito Akatsuki , Shofa Maya , Shibatani Yuki , Nishiuchi Tomoko TITLE=Virological characteristics correlating with SARS-CoV-2 spike protein fusogenicity JOURNAL=Frontiers in Virology VOLUME=4 YEAR=2024 URL=https://www.frontiersin.org/journals/virology/articles/10.3389/fviro.2024.1353661 DOI=10.3389/fviro.2024.1353661 ISSN=2673-818X 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.