Anti-Zika virus activity of several abietane-type ferruginol analogues

Sousa, Francielle Tramontini Gomes de; Bormio-Nunes, Cristina; Romano, Camila Malta; Sabino, Éster Cerdeira; González-Cardenete, Miguel A.

doi:10.1590/s1678-9946202062097

Cited by 13 publications

(16 citation statements)

References 13 publications

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“…In previous results published by our group, the anti-herpetic and anti-DENV activities have been evaluated for compound 6 . This molecule has its antiviral effect mainly in postinfection stages: in DENV-2 with 50% effective antiviral concentration (EC 50 ) of 1.4 μM and for herpes virus type 2 (HHV-2) of 19.2 μM, as well as for a Brazilian Zika (clinical isolate, IMT17) virus strain of 7.7 μM . Therefore, since the compounds ferruginol ( 5 ), ferruginol analogue 6 , 14 , 18b , and 24 presented better results in the preliminary screening, the broad-spectrum antiviral activity was evaluated in postinfection stages.…”

Section: Resultsmentioning

confidence: 99%

Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids

et al. 2022

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Viral infections affect several million patients annually. Although hundreds of viruses are known to be pathogenic, only a few can be treated in the clinic with available antiviral drugs. Naturally based pharmacotherapy may be a proper alternative for treating viral diseases. Several natural and semisynthetic abietane-type diterpenoids have shown important antiviral activities. In this study, a biological evaluation of a number of either C-18- or C-19-functionalized known semisynthetic abietanes against Zika virus , Dengue virus , Herpes virus simplex type 1, and Chikungunya virus are reported. Semisynthetic abietane ferruginol and its analogue 18-(phthalimid-2-yl)ferruginol displayed broad-spectrum antiviral properties. The scale-up synthesis of this analogue has been optimized for further studies and development. This molecule displayed an EC 50 between 5.0 and 10.0 μM against Colombian Zika virus strains and EC 50 = 9.8 μM against Chikungunya virus. Knowing that this ferruginol analogue is also active against Dengue virus type 2 (EC 50 = 1.4 μM, DENV-2), we can conclude that this compound is a promising broad-spectrum antiviral agent paving the way for the development of novel antivirals.

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Section: Resultsmentioning

confidence: 99%

Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids

et al. 2022

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“…Their preferred natural cleavage site is at the C-terminal side of a multibasic amino acid sequence containing predominantly arginine and sometimes lysine in the P1-position, and at least one additional or even two more basic residues in P2- and P3-positions. With a few exceptions, the P1′-position is limited to small residues, such as glycine, alanine, and serine. − As a consequence, di- or tribasic P3-P1 segments are a common motif in the majority of substrate analogue flavivirin inhibitors with high affinity. − Besides linear peptide derivatives, further active-site-directed inhibitors such as cyclic peptides, − small molecules, − and natural products − have been described for the ZIKV protease. Furthermore, several attempts of addressing allosteric binding sites have been reported. ,,− …”

Section: Introductionmentioning

confidence: 99%

Structure-Based Optimization and Characterization of Macrocyclic Zika Virus NS2B-NS3 Protease Inhibitors

et al. 2022

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Zika virus (ZIKV) is a human pathogenic arbovirus. So far, neither a specific treatment nor a vaccination against ZIKV infections has been approved. Starting from our previously described lead structure, a series of 29 new macrocyclic inhibitors of the Zika virus protease containing different linker motifs have been synthesized. By selecting hydrophobic d-amino acids as part of the linker, numerous inhibitors with K i values < 5 nM were obtained. For 12 inhibitors, crystal structures in complex with the ZIKV protease up to 1.30 Å resolution were determined, which contribute to the understanding of the observed structure–activity relationship (SAR). In immunofluorescence assays, an antiviral effect was observed for compound 26 containing a d-homocyclohexylalanine residue in its linker segment. Due to its excellent selectivity profile and low cytotoxicity, this inhibitor scaffold could be a suitable starting point for the development of peptidic drugs against the Zika virus and related flaviviruses.

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“…18‐oxoferruginol is an abietane diterpenoid whose anti‐ZIKV activity was evaluated in vitro 89 . Among the abietane analogues tested, 18‐oxoferruginol presented the best selectivity index of 13.51 with a CC 50 value of 35.09 ± 5.20 µM and an EC 50 value of 2.60 ± 0.07 µM.…”

Section: Inhibitors With Unknown Targetsmentioning

confidence: 99%

Natural products as Zika antivirals

Fong

Chu

2022

Medicinal Research Reviews

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Zika virus (ZIKV) is an arbovirus belonging to the flavivirus genus and is transmitted in Aedes mosquito vectors. Since its discovery in humans in 1952 in Uganda, ZIKV has been responsible for many outbreaks in South America, Africa, and Asia. Patients infected with ZIKV are usually asymptomatic; mild symptoms include fever, joint and muscle pain, and fatigue. However, severe infections may have neurological implications, such as Guillain-Barré syndrome and fetal microcephaly. To date, there are no existing approved therapeutic drugs or vaccines against ZIKV infections; treatments mainly target the symptoms of infection.Preventive measures against mosquito breeding are the main strategy for limiting the spread of the virus. Antiviral drug research for the treatment of ZIKV infection has been rapidly developing, with many drug candidates emerging from drug repurposing studies, and compound screening. In particular, several studies have demonstrated the potential of natural products as antivirals for ZIKV infection. Hence, this paper will review recent advances in natural products in ZIKV antiviral drug discovery.

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Anti-Zika virus activity of several abietane-type ferruginol analogues

Cited by 13 publications

References 13 publications

Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids

Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids

Structure-Based Optimization and Characterization of Macrocyclic Zika Virus NS2B-NS3 Protease Inhibitors

Natural products as Zika antivirals

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