Folic acid restricts SARS-CoV-2 invasion by methylating ACE2

Yuanzhou Zhang; Yechun Pang; Baiyin Xu; Xingshi Chen; Shunshun Liang; Jingying Hu; Xiaoying Luo

doi:10.3389/fmicb.2022.980903

Folic acid restricts SARS-CoV-2 invasion by methylating ACE2

Front Microbiol. 2022 Aug 17:13:980903. doi: 10.3389/fmicb.2022.980903. eCollection 2022.

Authors

Yuanzhou Zhang¹, Yechun Pang¹, Baiyin Xu², Xingshi Chen¹, Shunshun Liang¹, Jingying Hu¹, Xiaoying Luo¹

Affiliations

¹ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Pudong New Area People's Hosptial, Shanghai, China.

Abstract

The current COVID-19 pandemic is motivating us to elucidate the molecular mechanism of SARS-CoV-2 invasion and find methods for decreasing its transmissibility. We found that SARS-CoV-2 could increase the protein level of ACE2 in mice. Folic acid and 5-10-methylenetetrahydrofolate reductase (MTHFR) could promote the methylation of the ACE2 promoter and inhibit ACE2 expression. Folic acid treatment decreased the binding ability of Spike protein, pseudovirus and inactivated authentic SARS-CoV-2 to host cells. Thus, folic acid treatment could decrease SARS-CoV-2 invasion and SARS-CoV-2-neutralizing antibody production in mice. These data suggest that increased intake of folic acid may inhibit ACE2 expression and reduce the transmissibility of SARS-CoV-2. Folic acid could play an important role in SARS-CoV-2 infection prevention and control.

Keywords: ACE2; MTHFR; SARS-CoV-2; folic acid; methylation.