Background:The incorporation of anti-HIV drugs into polymer to form polymer-drug
conjugates has been reported to result in improved therapeutic activity. Zidovudine, an anti-HIV
drug, was explored alone and in combination with known drug molecules using polyamidoaminebased
carriers.Objective:Polymer-drug conjugates incorporated with zidovudine, cinnamic acid, and 4-aminosalicylic
acid were prepared and evaluated for their potential efficacy in vitro against pseudo-
HIV-1.Methods:Aqueous Michael addition polymerization reaction was employed to prepare the conjugates.
The conjugates were incorporated with zidovudine, cinnamic acid, and 4-aminosalicylic
acid. They were characterized by SEM/EDX, XRD, FTIR, NMR, LC-MS, particle size analysis,
in vitro analysis, computational studies, and in silico toxicity predictions.Results:The conjugates displayed spherically shaped morphology. The in vitro findings showed
that polymer-drug conjugates, T15 and T16, with a single drug were effective against pseudo-
HIV-1 at high concentrations of 111.11 and 333.33 μg/mL, respectively. The molecular docking
studies confirmed the in vitro results. The Swiss ADME, ProTox-II, and GUSAR (General Unrestricted
Structure-Activity Relationships) revealed that these compounds are promising antiviral
compounds.Conclusion:The prepared polymer-drug conjugates with a single drug showed promising effects
against the Pseudo-HIV-1, and the conjugates displayed features that make them potential anti-
HIV therapeutics that require further studies.