The in vitro and in vivo antiviral effects of IGF1R inhibitors against respiratory syncytial virus infection

Abstract

The insulin-like growth factor 1 receptor (IGF1R) was recognized as a pivotal receptor that facilitated the cellular entry of RSV. Small molecule inhibitors designed to target IGF1R exhibited potential as potent antiviral agents. Through virtual screening, we conducted a screening process involving small molecule compounds derived from natural products, aiming to target the IGF1R protein against respiratory syncytial virus infection. The molecular dynamics simulation analysis showed that tannic acid and daptomycin interacted with the IGF1R. The experimental results in vivo and in vitro showed that tannic acid and daptomycin had anti-RSV infection potential through reducing viral loads, inflammation, airway resistance and protecting alveolar integrity. The CC50 values of tannic acid and daptomycin were 6 nM and 0.45 μM, respectively. Novel small-molecule inhibitors targeting the IGF1R, tannic acid and daptomycin, may be effective anti-RSV therapy agents. This study may in future broaden the arsenal of therapeutics for use against RSV infection and lead to more effective care against the virus.

Communicated by Ramaswamy H. Sarma

GRAPHIC ABSTRACT

RSV facilitated cellular signal transduction through fusion with IGF1R, and the inhibition of IGF1R was beneficial to inhibit RSV infection. Thus, new small-molecule inhibitors targeting the IGF1R may be effective anti-viral therapy agents.

Keywords:

• respiratory syncytial virus (RSV)
• IGF1R
• small-molecule inhibitors
• anti-RSV therapy
• structure-based virtual screening

Acknowledgements

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval and consent to participate

The study was approved by the Institutional Ethic Committee of School of Basic Medical Science, Central South University (No: 2021-KT64).

Competing interest

The authors declare that they have no competing interests

Authors’ contributions

PD and PR made same contribution. YT designed this work. PD and PR wrote the paper. PD, PR, YM, ZT and HH carried out the experiments. GW analyzed the data. All authors read and approved the final manuscript.

Availability of data and materials

The data are available from the corresponding author on any reasonable request.