Amantadine an antiviral, antiparkinsonian drug has cage like basic structure it is a colorless, crystalline compound with a camphor-like odor. The interactions of amantadine with ACE-inhibitors, cephalosporins, essential and trace elements, H1-receptor antagonists, H2-receptor antagonists, NSAIDs and quinolones was investigated in 0.1 N HCl. Amantadine complexes were synthesized with all interacting drugs and characterized by UV, FTIR, 1H-NMR and mass spectroscopy. The energy minimization study was carried out to determine the binding site of amantadine and along with these studies, metal complexes of amantadine with (Mn, Fe, Cu, Zn, Ca, Mg, Cr, Co, Ni, and Cd) were synthesized. The structures of these complexes were confirmed by IR, NMR, CHN elemental analysis and AA spectroscopy. Antiviral studies of amantadine-drug complexes evaluated through National institute of Infectious Diseases, USA in Southern Research Institute Maryland, USA. Against Biodefence viruses (Rift Valley Fever, Tacaribe, VEE, Yellow Fever), Respiratory viruses ( RSV A, Adeno, PIV, Rhinovirus Type 2, RSV A, Flu A (H1N1), Flu A (H3N2), Flu A (H5N1), Flu B, SARS),Herpes viruses (HSV-1, HSV-2, HCMV, VZV, EBV).