Hydrophobic Alpha-Helical Short Peptides in Overlapping Reading Frames of the Coronavirus Genome
Takashi Okura,
Kazuya Shirato,
Masatoshi Kakizaki,
Satoko Sugimoto,
Shutoku Matsuyama,
Tomohisa Tanaka,
Yohei Kume,
Mina Chishiki,
Takashi Ono,
Kohji Moriishi,
Masashi Sonoyama,
Mitsuaki Hosoya,
Koichi Hashimoto,
Katsumi Maenaka,
Makoto Takeda
Affiliations
Takashi Okura
Department of Virology 3, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan
Kazuya Shirato
Department of Virology 3, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan
Masatoshi Kakizaki
Department of Virology 3, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan
Satoko Sugimoto
Department of Virology 3, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan
Shutoku Matsuyama
Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan
Tomohisa Tanaka
Department of Microbiology, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Chuo 409-3898, Yamanashi, Japan
Yohei Kume
Department of Pediatrics, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Fukushima, Japan
Mina Chishiki
Department of Pediatrics, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Fukushima, Japan
Takashi Ono
Department of Pediatrics, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Fukushima, Japan
Kohji Moriishi
Department of Microbiology, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Chuo 409-3898, Yamanashi, Japan
Masashi Sonoyama
Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu 376-8515, Gunma, Japan
Mitsuaki Hosoya
Department of Pediatrics, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Fukushima, Japan
Koichi Hashimoto
Department of Pediatrics, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Fukushima, Japan
Katsumi Maenaka
Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Hokkaido, Japan
Makoto Takeda
Department of Virology 3, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan
In this study, we show that the coronavirus (CoV) genome may encode many functional hydrophobic alpha-helical peptides (HAHPs) in overlapping reading frames of major coronaviral proteins throughout the entire viral genome. These HAHPs can theoretically be expressed from non-canonical sub-genomic (sg)RNAs that are synthesized in substantial amounts in infected cells. We selected and analyzed five and six HAHPs encoded in the S gene regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Two and three HAHPs derived from SARS-CoV-2 and MERS-CoV, respectively, specifically interacted with both the SARS-CoV-2 and MERS-CoV S proteins and inhibited their membrane fusion activity. Furthermore, one of the SARS-CoV-2 HAHPs specifically inhibited viral RNA synthesis by accumulating at the site of viral RNA synthesis. Our data show that a group of HAHPs in the coronaviral genome potentially has a regulatory role in viral propagation.
