Bitter taste receptors establish a stable binding affinity with the SARS-CoV-2-spike 1 protein akin to ACE2.

COVID-19 is caused by the highly contagious SARS-CoV-2 virus, which originated in Wuhan, China, resulting in the highest worldwide mortality rate. Gustatory dysfunction is common among individuals infected with the Wild-type Wuhan strain. However, there are no reported cases of gustatory dysfunction among patients infected with the mutant delta variant. The reason behind this remains elusive to date. This in-silico -based study aims to unravel this clinical factor by evaluating the overall binding affinity of predominant bitter taste receptors associated with gustatory function ( T2R-4 , 10 , 14 , 19 , 31 , 38 , 43 , and 46 ) with the Receptor Binding Domain ( RBD ) of spike 1 ( S1 ) protein of Wuhan ( Wild )/d elta-SARS-CoV-2 ( mut1 - T478K ; mut2 - E484K ) variants. Based on docking and MM/PBSA free binding energy scores, the Wild RBD showed a stronger interaction with T2R-46 compared to the ACE2 protein. However, both d elta variant mutants ( mut1 and mut2 ) could not establish a stronger binding affinity with bitter taste receptor proteins, except for T2R-43 against mut1 . In conclusion, the delta variants could not establish a better binding affinity with bitter taste receptors, contradicting the Wild variant that determines the severity of gustatory dysfunction among patients exposed to the d elta and Wild SARS-CoV-2 variants. The study's inference also proposes T2R-46 as an alternate binding receptor target for RBD-S1 of Wild SARS-CoV-2 , augmenting its virulence in all functional organs with compromised α-gustducin interaction and bitter sensitization. This in-silico -based study needs further wet-lab-based validation for a better understanding of the role of T2R-46 -based viral entry in the human host.Communicated by Ramaswamy H. Sarma.