病毒学：当前研究

Investigation of Cepharanthine Binding with Viral Proteins Reveal its Potential Targets against Coronavirus

Abstract

Donghui Huo, Wenlin An, Huan Xu, Aixia Yan and Yigang Tong

The outbreak of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 is becoming a worldwide problem. We previously reported that cepharanthine (CEP) demonstrated strong anti-coronavirus effects, however, the mechanism underlying CEP’s anti-coronavirus effects remains unknown. We herein performed Surface Plasmon Resonance (SPR) to investigate the biological influence of CEP on different proteins of SARS-CoV-2. Meanwhile, molecular docking study was used to screen the potential binding sites of CEP on the virus. The binding of CEP to the nsp13 helicase with a Kd of 3.806*10-6 M shows that helicase is a relatively strong possible target of CEP. Besides, CEP could bind to the viral main proteinase (3CLpro) that contributes to the intervention of polypeptide cleavage. We also compared the potential binding pockets and binding affinity on viral spike proteins (S1 and S2 subunits) at both open and closed states. Our study revealed that CEP exerts its anti-coronavirus effects at viral genomic RNA replication, transcription, translation and viral invasion levels, providing a theoretical basis for the development of CEP as a promising anti-coronavirus drug.