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

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS(2023)

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Abstract
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)/delta-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 delta 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 delta 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 alpha-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. [GRAPHICS]
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Key words
Bitter taste receptors,alpha-gustducin,bitter sensitization,soluble angiotensin-converting enzyme receptor-2,spike 1 protein,Wuhan-SARS-CoV-2,delta variant
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