New type of RNA virus replication inhibitor based on decahydro-closo-decaborate anion containing amino acid ester pendant group.
Varvara V AvdeevaTimur M GaraevNatalia V BreslavElena I BurtsevaTatyana V GrebennikovaAndrei P ZhdanovKonstantin Yu ZhizhinElena A MalininaNikolay T KuznetsovPublished in: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry (2022)
In this work, a synthetic approach to prepare an example of new class of the derivatives of the closo-decaborate anion with amino acids detached from the boron cluster by pendant group has been proposed and implemented. Compound Na 2 [B 10 H 9 -O(CH 2 ) 4 C(O)-His-OMe] was isolated and characterized. This compound has an inorganic hydrophobic core which is the 10-vertex boron cage and the -O(CH 2 ) 4 C(O)-His-OMe organic substituent. It has been shown to possess strong antiviral activity in vitro against modern strains of A/H1N1 virus at 10 and 5 µg/mL. The compound has been found to be non-cytotoxic up to 160 µg/mL. At the same time, the compound has been found to be inactive against SARS-CoV-2, indicating specific activity against RNA virus replication. Molecular docking of the target derivative of the closo-decaborate anion with a model of the transmembrane region of the M2 protein has been performed and the mechanism of its antiviral action is discussed.