TEMPO.CO, Jakarta – New developments regarding drugs and links to the corona virus were obtained by scientists in the United States. Researchers from UC San Diego Health recently reported that statins or drugs cholesterol-lowering associated with a reduced risk of developing severe Covid-19 disease and a faster recovery time.
Meanwhile, a second research team at UC San Diego School of Medicine has also found evidence that helps explain this. In short, removing cholesterol from cell membranes prevents entry corona virus.
The clinical study, published in mid-September 2020 in the American Journal of Cardiology, was led by Lori Daniels, Professor and Director of the Cardiovascular Intensive Care Unit at UC Diego.
His mechanistic study was published three days later in The EMBO Journal, led by Tariq Rana, professor and Head of the Division of Genetics in the Department of Pediatrics at UC San Diego of Medicine and Moores Cancer Center. Patients with Covid-19 who were on statins fared better.
A molecule known as ACE2 is like a doorknob on the outer surface of many human cells, where it helps regulate and lower blood pressure. ACE2 can be affected by statins and other drugs for cardiovascular disease.
However, in January 2020, researchers discovered a new role for ACE2, which is used by the SARS-CoV-2 virus as a receptor to enter lung cells and form respiratory infections.
“When faced with this new virus at the start of the pandemic, there was a lot of speculation around certain drugs that affect ACE2, including statins and whether it could affect risk. Covid-19, “said Daniels, as quoted MedicalXpress.
He continued to need further confirmation whether statin use would impact the severity of the corona virus infection and determine it was safe for patients to continue treatment. To do this, he and his team retrospectively analyzed the electronic medical records of 170 coronavirus positive patients and 5,281 Covid negative control patients admitted to UC San Diego Health between February and June 2020.
They collected anonymous data that included patient data, disease severity, length of stay in hospital, outcome, and use of the ACE enzyme, and angiotensin II inhibitor (ARB) approximately one month prior to admission. Among patients with Covid-19, 27 percent were actively taking statins at admission, while 21 percent were on ACE inhibitors and 12 percent were on ARBs. The average length of stay in the hospital was 9.7 days for Covid-19 patients.
Researchers found statin use prior to hospital admission for COVID-19 was associated with a more than 50 percent reduced risk of developing severe COVID-19, compared with those with COVID-19 but not taking statins.
“We found statins are not only safe but also have the potential to protect against severe COVID-19 infection. Statins in particular can inhibit SARS-CoV-2 infection through their anti-inflammatory effects and binding abilities that have the potential to stop the development of the virus,” he said.
This initial study was relatively small and focused on one health system. Going forward, Daniels is partnering with the American Heart Association to analyze thousands of patients across the country to corroborate the data he developed locally.
Draining cholesterol from cell membranes blocks the entry of the corona virus. Statins were not yet on the radar when researchers started the EMBO Journal study about six months ago. Initially, the team just wanted to see which genes were active in human lung cells in response to SARS-CoV-2 infection.
A gene called CH25H is reported to be very hot. The gene encodes an enzyme that converts cholesterol.
“I’m excited because with HIV, Zika, and a few others, we know that CH25H blocks the ability of the virus to enter human cells,” said Rana.
The enzymatic activity of CH25H produces a modified form of cholesterol called 25-hydroxycholesterol (25HC). In turn, this activates another enzyme called ACAT, which is found inside cells in the endoplasmic reticulum.
ACAT then depletes the accessible cholesterol on the cell membrane. This is a normally occurring process that starts at high speed during multiple viral infections.
The team quickly got to work examining the 25HC in the context of SARS-CoV-2 from several angles. They explored what happens to human lung cells in the laboratory with and without 25HC treatment. No matter where it comes from, adding 25HC inhibits the virus’s ability to enter cells.
“The differences between untreated and treated cells with 25HC are like night and day,” he said.
While the coronavirus uses the ACE2 receptor to initially anchor in cells, Rana’s research suggests that the virus also needs cholesterol to combine and enter cells.
This is where the role of 25HC is to remove a lot of membrane cholesterol so as to prevent the entry of viruses. Statins may also have a similar effect in the same way. As a result, the corona virus cannot enter.
Rana said this has happened in the body regularly. So maybe the body just needs to boost it with a statin or some other means, to make it more resistant to some viruses.
“This is no different from cancer immunotherapy, the idea that sometimes instead of attacking the tumor directly, it is better to arm the patient’s immune system to do a better job of clearing the tumor by itself,” he said.
If it can be developed into a therapy, 25HC may work better as an antiviral than a statin. This is because it works specifically on cholesterol in cell membranes, not cholesterol throughout the body.
Like all drugs, statins can cause negative side effects, including digestive problems and muscle aches, and may not be an option for many people with Covid-19. What’s more, some previous research suggested statins can also increase ACE2 levels, allowing more virus entry. This was not the case at 25HC.
However, statins are FDA approved for human use, while 25HC is a natural product currently only available for lab work. The researchers plan to continue to optimize 25HC as a potential antiviral.
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