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

doi:10.3390/pathogens11080877

Hydrophobic Alpha-Helical Short Peptides in Overlapping Reading Frames of the Coronavirus Genome

Pathogens. 2022 Aug 3;11(8):877. doi: 10.3390/pathogens11080877.

Authors

Takashi Okura¹, Kazuya Shirato¹, Masatoshi Kakizaki¹, Satoko Sugimoto^{1

2}, Shutoku Matsuyama³, Tomohisa Tanaka⁴, Yohei Kume⁵, Mina Chishiki⁵, Takashi Ono⁵, Kohji Moriishi^{4

6

7}, Masashi Sonoyama^{8

9

10}, Mitsuaki Hosoya⁵, Koichi Hashimoto⁵, Katsumi Maenaka^{11

12

13}, Makoto Takeda¹

Affiliations

¹ Department of Virology 3, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan.
² Management Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan.
³ Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Musashimurayama 208-0011, Tokyo, Japan.
⁴ Department of Microbiology, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Chuo 409-3898, Yamanashi, Japan.
⁵ Department of Pediatrics, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Fukushima, Japan.
⁶ Center for Life Science Research, University of Yamanashi, Chuo 409-3898, Yamanashi, Japan.
⁷ Division of Hepatitis Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0808, Hokkaido, Japan.
⁸ Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu 376-8515, Gunma, Japan.
⁹ Gunma University Center for Food Science and Wellness (GUCFW), Gunma University, Kiryu 376-8515, Gunma, Japan.
¹⁰ Gunma University Initiative for Advanced Research (GIAR), Gunma University, Kiryu 376-8515, Gunma, Japan.
¹¹ Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Hokkaido, Japan.
¹² Center for Research and Education on Drug Discovery, Hokkaido University, Sapporo 060-0812, Hokkaido, Japan.
¹³ Global Station for Biosurfaces and Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Hokkaido, Japan.

Abstract

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.

Keywords: SARS-CoV-2; alpha-helix; coronavirus; nidovirus; overlapping frame; sub-genomic RNA.

Abstract

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