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