Computational And Mathematical Methods In Medicine, cilt.2022, sa.9444502, ss.1-21, 2022 (SCI-Expanded)
The human angiotensin-converting enzyme 2 (hACE2) receptor is the
primary receptor for SARS-CoV-2 infection. However, the presence of
alternative receptors such as the transmembrane glycoprotein CD147 has
been proposed as a potential route for SARS-CoV-2 infection. The
outcomes of SARS-CoV-2 spike protein binding to receptors have been
shown to vary among individuals. Additionally, some patients infected
with SARS-CoV-2 develop autoimmune responses. Given that CD147 is
involved in the hyperactivation of memory T cells resulting in
autoimmunity, we investigated the interaction of the SARS-CoV-2 viral
spike protein with CD147 receptor and retinal specific CD147 Ig0 domain
in silico using molecular docking and molecular dynamics (MD)
simulations. The results indicated that binding involves two critical
residues Lys63 and Asp65 in a ubiquitous CD147 isoform, potentially
leading to the hyperactivation of T cells for only SARS-CoV-2, but not
for SARS-CoV or MERS-CoV. Overall binding was confirmed by docking
simulations. Next, MD analyses were completed to verify the docking
poses. Polar interactions suggested that the interaction via Lys63 and
Asp65 might be one of the determinants associated with severe COVID-19
outcomes. Neither did SARS-CoV nor MERS-CoV bind to these two critical
residues when molecular docking analyses were performed. Interestingly,
SARS-CoV was able to bind to CD147 with a lower affinity (-4.5 kcal/mol)
than SARS-CoV-2 (-5.6 kcal/mol). Furthermore, Delta and Omicron
variants of SARS-CoV-2 did not affect the polar interactions with Lys63
and Asp65 in CD147. This study further strengthens the link between
SARS-CoV-2 infection and autoimmune responses and provides novel
insights for prudent antiviral drug designs for COVID-19 treatment that
have implications in the prevention of T cell hyperactivation.