Close the second door
A second "door" for coronavirus was found in human cells
Polina Loseva, N+1
Chinese scientists have discovered another target for the SARS-CoV-2 coronavirus on the surface of human cells. This is the CD147 protein, which, by the way, is used not only by the previous coronavirus, the causative agent of SARS, but also by the malarial plasmodium. By blocking this protein, the researchers were able to stop the spread of the virus in cell culture. Clinical trials of the corresponding blocker drug have already begun. The work is published on the preprint portal bioRxiv (Wang et al., SARS-CoV-2 invades host cells via a novel route: CD147-spike protein).
A cure for the SARS-CoV-2 coronavirus can be sought in various ways: for example, try to prohibit it from multiplying inside cells or stimulate its own cellular defense systems. But there is another way – to block the virus from entering the cells.
The attack of the virus on the target begins with the fact that it adheres with its surface proteins to proteins on the cell membrane. Then the membrane of the virus merges with the cellular one, and the internal contents of the viral particle (RNA genome) turns out to be inside the cell. Until now, it was believed that SARS-CoV-2, like its predecessor, SARS-CoV, the causative agent of SARS, binds best to the cellular protein ACE2. However, the new coronavirus has as many as four surface proteins, so it is logical to assume that it will have several targets, that is, binding points to the cell.
Ke Wang, together with colleagues from the Fourth Military Medical University in Xi'an, described another such "door" inside the cell that SARS-CoV-2 can use. Back in 2005, after an outbreak of SARS, they noticed that SARS-CoV could bind to the CD147 receptor on the cell surface. It is a protein from the immunoglobulin family. Apparently, it has several functions: for example, it triggers the work of metalloproteinases – proteins that rearrange extracellular matter in tissues. Since the previous target, ACE2, turned out to be shared by the two viruses, they assumed that the new coronavirus would also bind to CD147.
To test this, the researchers infected a human kidney cell culture with coronavirus. Then they treated it with CD147 antibodies and measured the number of damaged cells, as well as the concentration of viral genomes in the culture medium. It turned out that with an antibody concentration of 3 micrograms / ml, it is possible to achieve an almost one hundred percent stop of the spread of the virus between cells.
Then the authors of the work showed using immunofluorescence analysis that the surface protein of coronavirus SP and CD147 are able to interact with each other. And finally, the cells infected with coronavirus were stained with antibodies to these proteins. Inside the cells, SP and CD147 appeared side by side, which confirms the assumption that CD147 can help the virus penetrate into the cells.
CD147 is a target not only for coronaviruses, but also for malaria – it is for this molecule on the surface of red blood cells that the malarial plasmodium "grabs". Therefore, the antibody-blocker CD147 has long existed in the form of several drugs. In parallel with the publication of scientific data, Chinese scientists have begun a clinical trial of these drugs to combat SARS-CoV-2. They believe that closing this "door" is more logical than the previous one. ACE2 blockade is fraught with various side effects, including for the lungs, which already suffer the most during infection. At the same time, the blockade of CD147, in their opinion, should not cause such consequences.
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