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.
The design of a series of styrene and spiroisatin hybrids was based on the structure of combretastatin A-4 1. This library of 20 compounds were synthesized with the pharmacophoric units: 3,4,5-trimethoxy or/and 4-hydroxy-3-methoxy phenyl moities in their structure. Thereby, the libraries of β-nitrostyrenes 10a-10c, spiroisatin-dihydroquinolines 14a-14c, spiroisatinthiazolidinones 17a-17c and spiroisatin-nitropyrrolizidines 20a-20k were evaluated for their in vitro cytotoxic, anti-proliferative, antifungal and antiviral activities. Biological results revealed that among these compounds, β-nitrostyrenes 10a-10c exhibited significant cytotoxicity (HeLa and Jurkat tumor cells) and antifungal (T. mentagrophytes) activities. Moreover, the spiroisatindihydroquinoline 14a and 14c showed promising cytotoxicity (U937 cells). 14a-14c molecules were active against human herpesviruses serotypes 1 and 2 (HHV-1 and HHV-2), but only 14a and 14b were effective against dengue virus serotype 2 (DENV-2). The spiroisatin-nitropyrrolizidine 20c exhibited moderate anti-herpetic activity, while 17c spiroisatin-thiazolidinone derivative also reduced the infection of HHV-1 and DENV-2. Finally, the molecular docking showed that these kind of molecules interact with the subunit α/β-tubulin.
Zika virus (ZIKV), a flavivirus that is mainly transmitted by A. aegypti and A. albopictus and sexual transmission, has been documented and described. The ZIKV RNA detection in the semen of vasectomized men indicates that accessory glands such as the prostate could be a site of virus replication. In this study, we characterized the ZIKV infection, evaluated the antiviral profile, and demonstrated the AXL and TIM-1 expression on the PC3 prostate cell line. It was also determined that PC3 cells are susceptible and permissive to ZIKV infection without altering the cell viability or causing a cytopathic effect. The antiviral profile suggests that the PC3 cells modulate the antiviral response through the suppressor molecule expression, SOCS-1, during a ZIKV infection.
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