Influenza A viruses (IAVs) are negative-sense, single-stranded, segmented RNA viruses from the Orthomyxoviridae family. Moreover, Influenza A viruses cause respiratory infections that range from asymptomatic to deadly. Furthermore, Influenza A viruses (IAVs) cause seasonal flu and occasionally pandemics. In this study, researchers report the identification of CBS1117. In particular, CBS1117 is an Influenza A viruses entry inhibitor.

The therapeutics against Influenza A viruses target two viral proteins-neuraminidase (NA) and M2 ion-channel protein. Neuraminidase (Sialidase) enzymes are glycoside hydrolase enzymes that cleave (cut) the glycosidic linkages of neuraminic acids. The best-known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread of influenza infection. The viral neuraminidases are frequently used as antigenic determinants found on the surface of the influenza virus. In addition, the M2 protein is a proton-selective viroporin, integral in the viral envelope of the Influenza A virus. Proton conductance by the M2 protein in Influenza A is essential for viral replication.

CBS1117 for Hemagglutinin

As one of the viral surface glycoproteins, hemagglutinin (HA) mediates critical virus entry steps including virus binding to host cells and virus-host membrane fusion, which makes it a potential target for anti-influenza drug development. Ideally, hemagglutinin is a Class I Fusion Protein, having multifunctional activity as both an attachment factor and membrane fusion protein. Especially, CBS1117 has a 50% inhibitory concentration of 70 nM and a selectivity index of ~4000 against A/Puerto Rico/8/34 (H1N1) infection in the human lung epithelial cell line (A549). Particularly, CBS1117 exhibits potency with an IC50 value of 0.07 μM, little toxicity with a CC50 value of 274.3 μM. As a result, CBS1117 represents a promising lead compound for further drug development.

To summarise, CBS1117 is an entry inhibitor targeting group 1 Influenza A virus.

Hussein AFA, et al. Identification of entry inhibitors with 4-aminopiperidine scaffold targeting group 1 Influenza A virus. Antiviral Res. 2020 May;177:104782.