NMDA Receptor Modulation in COVID-19-Associated Acute Respiratory Syndrome in both In Silico and In Vitro Approach.

ABSTRACT

The normal function of the N-methyl D-aspartate receptors (NMDAR) in human lungs depends on precisely regulated synaptic glutamate levels. Pathophysiology of the lungs is brought on by the changes in homeostasis of glutamate in the synapsis that leads to abnormal NMDAR activity. Severe acute respiratory syndrome (SARS) primarily results in lung infections, particularly lung muscle stiffening, and NMDA receptor potentiation may increase calcium ion influx and support downstream signaling mechanisms. Hence, NMDAR modulators that depend on glutamate levels could be therapeutically useful medications with fewer unintended side effects. A compound called THP (tetrahydropalmatine) that amplifies Ca2+ influx and potentiates NMDA receptors has been identified in the current study. In asthmatic human airway smooth muscle (HASM) cells, THP regulates the NMDA receptor and helps in asthmatic ASM contraction, and the pharmacological stimulation of ASM depends on both brain and respiratory NMDA receptors. Glutamate potency is altered by this substance without any voltage-dependent side effects. Additionally, a GGPP (geranylgeranyl pyrophosphate)-dependent mechanism of THP reduced the production of pro-inflammatory cytokines in ASM. THP is distinctive in terms of its chemical makeup, functioning, and agonist concentration-dependent and allosteric modulatory activity. To treat COVID-19-related SARS, THP, or any future-related compounds will make good drug-like molecule candidates.