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‐CH 2 ‐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 ([B 10 H 10 ] 2– ) functionalized with identical amino acid residues Na 2 [B 10 H 9 –O(CH 2 ) 2 O(CH 2 ) 3 C(O)–X–OCH 3 ] (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.