Structure-based Assessment of Homologous Analogues of NAtural products -SAHANA: A novel approach to screen bioactive compounds in comparison with their synthetic drug counterparts

Abstract Background The present study describes a novel strategy to screen natural products (NPs) for their therapeutic effects with predicted most-probable mode of action. The method entitled ‘Structure-based Assessment of Homologous Analogues of NAtural products-SAHANA’ follows a strategy to compare natural products against synthetic drugs based on their molecular properties and 2-dimensional structural similarities. The method is based on a well-established hypothesis that, the molecules with similar structural properties will have similar functions.Methods The method was validated by implementing it for the screening of NPs against different disease conditions. The biological effect of the identified NPs were evaluated based on their binding affinity with the target of their synthetic drug counterpart, prior to which, their in-silico pharmacokinetic and pharmacodynamics properties were assessed. The stability of binding was validated using molecular dynamics simulation studies.Results The study yielded NPs with significant structural similarities to synthetic drugs and binding interactions stabilizing the macromolecular structures.Conclusions The results envisage a strong indication that the natural product drugs can work in a manner similar to that of synthetic drugs if administered individually. Further, the results encourage the application of the current strategy to screen competent drugs against any disease condition ad libitum.