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. 2021 Apr:149:110543.
doi: 10.1016/j.mehy.2021.110543. Epub 2021 Feb 18.

COVID-19: A methyl-group assault?

Andrew McCaddon  1 , Björn Regland  2
Affiliations

COVID-19: A methyl-group assault?

Andrew McCaddon et al. Med Hypotheses. 2021 Apr.

Abstract

The socio-economic implications of COVID-19 are devastating. Considerable morbidity is attributed to 'long-COVID' - an increasingly recognized complication of infection. Its diverse symptoms are reminiscent of vitamin B12 deficiency, a condition in which methylation status is compromised. We suggest why SARS-CoV-2 infection likely leads to increased methyl-group requirements and other disturbances of one-carbon metabolism. We propose these might explain the varied symptoms of long-COVID. Our suggested mechanismmight also apply to similar conditions such as myalgic encephalomyelitis/chronic fatigue syndrome. The hypothesis is evaluable by detailed determination of vitamin B12and folate status, including serum formate as well as homocysteine and methylmalonic acid, and correlation with viral and host RNA methylation and symptomatology. If confirmed, methyl-group support should prove beneficial in such individuals.

Keywords: COVID-19; Coronavirus; Folic acid; Formate; N6-methyladenosine (m6A); Serine; Vitamin B(12).

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
One-carbon metabolism.
Fig. 2
Fig. 2
In the primary turnover cycle of the MS reaction, homocysteine reacts with the methyl (CH3) group of MS-bound methylcobalamin to produce methionine and an unstable intermediate form of vitamin B12, cob(I)alamin (upper bold arrow). This highly reactive species then reacts with methyl-tetrahydrofolate (methyl-THF) to generate free THF and regenerate MS-bound methylcobalamin (lower bold arrow). Cobalamin therefore shuttles between methylcobalamin and cob(I)alamin states. Cob(I) alamin is occasionally de-activated by reactive oxygen species (ROS) and oxidised to cob(II)alamin (dashed arrows). The return of cob(II)alamin to the primary turnover cycle requires a re-activation step in which SAM provides the methyl group (lateral bold arrows). De-activation and re-activation usually occur every few thousand cycles. We suggest this process is significantly augmented with SARS-CoV-2 infection.
Fig. 3
Fig. 3
GSH-dependent metabolism of formaldehyde, and the intracellular fate of formate.
See this image and copyright information in PMC

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