  A significant subset of patients infected by SARS-CoV-2 presents olfactory,
taste, and/or chemesthesis (OTC) disorders (OTCD). These patients recover
rapidly, eliminating damage of sensory nerves. Discovering that S protein
contains two ankyrin repeat binding motifs (S-ARBMs) and some TRP cation
channels, implicated in OTC, have ankyrin repeat domains (TRPs-ARDs), I
hypothesized that interaction of S-ARBMs and TRPs-ARDs could dysregulate the
function of the latter and thus explains OTCD. Of note, some TRPs-ARDs are
expressed in the olfactory epithelium, taste buds, trigeminal neurons in the
oronasal cavity and vagal neurons in the trachea/lungs. Furthermore, this
hypothesis is supported by studies that have shown: (i) respiratory viruses
interact with TRPA1 and TRPV1 on sensory nerves and epithelial cells in the
airways, (ii) the respiratory pathophysiology in COVID-19 patients is similar
to lungs injuries produced by the sensitization of TRPV1 and TRPV4, and (iii)
resolvin D1 and D2 shown to reduce SARS-CoV-2-induced inflammation, directly
inhibit TRPA1, TRPV1, TRPV3 and TRPV4. Herein, results of blind dockings of
S-ARBMs, 408-RQIAPG-413 (in RBD but distal from the ACE-2 binding region) and
905-RFNGIG-910 (in HR1), into TRPA1, TRPV1 and TRPV4 suggest that S-ARBMs
interact with ankyrin repeat 6 of TRPA1 near an active site, and ankyrin repeat
3-4 of TRPV1 near cysteine 258 supposed to be implicated in the formation of
inter-subunits disulfide bond. These findings suggest that S-ARBMs affect
TRPA1, TRPV1 and TRPV4 function by interfering with channel assembly and
trafficking. After an experimental confirmation of these interactions, among
possible preventive treatments against COVID-19, the use of pharmacological
manipulation (probably inhibition) of TRPs-ARDs to control or mitigate
sustained pro-inflammatory response.
