Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the betacoronavirus (β-CoVs) family. It causes severe respiratory distress with a high mortality rate in humans.12−14 Recently, a closely related novel coronavirus, coronavirus disease 2019 (COVID-19), caused an outbreak of pneumonia in Wuhan, which further underscored the risk of CoVs to the global public health.15,16 However, there is no effective treatment for CoVs. Thus, there is an urgent need to develop new antiviral agents against CoVs.14,17 MERS-CoV packages its genome in a nucleocapsid (N) protein and forms a ribonucleoprotein (RNP) complex. The RNP is essential for viral transcription and assembly. Several studies suggested that the modulation of CoV N protein oligomerization by small molecules is a feasible antiviral drug development strategy.18,19 The CoV N protein is organized into the N-terminal domain (NTD) and the C-terminal domain (CTD), with both domains participating in RNA binding.20,21 All CoV N-NTD structures are folded in a monomeric conformation. In contrast, the CoV N-CTDs are always dimeric and are responsible for N protein oligomerization via protein–protein interactions.22,23