D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19

A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or / studies, the other is for identifying lead compounds against potential drug targets docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 Å on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easy to be updated, and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php). Currently, the webserver contains 42 proteins [20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release] with 69 different conformations/structures and 557 potential ligand-binding pockets in total. With 6 examples, we demonstrated that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.

Cembrane-type diterpenoids from the South China Sea soft coral

Eight cembrane-type diterpenoids, namely, (+)-(6)-6-hydroxyisosarcophytoxide (), (+)-(6)-6-acetoxyisosarcophytoxide (), (+)-17-hydroxyisosarcophytoxide (), sarcomililatins A-D (-), and sarcomililatol (), were isolated from the soft coral collected from Weizhou Island, Guangxi Autonomous Region, together with 2 known related analogues, (+)-isosarcophytoxide () and (+)-isosarcophine (). The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. The absolute configuration of compound was established by the modified Mosher׳s method, while the absolute configurations of compounds and were assigned by electronic circular dichroism (ECD) spectroscopy and that of compound was established by time-dependent density functional theory electronic circular dichroism (TD-DFT ECD) calculation. In bioassays, compound displayed significant cytotoxicity against the human cancer cell lines human promyelocytic leukemia cells (HL-60) and human lung adenocarcinoma cells (A-549) with IC values of 0.78±0.21 and 1.26±0.80 μmol/L, respectively. Compounds and also showed moderate inhibitory effects on the TNF-induced Nuclear factor kappa B (NF-B, a therapeutical target in cancer) activation, showing IC values of 35.23±12.42 and 22.52±4.44 μmol/L, respectively.