Salivary levels of cell cycle regulatory proteins p53, cyclin D1, CDK 4 and protein carbonylation in post COVID-19 cohort – An observational study

Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for causing the coronavirus disease 2019 (COVID-19) pandemic that brought the world to a standstill in 2019, enters human cells by angiotensin-converting enzyme 2 (ACE2) receptors. The virus binds to ACE2 using the spike-like protein on its surface. ACE2 receptors also play an essential role in promoting the proliferation and invasion of oral squamous cell carcinoma (OSCC) cells by converting Angiotensin I, which binds to its type 1 or type 2 receptor inducing anti-apoptotic and anti-oxidative stress phenotypes. This study aimed to assess the long-term effects of SARS-CoV-2 by determining its effect on cell cycle regulatory proteins p53, cyclin D1, cyclin-dependent kinase 4 (CDK 4) and protein carbonylation in saliva.

Objective

To estimate and correlate the levels of p53, cyclin D1, CDK 4 and protein carbonylation measured at baseline and 6 months follow-up among post COVID-19 cohort.

Method

The study was conducted among 40 outpatients who were diagnosed with SARS-CoV-2 between January 2022 and February 2022. The study commenced after Institutional Ethics Committee clearance. The study comprised 40 post-COVID patients who were tested positive for COVID-19. Unstimulated whole saliva samples were collected from study participants by spitting method at baseline and 6 months. p53, cyclin D1, CDK 4 and protein carbonylation expression were assessed using ELISA. The obtained data were subjected to statistical analysis.

Results

The levels of proteins p53, cyclin D1, CDK 4 and protein carbonylation measured at baseline and six months were (687.02 ± 88.15 and 801.59 ± 82.72), (36.27 ± 5.04 and 45.71 ± 4.78), (9.25 ± 1.92 9.71 ± 0.98) and (864.76 ± 171.29 and 960.15 ± 82.03) respectively. There was a significant increase in levels of p53 (p < 0.05), cyclin D1 (p < 0.05), and protein carbonylation (p < 0.05) from baseline to 6 months.

Conclusion

An increase in salivary levels of p53, cyclin D1, CDK 4 and protein carbonylation suggests that there may be long-term effects of SARS-CoV-2 on cell cycle regulatory proteins. Over-expression of these markers does not signify that these patients are likely to get OSCC in the future instead, there may be some retained long-term effects of the virus whose mechanism yet needs to be understood. Further, transcriptomic profiling of tumor suppressor proteins may give us interesting results on the long-term effects of SARS-CoV-2.