Urtica dioica agglutinin (UDA) as a potential candidate for inhibition of SARS-CoV-2 Omicron variants: In silico prediction and experimental validation.

BACKGROUND

The high number of mutations and consequent structure modifications in a Receptor-Binding Domain (RBD) of the spike protein of the Omicron variant of SARS-CoV-2 increased concerns about evading neutralization by antibodies induced by previous infection or vaccination. Thus, developing novel drugs with potent inhibitory activity can be considered an alternative for treating this highly transmissible variant. Considering that Urtica dioica agglutinin (UDA) displays antiviral activity against SARS-CoV-2, the potency of this lectin to inhibit the Receptor Binding Domain of the Omicron variant (RBD) was examined in this study.

PURPOSE

This study examines how UDA inhibits the Omicron variant of SARS-CoV-2 by blocking its RBD, using a combination of in silico and experimental methods.

METHODS

To investigate the interaction between UDA and RBD, the CLUSPRO 2.0 web server was used to dock the RBD-UDA complex, and molecular dynamics simulations were performed by the Gromacs 2020.2 software to confirm the stability of the selected docked complex. Finally, the binding affinity (ΔG) of the simulation was calculated using MM-PBSA. In addition, ELISA and Western blot tests were used to examine UDA's binding to RBD.

RESULTS

Based on the docking results, UDA forms five hydrogen bonds with the RBD active site, which contains mutated residues Tyr501, Arg498, Arg493, and His505. According to MD simulations, the UDA-RBD complex is stable over 100 ns, and its average binding energy during the simulation is -87.201 kJ/mol. Also, the ELISA test showed that UDA significantly binds to RBD, and by increasing the concentration of UDA protein, the attachment to RBD became stronger. In Western blotting, RBD was able to attach to and detect UDA.

CONCLUSION

This study indicates that UDA interaction with RBD prevents virus attachment to Angiotensin-converting enzyme 2 (ACE2) and, therefore, its entry into the host cell. Altogether, UDA exhibited a significant suppression effect on the Omicron variant and can be considered a new candidate to improve protection against severe infection of this variant.