title: Inhibitory effect of doxycycline against dengue virus replication in vitro.
abstract: Doxycycline is an antibiotic derived from tetracycline that possesses antimicrobial and anti-inflammatory activities. Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to determine the potential activity of doxycycline against dengue virus replication in vitro. Doxycycline inhibited the dengue virus serine protease (DENV2 NS2B-NS3pro) with an IC50 value of 52.3 ± 6.2 μM at 37 °C (normal human temperature) and 26.7 ± 5.3 μM at 40 °C (high fever temperature). The antiviral activity of doxycycline was first tested at different concentrations against DENV2 using a plaque-formation assay. The virus titter decreased significantly after applying doxycycline at levels lower than its 50 % cytotoxic concentration (CC50, 100 μM), showing concentration-dependent inhibition with a 50 % effective concentration (EC50) of approximately 50 μM. Doxycycline significantly inhibited viral entry and post-infection replication of the four dengue serotypes, with serotype-specific inhibition (high activity against DENV2 and DENV4 compared to DENV1 and DENV3). Collectively, these findings underline the need for further experimental and clinical studies on doxycycline, utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue virus infection.
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia, rothan@um.edu.my.
authors.forename: Hussin A
authors.initials: HA
authors.lastname: Rothan
authors.forename: Zulqarnain
authors.initials: Z
authors.lastname: Mohamed
authors.forename: Mohammadjavad
authors.initials: M
authors.lastname: Paydar
authors.forename: Noorsaadah Abd
authors.initials: NA
authors.lastname: Rahman
authors.forename: Rohana
authors.initials: R
authors.lastname: Yusof
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology*; D004318:Doxycycline / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D010948:Viral Plaque Assay; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C080102:NS2B protein, flavivirus; D017361:Viral Nonstructural Proteins; D004318:Doxycycline