Analysis of Interaction between odorant receptors and flexible spike of SARS CoV-2- key to loss of smell.

The vaccine development for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily focused on structure of the spike (S) protein. The heavy glycosylation of S with flexible hinges at stalk shields from antibodies. The flexible nature of hinges may be one of the important factors which are responsible for binding the odorant receptor of those neurons which are responsible for the loss of smell in patients with COVID-19 infection. In this study strong and stable bond formation results from reaction between R:14: Trp and Phe at the residue, the expected outcome of this research may help in designing a novel vaccine that targets the flexible hinges of SARS-CoV-2. The difference in the conformational structure of S protein and their binding with the odorant receptor in COVID-19 are prime factor for the loss of smell and taste in patients supported by the concept of Antigen (epitope) Antibody interaction by stable formation of Hydrogen bond among odorant receptor and the S protein. The flexibility of structural proteins determines if the antibodies or other defense proteins produced are homologous participating in antigen antibody reaction thus maintaining the most neutralization sensitive epitope to produce the new vaccine strain or in isolating most effectively neutralizing human mABs. Molecular and atomic level details potentiate the design and screening of small molecules that can inhibit the fusion at entry level or at odorant receptors and potentially be used in prevention and treatment of infection particularly when formulated as nasal drops, paving a new approach for pharmacologist in treatment of COVID-19 infection.

Ectopic Odorant Receptor Responding to Flavor Compounds: Versatile Roles in Health and Disease.

Prompted by the ground-breaking discovery of the rodent odorant receptor (OR) gene family within the olfactory epithelium nearly 30 years ago, followed by that of OR genes in cells of the mammalian germ line, and potentiated by the identification of ORs throughout the body, our appreciation for ORs as general chemoreceptors responding to odorant compounds in the regulation of physiological or pathophysiological processes continues to expand. Ectopic ORs are now activated by a diversity of flavor compounds and are involved in diverse physiological phenomena varying from adipogenesis to myogenesis to hepatic lipid accumulation to serotonin secretion. In this review, we outline the key biological functions of the ectopic ORs responding to flavor compounds and the underlying molecular mechanisms. We also discuss research opportunities for utilizing ectopic ORs as therapeutic strategies in the treatment of human disease as well as challenges to be overcome in the future. The recognition of the potent function, signaling pathway, and pharmacology of ectopic ORs in diverse tissues and cell types, coupled with the fact that they belong to G protein-coupled receptors, a highly druggable protein family, unequivocally highlight the potential of ectopic ORs responding to flavor compounds, especially food-derived odorant compounds, as a promising therapeutic strategy for various diseases.