Vitamin D and COVID-19: A review on the role of vitamin D in preventing and reducing the severity of COVID-19 infection

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a pathogenic coronavirus causing COVID-19 infection. The interaction between the SARS-CoV-2 spike protein and the human receptor angiotensin-converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide-thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID-19. However, the molecular-level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID-19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID-19 infection or reducing the severity of the disease.

Keywords: COVID-19; SARS-CoV-2; cholecalciferol; oxidative stress; vitamin D.

FIGURE 1

Structure of 1,25‐dihydroxycholecalciferol, the active form of vitamin D₃. The A ring (a) is connected to the CD‐ring system (c) by a triene system (b). The A ring mediates the interactions with the vitamin D receptor

FIGURE 2

The pathway from angiotensinogen to angiotensin 1–7 is shown, along with the enzymes that catalyze these reactions

FIGURE 3

Redox enzymes involved in detoxifying superoxide ion

FIGURE 4

Thiol‐disulfide exchange reaction catalyzed by thioredoxin 1 (Trx1). The black arrows indicate the flow of electron from Trx1 to substrate. As the Trx1 gets oxidized by reducing the disulfide bond of the substrate, the substrate gets reduced

FIGURE 5

Schematic representation of protein disulfide isomerase activity. (a) Disulfide bond formation is catalyzed by PDI. As PDI is reduced, the correct disulfide bonds are formed in the substrate. (b) Disulfide isomerization in the substrate is catalyzed by PDI. Reduced PDI attacks the incorrect disulfide bond in the substrate, and the correct disulfide bond is then formed