title: Fighting arboviral diseases: low toxicity on mammalian cells,  dengue growth inhibition (in vitro), and mosquitocidal activity  of Centroceras clavulatum-synthesized silver nanoparticles.
abstract: Dengue is a mosquito-borne viral disease that has rapidly spread in all regions of the world in recent years. Female mosquitoes, mainly Aedes aegypti, transmit dengue. Approximately 3,900 million people, in 128 countries, are at risk of dengue infection. Recently, a focus has been provided on the potential of green-synthesized nanoparticles as inhibitors of the production of dengue viral envelope (E) protein in Vero cells and downregulators of the expression of dengue viral E gene. Algae are an outstanding reservoir of novel compounds, which may help in the fight against mosquito-borne diseases. In this research, silver nanoparticles (AgNP) were rapidly synthesized using a cheap extract of the alga Centroceras clavulatum. AgNP were characterized by UV–vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). In mosquitocidal assays, LC50 values of C. clavulatum extract against A. aegypti larvae and pupae were 269.361 ppm (larva I), 309.698 ppm (larva II), 348.325 ppm (larva III), 387.637 ppm (larva IV), and 446.262 ppm (pupa). C. clavulatum extract also exhibited moderate antioxidant activity, both in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging assays. LC50 values of C. clavulatum-synthesized AgNP were 21.460 ppm (larva I), 23.579 ppm (larva II), 25.912 ppm (larva III), 29.155 ppm (larva IV), and 33.877 ppm (pupa). Furthermore, C. clavulatum-synthesized AgNP inhibited dengue (serotype dengue virus type-2 (DEN-2)) viral replication in Vero cells. Notably, 50 μg/ml of green-synthesized AgNP showed no cytotoxicity on Vero cells while reduced DEN-2 viral growth of more than 80%; 12.5 μg/ml inhibited viral growth of more than 50%. Cellular internalization assays highlighted that untreated infected cells showed high intensity of fluorescence emission, which denotes high level of viral internalization. Conversely, AgNP-treated infected cells showed reduced levels of fluorescence, failing to show significant viral load. Overall, our study showed that alga-mediated synthesis of metal nanoparticles may be considered to develop newer, safer, and cheap tools in the fight against the dengue virus, serotype DEN-2, and its vector A. aegypti, with little cytotoxicity on mammalian cells.
authors.forename: Kadarkarai
authors.initials: K
authors.lastname: Murugan
authors.forename: Palanimuthu
authors.initials: P
authors.lastname: Aruna
authors.forename: Chellasamy
authors.initials: C
authors.lastname: Panneerselvam
authors.forename: Pari
authors.initials: P
authors.lastname: Madhiyazhagan
authors.forename: Manickam
authors.initials: M
authors.lastname: Paulpandi
authors.forename: Jayapal
authors.initials: J
authors.lastname: Subramaniam
authors.forename: Rajapandian
authors.initials: R
authors.lastname: Rajaganesh
authors.forename: Hui
authors.initials: H
authors.lastname: Wei
authors.forename: Mohamad Saleh
authors.initials: MS
authors.lastname: Alsalhi
authors.forename: Sandhanasamy
authors.initials: S
authors.lastname: Devanesan
authors.forename: Marcello
authors.initials: M
authors.lastname: Nicoletti
authors.forename: Ban
authors.initials: B
authors.lastname: Syuhei
authors.forename: Angelo
authors.initials: A
authors.lastname: Canale
authors.forename: Giovanni
authors.initials: G
authors.lastname: Benelli
mesh_terms: D000330:Aedes; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003715:Dengue / Q000517:prevention & control / Q000635:transmission; D003716:Dengue Virus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D005260:Female; D007303:Insect Vectors; D007306:Insecticides; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D007928:Lethal Dose 50; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D010851:Picrates / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry; D011679:Pupa / Q000187:drug effects / Q000254:growth & development; D000461:Rhodophyta / Q000378:metabolism*; D012834:Silver; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D014961:X-Ray Diffraction
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D007306:Insecticides; D010851:Picrates; D009569:Nitric Oxide; D012834:Silver; C004931:1,1-diphenyl-2-picrylhydrazyl