Potential anti-respiratory syncytial virus lead compounds from Aglaia species.
Although the global prevalence of respiratory syncytial virus (RSV) infection, especially among infants and young children is on the increase, there are only limited therapeutic options for treatment of this disease. Therefore, the search for novel antiviral inhibitors of RSV has become more intensive. In a pilot screening of eighteen compounds from various Aglaia species for anti-RSV activity, we identified dammarenolic acid (ignT1), aglaiol (dupT1) and niloticin (cucT1) as potential anti-RSV compounds, with ignT1 being the most potent. Methylation of ignT1 results in a complete loss of anti-RSV activity. Time of addition studies reveal that both ignT1 and dupT1 target the RSV replication at a post-entry stage, although ignT1 was more potent. Dammarenolic acid (ignT1) was also more cytotoxic than aglaiol (dupT1). By carrying out parallel anti-RSV screening with aphidicolin (a highly cytotoxic diterpenoid) and ignT1, we showed that although aphidicolin was more cytotoxic than ignT1, it had virtually no anti-RSV activity. Therefore, dammarenolic acid, aglaiol and niloticin demonstrate potent anti-RSV activity that shouldbe explored further in the current search for anti-RSV therapeutic agents.
Esimone
C O
CO
Department of Molecular and Medical Virology, Ruhr University, Bochum. coesimone@yahoo.com
Eck
G
G
Duong
T N
TN
Uberla
K
K
Proksch
P
P
Grunwald
T
T
D031602:Aglaia / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D007700:Kinetics; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D010948:Viral Plaque Assay
D000972:Antineoplastic Agents, Phytogenic; D000998:Antiviral Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue