Coronavirus uses cholesterol receptor to penetrate human cells, scientists say

TASS Russian News Agency | Nov 26, 2020 at 3:05 PM

TASS, November 26. Molecular biologists from China have discovered first evidence of the fact that the coronavirus penetrates human cells not only by using the "lung" ACE2 receptor but also the SR-B1 receptors which recognize cholesterol molecules. Their findings were published in the Nature Metabolism journal.

"Commonalities between SARS-CoV-2 and SARS-CoV infection suggest that antibodies, peptides and small compounds targeting ACE2 can be used in the treatment of SARS-CoV-2. Identifying SR-B1 as a SARS-CoV-2 entry cofactor, we propose that drugs that target SR-B1 could act as antivirals that limit SARS-CoV-2 infection. As a proof of concept, we have shown that ITX 5601, a clinically approved inhibitor of HCV infection, strongly inhibits SARS-CoV-2 infection of cultured cells," the scientists wrote.

The SARS-CoV-2 virus penetrates lung cells of humans and other mammals, using the ACE2 protein molecules covering their surface. These growths, as the scientists have known for a while, play an important part in the vital functions of SARS, the atypical pneumonia agent. Later biologists discovered that the coronavirus may also use another receptor, CD147, linked to the functioning of immune cells.

The ability of the COVID-19 agent to adhere to several different receptors at once made the scientists study actively to which other types of protein molecules the coronavirus may bind and how this affects the course of the disease.

A group of Chinese molecular biologists led by Zhang Rui, researcher at the Liaoning Cancer Hospital and Institute in Shenyang, China, have discovered another receptor involved in the development of the coronavirus infection by studying the structure of the S-protein of the coronavirus, the part of its membrane which directly binds with ACE2.

A new "accomplice" of the coronavirus

The scientists have known for a while that only a small part of this protein chain is involved in attachment of the virus to a receptor which indicates possible other functions of the S-protein. In order to uncover them, the scientists were comparing the structure of this molecule with various human cell receptors.

This analysis uncovered that the S-protein contained amino acid sequences very similar to those responsible for the attachment of the SR-B1 receptor to cholesterol and lipoprotein molecules. Guided by this idea, the scientists checked whether the coronavirus particles can interact with these substances and with the SR-B1 receptor itself.

The subsequent experiments demonstrated that the virus indeed is capable of binding to cholesterol but not to the molecules similar to it, and also unexpectedly discovered that the same part of the S-protein that interacts with ACE2 was involved. Encountering this property of the virus, the scientists decided to see what happens if large amounts of cholesterol and lipoprotein are added to the culture medium with cells infected with the SARS-CoV-2 virus.

These experiments confirmed that cholesterol and the receptors recognizing it play an important role in the process of the virus penetrating healthy cells. The more of its molecules were present in the culture medium, the quicker SARS-CoV-2 infected new victims. At the same time, blocking SR-B1 using the ITX 5601 preparation sharply curbed the spread of the virus.

The interactions of the S-protein of the virus with the SR-B1 receptors by itself do not lead to the development of the infection, this happens only in the presence of viable ACE2 molecules on the surface of cellular membranes. This explains many strange differences in the course of the disease in different patients as well as why many medications against viral Hepatitis C, for which SR-B1 serves as the main dissemination channel, work against COVID-19.

The scientists hope that a further study of interactions between this receptor and the SARS-CoV-2 particles will aid in understanding how this property of the virus can be used in order to suppress the infection and develop the most effective methods of treating it.