5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus
Orthohantaviruses, previously known as hantaviruses (family Hantaviridae, order Bunyavirales), are emerging zoonoses hosted by different rodent and insectivore species. Orthohantaviruses are transmitted by aerosolized excreta (urine, saliva and feces) of their reservoir hosts. When transmitted to hu...
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doaj-634d3130b1a24b32ab38f405e71dffc92020-11-25T02:05:53ZengMDPI AGViruses1999-49152020-01-0112112210.3390/v12010122v120101225,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of OrthohantavirusGiuseppina Sanna0Sandra Piras1Silvia Madeddu2Bernardetta Busonera3Boris Klempa4Paola Corona5Roberta Ibba6Gabriele Murineddu7Antonio Carta8Roberta Loddo9Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, ItalyDepartment of Chemistry and Pharmacy, University of Sassari, Via Muroni 23/A, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, ItalyInstitute of Virology, Biomedical Research Center Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDepartment of Chemistry and Pharmacy, University of Sassari, Via Muroni 23/A, 07100 Sassari, ItalyDepartment of Chemistry and Pharmacy, University of Sassari, Via Muroni 23/A, 07100 Sassari, ItalyDepartment of Chemistry and Pharmacy, University of Sassari, Via Muroni 23/A, 07100 Sassari, ItalyDepartment of Chemistry and Pharmacy, University of Sassari, Via Muroni 23/A, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, ItalyOrthohantaviruses, previously known as hantaviruses (family Hantaviridae, order Bunyavirales), are emerging zoonoses hosted by different rodent and insectivore species. Orthohantaviruses are transmitted by aerosolized excreta (urine, saliva and feces) of their reservoir hosts. When transmitted to humans, they cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus (cardio) pulmonary syndrome (HPS) in the Americas. Clinical studies have shown that early treatments of HFRS patients with ribavirin (RBV) improve prognosis. Nevertheless, there is the need for urgent development of specific antiviral drugs. In the search for new RNA virus inhibitors, we recently identified a series of variously substituted 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives active against the human respiratory syncytial virus (HRSV). Interestingly, several 2-phenyl-benzotriazoles resulted in fairly potent inhibitors of the Hantaan virus in a chemiluminescence focus reduction assay (C-FRA) showing an EC<sub>50</sub> = 4−5 µM, ten-fold more active than ribavirin. Currently, there are no FDA approved drugs for the treatment of orthohantavirus infections. Antiviral activities and cytotoxicity profiles suggest that 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazoles could be promising candidates for further investigation as a potential treatment of hantaviral diseases.https://www.mdpi.com/1999-4915/12/1/122orthohantavirusphenyl-benzotriazolesantiviral activityc-fra |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giuseppina Sanna Sandra Piras Silvia Madeddu Bernardetta Busonera Boris Klempa Paola Corona Roberta Ibba Gabriele Murineddu Antonio Carta Roberta Loddo |
spellingShingle |
Giuseppina Sanna Sandra Piras Silvia Madeddu Bernardetta Busonera Boris Klempa Paola Corona Roberta Ibba Gabriele Murineddu Antonio Carta Roberta Loddo 5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus Viruses orthohantavirus phenyl-benzotriazoles antiviral activity c-fra |
author_facet |
Giuseppina Sanna Sandra Piras Silvia Madeddu Bernardetta Busonera Boris Klempa Paola Corona Roberta Ibba Gabriele Murineddu Antonio Carta Roberta Loddo |
author_sort |
Giuseppina Sanna |
title |
5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus |
title_short |
5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus |
title_full |
5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus |
title_fullStr |
5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus |
title_full_unstemmed |
5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus |
title_sort |
5,6-dichloro-2-phenyl-benzotriazoles: new potent inhibitors of orthohantavirus |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2020-01-01 |
description |
Orthohantaviruses, previously known as hantaviruses (family Hantaviridae, order Bunyavirales), are emerging zoonoses hosted by different rodent and insectivore species. Orthohantaviruses are transmitted by aerosolized excreta (urine, saliva and feces) of their reservoir hosts. When transmitted to humans, they cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus (cardio) pulmonary syndrome (HPS) in the Americas. Clinical studies have shown that early treatments of HFRS patients with ribavirin (RBV) improve prognosis. Nevertheless, there is the need for urgent development of specific antiviral drugs. In the search for new RNA virus inhibitors, we recently identified a series of variously substituted 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives active against the human respiratory syncytial virus (HRSV). Interestingly, several 2-phenyl-benzotriazoles resulted in fairly potent inhibitors of the Hantaan virus in a chemiluminescence focus reduction assay (C-FRA) showing an EC<sub>50</sub> = 4−5 µM, ten-fold more active than ribavirin. Currently, there are no FDA approved drugs for the treatment of orthohantavirus infections. Antiviral activities and cytotoxicity profiles suggest that 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazoles could be promising candidates for further investigation as a potential treatment of hantaviral diseases. |
topic |
orthohantavirus phenyl-benzotriazoles antiviral activity c-fra |
url |
https://www.mdpi.com/1999-4915/12/1/122 |
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