Inhibition of measles virus infections in cell cultures by peptide-conjugated morpholino oligomers.
Measles virus (MeV) is a highly contagious human pathogen. Despite the success of measles vaccination programs, measles is still responsible for an estimated 245,000 deaths each year. There are currently no antiviral compounds available for the treatment of measles. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are antisense compounds that enter cells readily and can interfere with mRNA function by steric blocking. A panel of PPMO was designed to target various sequences of MeV RNA that are known to be important for viral replication. Five PPMO, targeting MeV genomic RNA or mRNA, inhibited the replication of MeV, in a dose-responsive and sequence-specific manner in cultured cells. One of the highly active PPMO (PPMO 454), targeting a conserved sequence in the translation start site of the mRNA coding for the nucleocapsid protein, inhibited multiple genotypes of MeV. This report provides evidence that PPMO treatment represents a promising approach for developing antiviral agents against measles and other paramyxoviruses.
Sleeman
Katrina
K
Measles, Mumps, Rubella, and Herpesviruses Laboratory Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Stein
David A
DA
Tamin
Azaibi
A
Reddish
Michael
M
Iversen
Patrick L
PL
Rota
Paul A
PA
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D008459:Measles virus / Q000187:drug effects* / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology*; D060172:Morpholinos; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D012367:RNA, Viral / Q000187:drug effects; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009025:Morpholines; D060172:Morpholinos; D010455:Peptides; D012333:RNA, Messenger; D012367:RNA, Viral