| Autor: |
Sukumaran SY; Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia., Herrscher C; Unité Mixte Processus Infectieux en Milieu Insulaire Tropical, Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, Plateforme Technologique CYROI, Sainte Clotilde 94791, France., Rasol NE; Atta-ur-Rahman Institute for Natural Product Discovery, Level 9 FF3, Universiti Teknologi MARA Puncak Alam Campus, Bandar Puncak Alam 42300, Malaysia., Othman MA; Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia., Liew SY; Chemistry Division, Centre for Foundation Studies in Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia., Ismail NH; Atta-ur-Rahman Institute for Natural Product Discovery, Level 9 FF3, Universiti Teknologi MARA Puncak Alam Campus, Bandar Puncak Alam 42300, Malaysia., Séron K; Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-Center for Infection and Immunity of Lille (CIIL), Lille F-59000, France., Litaudon M; Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, Université Paris-Saclay, Gif-sur-Yvette 91198, France., Awang K; Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia., El Kalamouni C; Unité Mixte Processus Infectieux en Milieu Insulaire Tropical, Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, Plateforme Technologique CYROI, Sainte Clotilde 94791, France., Apel C; Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, Université Paris-Saclay, Gif-sur-Yvette 91198, France., Zahari A; Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia. |
| Abstrakt: |
In the search of new inhibitors for human coronavirus (HCoV), we screened extracts of endemic Annonaceae plants on an assay using a cellular model of Huh-7 cells infected with the human alphacoronavirus HCoV-229E. The EtOAc bark extract of the rare Southeast Asian plant Neo-uvaria foetida exhibited inhibition of HCoV-229E and SARS-CoV-2 viruses with IC 50 values of 3.8 and 7.8 μg/mL, respectively. Using LC-MS/MS and molecular networking analysis guided isolation, we discovered two new labdane-type diterpenoids, 8- epi -acuminolide ( 1 ) and foetidalabdane A ( 4 ), and three known labdane diterpenoids, acuminolide ( 2 ), 17- O -acetylacuminolide ( 3 ), and spiroacuminolide ( 5 ). A new norlabdane diterpene, 16-foetinorlabdoic acid ( 6 ), was also isolated and identified. Excluding compounds 5 and 6 , all other metabolites were active against the virus HCoV-229E. Terpenoids 1 and 4 presented antiviral activity against SARS-CoV-2 with IC 50 values of 63.3 and 93.5 μM, respectively, indicating lower potency. Additionally, virological assays demonstrated that compounds 1 , 2 , and 3 exert antiviral effects against Zika virus by specifically interfering with the late stage of its infectious cycle with IC 50 values of 76.0, 31.9, and 14.9 μM, respectively. |
