Role of cholesterol-recognition motifs in the infectivity of SARS-CoV-2 variants

BAIER, CARLOS JAVIER; BARRANTES, FRANCISCO J.

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Año: 2023 vol. 222

0927-7765

The presence of linear amino acid motifs with the capacity to recognize the neutral lipid cholesterol, known as Cholesterol Recognition/interaction Amino acid Consensus sequence (CRAC), and its inverse or mirror image, CARC, has recently been reported in the primary sequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike S homotrimeric glycoprotein. These motifs also occur in the two other pathogenic coronaviruses, SARS-CoV, and Middle-East respiratory syndrome CoV (MERS-CoV), most conspicuously in the transmembrane domain, the fusion peptide, the amino-terminal domain, and the receptor binding domain of SARS-CoV-2 S protein. Here we analyze the presence of cholesterol-recognition motifs in these key regions of the spike glycoprotein in the pathogenic CoVs. We disclose the inherent pathophysiological implications of the cholesterol motifs in the virus-host cell interactions and variant infectivity.