Abstract
Some interactions of enveloped viruses with the host cell membrane have a cholesterol-dependent component, which may account for clinical manifestations of the infectious disease and can be used for the development of antiviral drugs. These cholesterol-dependent interactions can be mediated by cholesterol-recognition amino-acid consensus (CRAC) motifs present in viral proteins. The S protein of the SARS-CoV and SARS-CoV2 coronaviruses contains CRAC motifs that can be involved in the process of virus entry into the cell. Besides, during viral envelope formation, CRAC motifs can be responsible for binding of cell membrane cholesterol, leading to depletion of cell membrane cholesterol and subsequent malfunctioning of cellular cholesterol-dependent proteins, destabilization and permeabilization of cell membranes and, ultimately, to the death of infected cells. Understanding the mechanisms of cholesterol-dependent virus–cell interactions and the role of CRAC-containing viral proteins in the pathogenesis of the disease can serve as the basis for the development of new drugs that prevent both coronavirus entry into the cell and the damage of the infected cell during the viral morphogenesis. The target for such drugs can be the S-protein/cholesterol interface. CRAC-containing peptides derived from viral proteins may be among these agents. These peptides can also be used as experimental tools to study cholesterol-dependent virus–cell interactions.
Highlights
The COVID-19 pandemic caused by the severe respiratory syndrome (SARS)-CoV2 coronavirus has resulted in almost hundred of millions of infections and about two millions of deaths in 2020 [1, 2]
This review focuses on the fact that the coronavirus S protein, which is involved in cholesterol-dependent virus–cell interactions during entry and replication stages, contains the so-called cholesterol recognition amino-acid consensus (CRAC) motifs [16, 17] that can mediate these interactions
At a high viral load and high replication rate the reduction in the cholesterol level in the cell membranes can lead to their permeabilization and subsequent cell death, and this can be one of the factors in pathogenesis of diseases induced by SARS-CoV2
Summary
The COVID-19 pandemic caused by the SARS-CoV2 coronavirus has resulted in almost hundred of millions of infections and about two millions of deaths in 2020 [1, 2]. Some interactions of enveloped viruses with the cell in the course of penetration and during assembly, budding, and exit of the virus from the cell are known to Cholesterol Recognition Motifs (CRAC) in the S Protein of Coronavirus: A Possible Target...
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