**Yi Ding, Xiaojing Zhu, Liling Hao, Mengyao Zhao, Qiang Hua and Faliang An \***

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; zjzsdy@163.com (Y.D.); 13761041863@163.com (X.Z.); holiday\_hao1988@126.com (L.H.); myzhao@ecust.edu.cn (M.Z.); qhua@ecust.edu.cn (Q.H.) **\*** Correspondence: flan2016@ecust.edu.cn; Tel.: +86-21-6425-1185

Received: 3 June 2020; Accepted: 25 June 2020; Published: 28 June 2020

**Abstract:** Four new indolyl diketopiperazines, aspamides A–E (**1**–**4**) and two new diketopiperazines, aspamides F–G (**5–6**), along with 11 known diketopiperazines and intermediates were isolated from the solid culture of *Aspergillus versicolor*, which is an endophyte with the sea crab (*Chiromantes haematocheir*). Further chiral high-performance liquid chromatography resolution gave enantiomers (+)- and (−)-**4**, respectively. The structures and absolute configurations of compounds **1**–**6** were determined by the comprehensive analyses of nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) calculation. All isolated compounds were selected for the virtual screening on the coronavirus 3-chymoretpsin-like protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the docking scores of compounds **1**–**2**, **5**, **6**, **8** and **17** were top among all screened molecules, may be helpful in fighting with Corona Virus Disease-19 (COVID-19) after further studies.

**Keywords:** endophyte fungus; *Aspergillus versicolor*; diketopiperazines; ECD calculation; enantiomers
