SNX27-mediated endocytic recycling of GLUT1 is suppressed by SARS-CoV-2 spike, possibly explaining neuromuscular disorders in patients with COVID-19

Cytoplasmic tail determines the membrane trafficking and localization of SARS-CoV-2 spike protein

“…GLUT1 facilitated the glucose supply to the brain and other organs ( Tang and Monani, 2021 ). S protein suppressed the association between GLUT1 and SNX27, preventing its endocytic recycling in a similar way as the inhibition to ACE2 ( Ren et al, 2022a ). In the patients recovered from acute symptoms, the remaining of S protein contributed to GLUT1-deficiency, which may explain the neurological symptoms in the Long-COVID, such as seizures and persistent or paroxysmal neuromuscular disorders.…”

Deficiency of HTR4 and ADRB1 caused by SARS-CoV-2 spike may partially explain multiple COVID-19 related syndromes including depression, cognitive impairment, loss of appetite, heart failure, and hypertension

“…Previously in this Journal, we reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) blocked sorting nexin 27 (SNX27)- mediated endocytic recycling of angiotensin-converting enzyme 2 (ACE2) and glucose transporter type 1 (GLUT1) ( 1 , 2 ). By its postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ) domain, SNX27 recognizes PDZ domain binding motif (PBM) in multiple endocytic recycling membrane proteins, which are functional in cell surface ( 3 , 4 ).…”

“…In order to recycle cargoes back to plasma membrane, SNX27 associates with Vps26, a subunit of retromer composed of Vps35, Vps29 and Vps26 ( 4 ). Previously, we uncovered that SARS-CoV-2 S abrogated SNX27-Vps26A interaction ( 1 ). However, S-T1238A, a mutant losing binding affinity to SNX27, did not affect the interaction between SNX27 and Vps26A ( 1 ).…”

“…Previously, we uncovered that SARS-CoV-2 S abrogated SNX27-Vps26A interaction ( 1 ). However, S-T1238A, a mutant losing binding affinity to SNX27, did not affect the interaction between SNX27 and Vps26A ( 1 ). To examine whether SARS-CoV-2 S affects the plasma membrane localization of HTR4, we performed the confocal immunofluorescent analysis experiments.…”

Insulin may increase disease severity and mortality of COVID-19 through Na+/H+ exchanger in patients with type 1 and type 2 diabetes mellitus

“…The reduction of GLUT1 also leads to a decrease in the energy supply of cardiomyocytes. GLUT1 level was low in COVID-19 patients, especially in long COVID-19 patients, but its mechanism has not been fully explained [ 18 ]. In patients with COVID-19, the GLUT1 level may be decreased by angiotensin II-mediated suppression or due to NHE1-mediated lysosomal degradation [ 19 , 20 ].…”