Protective Role of Vitamin K3 on SARS-CoV-2 Structural Protein-Induced Inflammation and Cell Death

Abstract

The structure proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as nucleocapsid protein (N protein) and envelop protein (E protein), are considered to be the critical pro-inflammatory factors in coronavirus disease 2019 (COVID-19). Vitamin K3 has been reported to exert an anti-inflammatory effect. In this study, we investigated the protective effects of vitamin K3 on SARS-CoV-2 N protein induced-endothelial activation and SARS-CoV-2 E protein induced-cell death in THP-1 cells. The results showed that vitamin K3 reduced N protein-induced monocyte adhesion, suppressed the expression of adhesion molecules, and decreased the mRNA levels of pro-inflammatory cytokines in HLMECs. We confirmed that the effects of vitamin K3 on endothelial activation may be related to the inhibition of the NF-κB signal pathway. In addition, vitamin K3 reversed E protein-induced pyroptosis, inhibited NLRP3/GSDMD signal pathway and reduced the mRNA expression of pro-inflammatory cytokines in THP-1 cells. Our results also showed the protective effects of vitamin K3 on the SARS-CoV-2 structural protein-induced THP-1 cells pyroptosis and endothelial activation via NF-κB signaling pathway. These findings suggested that vitamin K3 potently suppressed the inflammatory response to prevent endothelial activation and monocyte pyroptosis induced by SARS-CoV-2 proteins. This may provide a new strategy for the treatment of COVID-19.

Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial

“…Vitamin K may also impact the progression of COVID-19 in other ways. A recent study reported on the potential protective effects of vitamin K3—a synthetic form of vitamin K—on SARS-CoV-2-induced inflammation and cell damage [ 39 ]. The authors demonstrated that vitamin K3 might have beneficial effects on SARS-CoV-2 E protein-induced-cell death (pyroptosis) and reduced N protein-induced monocyte adhesion [ 39 ].…”

“…A recent study reported on the potential protective effects of vitamin K3—a synthetic form of vitamin K—on SARS-CoV-2-induced inflammation and cell damage [ 39 ]. The authors demonstrated that vitamin K3 might have beneficial effects on SARS-CoV-2 E protein-induced-cell death (pyroptosis) and reduced N protein-induced monocyte adhesion [ 39 ]. Staufer et al suggest that vitamin K may directly bind the SARS-CoV-2 free fatty acid-binding pocket (FABP), potentially impacting infectivity [ 40 ].…”