Boron Clusters Versus Adamantane: A Comparative Study of Inorganic and Organic Scaffolds Against Resistant Influenza A

A series of adamantane-based amino acid derivatives incorporating γ-aminobutyric acid (GABA) as a spacer, with the general structure Ad-CH₂-CO-GABA-X-OMe (where X represents L-tryptophan (Trp), L-histidine (His), H-Ala-((S)-2-oxopyrrolidin-3-yl)-OMe (Pld), or L-methionine (Met)), were synthesized and evaluated in vitro for their antiviral activity against rimantadine-resistant influenza A virus strains A/Moscow/78/2020(H1N1)pdm09 and A/Cheboksary/125/2020(H1N1)pdm09. The results demonstrated that the presence of an L-tryptophan residue is crucial for effective inhibition of influenza virus replication, with the corresponding derivative exhibiting potent activity at an IC50 of 0.5 µg/mL. A comparative analysis of structural features and antiviral properties was conducted between the adamantane derivatives and analogous derivatives of the closo-decaborate anion ([B₁₀H₁₀]^2-) functionalized with identical amino acid residues Na₂[B₁₀H₉-O(CH₂)₂O(CH₂)₃C(O)-X-OCH₃] (X = Trp, His) and spacers of comparable length. This study suggests that combining adamantane-based compounds with closo-decaborate clusters could lead to the development of highly effective therapeutic compositions with enhanced efficacy and improved safety profiles.