Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged first around December 2019 in the city of Wuhan, China. Since then, several variants of the virus have emerged with different biological properties. This pandemic has so far led to widespread infection cycles with millions of fatalities and infections globally. In the recent cycle, a new variant omicron and its three sub-variants BA.1, BA.2 and BA.3 have emerged which seems to evade host immune defences and have brisk infection rate. Particularly, BA.2 variant has shown high transmission rate over BA.1 strain in different countries including India. In the present study, we have evaluated a set of eighty drugs/compounds using in silico docking calculations in omicron and its variants. These molecules were reported previously against SARS-CoV-2. Our docking and simulation analyses suggest differences in affinity of these compounds in omicron and BA.2 compared to SARS-CoV-2. These studies show that neohesperidin, a natural flavonoid found in Citrus aurantium makes a stable interaction with spike receptor domain of omicron and BA.2 compared to other variants. Free energy binding analyses further validates that neohesperidin forms a stable complex with spike RBD in omicron and BA.2 with a binding energy of-237.9 +/- 18.7 kJ/mol and-164.1 +/- 17.5 kJ/mol respectively. Key residual differences in the RBD interface of these variants form the basis for differential interaction affinities with neohesperidin as drug binding site overlaps with RBD-human ACE2 interface. These data might be useful for the design and development of novel scaffolds and pharmacophores to develop specific therapeutic strategies against these novel variants.

Automated summary

COVID-19, caused by SARS-CoV-2, first emerged in Wuhan, China in December 2019. Since then, different variants of the virus have emerged. The recent emergence of the omicron variant and its sub-variants BA.1, BA.2, and BA.3 has shown a high infection rate and the ability to evade host immune defenses. In this study, the affinity of 80 drugs/compounds against omicron and its variants was evaluated using in silico docking calculations, and it was found that neohesperidin, a natural flavonoid, showed a stable interaction with the spike receptor domain of omicron and BA.2 compared to other variants. These findings could be important for developing specific therapeutic strategies against these novel variants.