SARS-CoV-2 Structural Proteins Affects Oral Health By Causing Periodontal Fibrosis


A new study by researchers from the University of Plymouth-UK has alarmingly found that SARS-CoV-2 structural proteins affects oral health by causing periodontal fibrosis via deregulating mitochondrial b-oxidation.

The study findings were published on a preprint server and are currently being peer reviewed.

COVID-19 infection can cause a series of symptoms. Among them, fibrosis particularly in lung tissues has evoked significant attention due to the severe consequence on patient life and health quality. Although the current dominant SARS-CoV-2 variants (such as the Omicron) induce milder symptoms in human bodies, the exact pathological consequence of COVID-19 to different human tissues and organs, particularly for oral cavity tissues are still missing.

Current concepts of COVID-19 etiology suggest lung fibrosis caused by SARS-CoV-2 infection can be mainly due to damages on lung epithelial cells that trigger acute inflammation followed by fibroblast hyperproliferation (Merad and Martin 2020). However, as SARS-CoV-2 infection is rapid and it is difficult to distinguish if the deeper cells (such as fibroblasts) can also be infected directly.

We therefore cannot neglect the potential direct infection of fibroblasts by SARS-CoV-2. In particular, PDL is one of the most vulnerable human tissues that extrinsic virus and bacteria can often enter PDL directly in pathological conditions (Kononen et al. 2019). As such, it is reasonable to postulate that SARS-CoV-2 can also directly infect PDL fibroblasts in the already damaged PDL and induce further pathological changes.

Attentions should be made by dental clinicians to the patients who got COVID-19 and appeared to be diagnosed with periodontal disease at the same time, particularly for those long COVID and repeated infected cases.

Our results also suggested SARS-CoV-2 infection indeed can directly induce fibrotic disease phenotypes in fibroblasts through distinct pathways. Mitochondrial fatty acid β-oxidation is the major pathway responsible for fatty acids degradation, hence is essential for human body energy homeostasis. Impeding the pathway can cause different disorders (Merritt et al. 2018).

Very recent studies have observed mitochondrial dysregulation in COVID-19 patient blood cells (Ajaz et al. 2021; Guntur et al. 2022). Interestingly, the dysfunction of the fatty acid oxidation has been previously connected with fibrosis particularly in the lung and kidney (Geng et al. 2021; Jang et al. 2020){Merritt, 2018 #12}.

For the first time, our findings further confirmed that in the fibroblasts, SARS-CoV-2 could induce fibrotic degeneration directly, through down-regulating fatty acid β-oxidation, particularly by the virus’ envelope and membrane proteins.

Among the SARS-CoV-2’s structural proteins: envelope, membrane, nucleocapsid and spike, the first three proteins are stable structure proteins for all the reported variants, while so far all of the identified mutations happen inside the spike proteins (Harvey et al. 2021).

Although spike protein is still the target especially for COVID-19 vaccine development, increasing evidence suggest the other SARS-CoV-2 structural proteins might have unexpected important roles in inducing COVID-19 symptoms. Previous structural analysis of the envelope protein suggested it might be important for virus pathogenicity (Mandala et al. 2020).

The envelope protein can also physically increase intra-Golgi pH and forms cation channel(Cabrera-Garcia et al. 2021), and biochemically modulate spike protein in the meantime (Boson et al. 2021). The most abundant protein: the membrane protein in the SARS-CoV-2 virus, is rationally important for virus assembly (Zhang et al. 2022).

Our results further confirmed that the envelope and membrane proteins are actually responsible for the fibrosis phenotypes in the cells by down regulating the key fatty acid β-oxidation regulator such as the trifunctional enzyme subunit alpha. The molecular mechanism behind this regulation axis would require further biochemical analysis.

In this study, our results provide novel mechanistic insights into how SARS-CoV-2 infection can affect human health, particularly for inducing fibrosis, at the cell and molecular level. The findings could be possibly extended to the other body systems to explain and explore the fibrosis pathology and treatment.


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