COVID-19 Research: Scripps Research Indicates That Host Cells Laden With Cholesterol Enhances Facilitation Of SARS-CoV-2 Viral Entry
COVID-19 Research: Researchers from the department of molecular medicine at Scripps Research Institute - Florida in a new study have discovered that cholesterol saturation in host cells helps to facilitate viral entry of the SARS-CoV-2 coronavirus.
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Their research findings were published on a preprint server but are yet to have been peer-reviewed.
https://www.biorxiv.org/content/10.1101/2020.05.09.086249v3
COVID-19 is a respiratory infection caused by SARS-CoV-2 originating in Wuhan China in 2019. The disease in notably severe in elderly and those with underlying chronic conditions such as obesity, diabetes, high-blood pressure and cardiovascular issues.
The molecular mechanism as to why the elderly are vulnerable and why children are resistant is largely unknown. Understanding these differences is critical for safeguarding the vulnerable and guiding effective policy and treatments.
In the study, the researchers comprising Dr Hao Wang, Dr Zixuan Yuan, Dr Mahmud Arif Pavel and Dr Scott B. Hansen all from the Department of molecular medicine at Scripps showed loading cells with cholesterol from blood serum using the cholesterol transport protein apolipoprotein E (apoE) enhances the endocytic entry of pseudotyped SARS-CoV-2.
Super resolution imaging of the SARS-CoV-2 entry point with high cholesterol showed markedly increased apparent diameter (~10% to 100 nm) and almost twice the total number of viral entry points.
It was observed that the cholesterol concomitantly traffics angiotensinogen converting enzyme (ACE2) to the viral entry site where SARS-CoV-2 docks to properly exploit entry into the cell.
The researchers also discovered that cholesterol enhances binding of SARS-CoV-2 to the cell surface which increases association with the endocytic pathway. Decreasing cellular cholesterol has the opposite effect.
In mouse lungs, the study team found that age and high fat diet induced cholesterol loading into lung tissue by up to 40%.
Based on these research findings and known loading of cholesterol into peripheral tissue during aging and inflammation, the study team build a cholesterol dependent model for COVID19 lethality in elderly and the chronically ill.
It is found that as cholesterol increases with age and inflammation (e.g. smoking and diabetes), the cell surface is coated with viral entry points, optimally assembled viral entry proteins and optimal furin priming.
Significantly the model suggests problems arise when cholesterol levels are high in the tissue, not the blood. In fact, rapidly dropping cholesterol in the blood may indicate severe loading of cholesterol in peripheral tissue and a dangerous situation for escalated SARS-CoV-2 infectivity.
Molecules that remove cholesterol from tissue or disrupt ACE2 localization with viral entry points or furin localization for priming in the producer cells, likely reduce the severity of COVID19 in critically ill patients.
Polyunsaturated fatty acids (PUFAs) oppose the effects of cholesterol and may provide a molecular basis for eating healthy diets to avoid severe ca
ses of COVID-19.
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