Identification of SARS-CoV-2 m6A modification sites correlate with viral pathogenicity

Ke Liu; Ying-Zi Zhang; Hui Yin; Lu-Lu Yu; Jia-Jia Cui; Ji-Ye Yin; Chen-Hui Luo; Cheng-Xian Guo

doi:10.1016/j.micinf.2023.105228

Identification of SARS-CoV-2 m6A modification sites correlate with viral pathogenicity

Microbes Infect. 2024 Jan-Feb;26(1-2):105228. doi: 10.1016/j.micinf.2023.105228. Epub 2023 Sep 20.

Authors

Ke Liu¹, Ying-Zi Zhang¹, Hui Yin², Lu-Lu Yu³, Jia-Jia Cui⁴, Ji-Ye Yin⁵, Chen-Hui Luo⁶, Cheng-Xian Guo⁷

Affiliations

¹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, China; National Clinical Research Center for Geriatric Disorders, China.
² Department of Clinical Pharmacology, Xiangya Hospital, Central South University, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, China; National Clinical Research Center for Geriatric Disorders, China; Department of Pharmacy, The Central Hospital of Shaoyang, Shaoyang, China.
³ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, China; National Clinical Research Center for Geriatric Disorders, China; Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
⁴ National Clinical Research Center for Geriatric Disorders, China; Department of Geriatric Surgery, Xiangya Hospital, Central South University, China.
⁵ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, China; National Clinical Research Center for Geriatric Disorders, China; Hunan Provincial Gynecological Cancer Diagnosis and Treatment Engineering Research Center, China.
⁶ Scientific Research Office, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, China. Electronic address: [email protected].
⁷ Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, China. Electronic address: [email protected].

PMID: 37734532
DOI: 10.1016/j.micinf.2023.105228

Abstract

It has recently been found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) m6A modifications can affect viral replication and function. However, no studies to date have shown a correlation between SARS-CoV-2 m6A modifications and viral pathogenicity. In this study, we analyzed m6A modification in 2,190,667 SARS-CoV-2 genomic RNAs. m6A modifications of SARS-CoV-2 from different lineages, causing mild or severe COVID-19 and showing breakthrough for different vaccines were analyzed to explore correlations with viral pathogenicity. The results suggested that the presence of more m6A modifications in the SARS-CoV-2 N region (positive strand) correlates with weaker pathogenicity. In addition, we identified three m6A modification sites correlating with weak pathogenicity (924 in ORF1ab, 15,659 in ORF1ab, 28,288 in N, 28,633 in N and 29,385 in N, 29,707 in 3'UTR) and one with strong pathogenicity (74 in 5'UTR). These results provide new information for understanding the prevalence of SARS-CoV-2 and controlling the virus.

Keywords: Breakthrough infection; COVID-19; SARS-CoV-2; m6A; β-coronaviruses.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenine / analogs & derivatives*
COVID-19*
Humans
SARS-CoV-2* / genetics
Virulence
Virus Replication

Substances

6-methyladenine
Adenine