Synthesis of 4<i>H</i>-Pyrazolo[3,4-<i>d</i>]pyrimidin-4-one Hydrazine Derivatives as a Potential Inhibitor for the Self-Assembly of TMV Particles
Ya Wang, Shengxin Guo, Wei Sun, Hong Tu, Yao Tang, Ying Xu, Renjiang Guo, Zhichao Zhao, Zhaokai Yang, Jian Wu
Abstract
Tobacco mosaic virus coat protein (TMV-CP), as a potential target for the development of antiviral agents, can assist in the long-distance movement of viruses and plays an extremely important role in virus replication and propagation. This work focuses on the synthesis and the action mechanism of novel 4 H -pyrazolo[3,4- d ] pyrimidin-4-one hydrazine derivatives. The synthesized compounds exhibited promising antiviral activity on TMV. Specifically, compound G2 exhibited high inactivating activity (93%) toward TMV, slightly better than commercial reagent NNM (90%). The action of mechanism was further explored by employed molecular docking, molecular dynamics simulation, microscale thermophoresis, qRT-PCR, and transmission electron microscopy. Results indicated that G2 had the capability to interact with amino acid residues such as Trp352, Tyr139, and Asn73 in the active pocket of TMV-CP, creating strong hydrophobic interactions and thus obstructing the virus’s self-assembly.