title: Study the antiviral activity of some derivatives of tetracycline and non-steroid anti inflammatory drugs towards dengue virus.
abstract: Various clinical symptoms are caused by dengue virus ranging from mild fever to severe hemorrhagic fever while there is no successful anti-dengue therapeutics available. Among different strategies towards identifying and developing anti-dengue therapeutics, testing anti-dengue properties of known drugs could represent an efficient strategy for which information of its medical approval, toxicity and side effects is readily available. In this study, we evaluated the antiviral activity of some medical compounds towards dengue NS2B-NS3 protease (DENV2 NS2B-NS3pro) as a target to inhibit dengue virus replication. Mefenamic acid, a non-steroid anti inflammatory drug and doxycycline, a derivative antibiotic of tetracycline both showed significant inhibition potential against DENV2 NS2B-NS3pro Ki values 32 ± 2 μM and 55 ± 5 μM respectively. The effective cytotoxic concentrations of 50% (CC50) against Vero cells were evaluated for mefenamic acid (150 ± 5 μM) and doxycycline (125 ± 4 μM). Concentrations lower than CC50 were used to test the inhibition potential of these compounds against DENV2 replication in Vero cells. The results showed significant reduction in viral load after applying mefenamic acid and doxycyline in concentration dependent manner. Mefenamic acid reduced viral RNA at EC50 of 32 ± 4 μM whilst doxycycline EC50 was 40 ± 3 μM. Mefenamic acid showed higher selectivity against dengue virus replication in vitro compared to doxycycline. These findings underline the need for further experimental and clinical studies on these drugs utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue infection.
authors: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: H A
authors: HA
authors: Rothan
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: M J
authors: MJ
authors: Buckle
authors: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Y A
authors: YA
authors: Ammar
authors: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: P
authors: P
authors: Mohammadjavad
authors: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: O
authors: O
authors: Shatrah
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: A R
authors: AR
authors: Noorsaadah
authors: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Y
authors: Y
authors: Rohana
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D003716:Dengue Virus / Q000187:drug effects* / Q000201:enzymology; D004318:Doxycycline / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D008528:Mefenamic Acid / Q000494:pharmacology / Q000633:toxicity; D020365:RNA Helicases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D014709:Vero Cells; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000998:Antiviral Agents; D004318:Doxycycline; D008528:Mefenamic Acid; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C080102:NS2B protein, flavivirus; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases