title: Indomethacin has a potent antiviral activity against SARS coronavirus.
abstract: Severe acute respiratory syndrome (SARS) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (SARS-CoV). Existing in non-identified animal reservoirs, SARS-CoV continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections.
  
  
  OBJECTIVE
  Starting from the observation that cyclopentenone cyclooxygenase (COX) metabolites are active against several RNA viruses, we investigated the effect of the COX inhibitor indomethacin on coronavirus replication.
  
  
  METHODS
  Work involving infectious SARS-CoV was performed in biosafety level 3 facilities. SARS-CoV was grown in monkey VERO cells and human lung epithelial A549 cells, while canine coronavirus (CCoV) was grown in A72 canine cells. Antiviral activity was analysed by determining infective virus titres by TCID50, viral RNA synthesis by Northern blot analysis and real-time RT-PCR, and viral protein synthesis by SDS-PAGE analysis after 35S-methionine-labelling. Antiviral efficacy in vivo was determined by evaluating virus titres in CCoV-infected dogs treated orally with 1 mg/kg body weight indomethacin (INDO).
  
  
  RESULTS
  Unexpectedly, we found that INDO has a potent direct antiviral activity against the coronaviruses SARS-CoV and CCoV. INDO does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses. This effect is independent of cyclooxygenase inhibition. INDO's potent antiviral activity (>1,000-fold reduction in virus yield) was confirmed in vivo in CCoV-infected dogs.
  
  
  CONCLUSIONS
  The results identify INDO as a potent inhibitor of coronavirus replication and suggest that, having both anti-inflammatory and antiviral activity, INDO could be beneficial in SARS therapy.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Amici
authors.forename: Antonino
authors.initials: A
authors.lastname: Di Caro
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ciucci
authors.forename: Lucia
authors.initials: L
authors.lastname: Chiappa
authors.forename: Concetta
authors.initials: C
authors.lastname: Castilletti
authors.forename: Vito
authors.initials: V
authors.lastname: Martella
authors.forename: Nicola
authors.initials: N
authors.lastname: Decaro
authors.forename: Canio
authors.initials: C
authors.lastname: Buonavoglia
authors.forename: Maria R
authors.initials: MR
authors.lastname: Capobianchi
authors.forename: M Gabriella
authors.initials: MG
authors.lastname: Santoro
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D018352:Coronavirus Infections / Q000188:drug therapy / Q000662:veterinary; D017939:Coronavirus, Canine / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000821:virology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use; D016898:Interferon-alpha / Q000494:pharmacology; D012367:RNA, Viral / Q000302:isolation & purification; D012254:Ribavirin / Q000494:pharmacology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin; D001241:Aspirin; D007213:Indomethacin