d-Alanine as a biomarker and a therapeutic option for severe influenza virus infection and COVID-19

Shihoko Kimura-Ohba; Masamitsu N Asaka; Daichi Utsumi; Yoshitsugu Takabatake; Atsushi Takahashi; Yasuhiro Yasutomi; Yoshitaka Isaka; Tomonori Kimura

doi:10.1016/j.bbadis.2022.166584

d-Alanine as a biomarker and a therapeutic option for severe influenza virus infection and COVID-19

Biochim Biophys Acta Mol Basis Dis. 2023 Jan 1;1869(1):166584. doi: 10.1016/j.bbadis.2022.166584. Epub 2022 Oct 21.

Authors

Shihoko Kimura-Ohba¹, Masamitsu N Asaka², Daichi Utsumi², Yoshitsugu Takabatake³, Atsushi Takahashi³, Yasuhiro Yasutomi², Yoshitaka Isaka³, Tomonori Kimura⁴

Affiliations

¹ Reverse Translational Research Project, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 567-0085, Japan; KAGAMI Project, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 567-0085, Japan.
² Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 305-0843, Japan.
³ Department of Nephrology, Osaka University Graduate School of Medicine, 565-0871, Japan.
⁴ Reverse Translational Research Project, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 567-0085, Japan; KAGAMI Project, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 567-0085, Japan; Department of Nephrology, Osaka University Graduate School of Medicine, 565-0871, Japan. Electronic address: t-kimura@nibiohn.go.jp.

Abstract

Since the outbreak of coronavirus disease 2019 (COVID-19), biomarkers for evaluating severity, as well as supportive care to improve clinical course, remain insufficient. We explored the potential of d-amino acids, rare enantiomers of amino acids, as biomarkers for assessing disease severity and as protective nutrients against severe viral infections. In mice infected with influenza A virus (IAV) and in patients with severe COVID-19 requiring artificial ventilation or extracorporeal membrane oxygenation, blood levels of d-amino acids, including d-alanine, were reduced significantly compared with those of uninfected mice or healthy controls. In mice models of IAV infection or COVID-19, supplementation with d-alanine alleviated severity of clinical course, and mice with sustained blood levels of d-alanine showed favorable prognoses. In severe viral infections, blood levels of d-amino acids, including d-alanine, decrease, and supplementation with d-alanine improves prognosis. d-Alanine has great potentials as a biomarker and a therapeutic option for severe viral infections.

Keywords: Biomarker; Coronavirus disease 2019 (COVID-19); Influenza A virus; SARS-CoV-2; Survival; Treatment; d-Alanine.

Publication types

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

MeSH terms

Alanine / therapeutic use
Animals
Biomarkers
COVID-19 Drug Treatment*
Communicable Diseases*
Humans
Influenza, Human* / drug therapy
Mice
SARS-CoV-2

Substances

Alanine
Biomarkers