Comparative Assessment of the Inhibitory Potential of the Herbicide Glyphosate and Its Structural Analogs on RGD-Specific Integrins Using Enzyme-Linked Immunosorbent Assays

Transmembrane glycoprotein integrins play crucial roles in biochemical processes, and by their inhibition or activation, different signal pathways can be disrupted, leading to abnormal physiological functions. We have previously demonstrated the inhibitory effect of glyphosate herbicide's active ingredient on cell adhesion and its alpha v beta 3 integrin antagonist effect. Therefore, it appeared particularly exciting to investigate inhibition of glyphosate and its metabolites on a wider range of Arg-Gly-Asp (RGD) binding integrins, namely alpha v beta 3, alpha 5 beta 1 and alpha llb beta 3. Thus, the purpose of this study was to assess how extended the inhibitory effect observed for glyphosate on the integrin alpha v beta 3 is in terms of other RGD integrins and other structurally or metabolically related derivatives of glyphosate. Five different experimental setups using enzyme-linked immunosorbent assays were applied: (i) alpha v beta 3 binding to a synthetic polymer containing RGD; (ii) alpha v beta 3 binding to its extracellular matrix (ECM) protein, vitronectin; (iii) alpha 5 beta 1 binding to the above polymer containing RGD; (iv) alpha llb beta 3 binding to its ECM protein, fibrinogen and (v) alpha v beta 3 binding to the SARS-CoV-2 spike protein receptor binding domain. Total inhibition of alpha v beta 3 binding to RGD was detected for glyphosate and its main metabolite, aminomethylphosphonic acid (AMPA), as well as for acetylglycine on alpha 5 beta 1 binding to RGD.