Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs

Ono, T.; Kamada, K.; Hayashi, R.; Piacenti, A. R.; Gabutt, C.; Sriwilaijaroen, N.; Hiramatsu, H.; Kanai, Y.; Inoue, K.; Nakakita, S.-i.; Kawahara, T.; Ie, Y.; Watanabe, Y.; Suzuki, Y.; Contera, S.; Matsumoto, K.

doi:10.1101/2020.03.18.996884

bioRxiv · 10.1101/2020.03.18.996884

Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs

Ono, T.·Kamada, K.·Hayashi, R.·Piacenti, A. R.·Gabutt, C.·Sriwilaijaroen, N.·Hiramatsu, H.·Kanai, Y.·Inoue, K.·Nakakita, S.-i.·Kawahara, T.·Ie, Y.·Watanabe, Y.·Suzuki, Y.·Contera, S.·Matsumoto, K.

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Abstract

Small solid-state devices are candidates for accelerating biomedical assays/drug discovery, however their potential remains unfulfilled. Here, we demonstrate that graphene-field effect transistors (FET) can be used to successfully detect the key molecular events underlying viral infections and the effect of antiviral drugs. Our device success is achieved by bio-mimicking the host-cell surface during an influenza infection at the graphene channel. In-situ AFM confirms the biological interactions at the sialic acid-functionalized graphene: viral hemagglutinin (HA) binds to sialic acid, and neuraminidase (NA) reacts with the sialic acid-HA complex. The graphene-FET detects HA binding to sialic acid, and NA cleavage of sialic acid. The inhibitory effect of the drug "zanamivir" on NA-sialic acid interactions is monitored in real-time; the reaction rate constant of NA-sialic acid reaction was successfully determined. We demonstrate that graphene-FETs are powerful platforms for measurement of biomolecular interactions and contribute to future deployment of solid-state devices in drug discovery/biosensing.

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Ono, T., Kamada, K., Hayashi, R., Piacenti, A. R., Gabutt, C., Sriwilaijaroen, N., Hiramatsu, H., Kanai, Y., Inoue, K., Nakakita, S.-i., Kawahara, T., Ie, Y., Watanabe, Y., Suzuki, Y., Contera, S., Matsumoto, K.. 2020-03-20. Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs. https://doi.org/10.1101/2020.03.18.996884

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