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

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 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

Keywords:

• Bitter taste receptors
• α-gustducin
• bitter sensitization
• soluble angiotensin-converting enzyme receptor-2
• spike 1 protein
• Wuhan-SARS-CoV-2
• delta variant

Disclosure statement

No potential conflict of interest was reported by the authors.

Author’s contributions

S.A.K. proposed and deployed this research study, and reviewed the reprint data with necessary revisions, and prepared the reprint draft. N.D. performed the protein-protein simulations and generated the simulation data with necessary improvisations of the reprint draft. S.K.C. performed the protein-protein docking and generated the docking data, including simulation figures and data table for the reprint draft with notable feedback to ameliorate the reprint draft.

Additional information

Funding

The study hasn’t received any financial aid or grants from the government/professional bodies worldwide. However, the study was conducted with the support of our concern conferring all essential software and computational tools for generating all data and figures proposed for this research study.