SARS-CoV-2-IN-28 disodium is a two-armed diphosphate ester with C7 alkyl and molecular tweezers with extended length. SARS-CoV-2-IN-28 disodium exhibits antiviral activity with IC 50 s of 0.4 μM and 1.0 μM against SARS-CoV-2 activity and the spike pseudoparticle transduction, respectively. SARS-CoV-2-IN-28 disodium induces liposomal membrane disruption with an EC 50 value of 4.4 μM.