Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism

Potential Therapeutics: Toe Hold in the Fight against Zika Virus

“…Reports have demonstrated that various anti-influenza compounds show some degree of anti-Zika activity [64]. We speculate that combinational treatments with monoclonal neutralizing antibody like ZIKV-117, Z23 or Z3L1 and an antiviral drug, such as an antiinfluenza drug, may result in better treatment outcomes in Zika infection.…”

“…Researchers from the University of Helsinki have recently shown that three drugs, called obatoclax, saliphenylhalamide, and gemcitabine prevented synthesis of viral building blocks and production of new viruses at concentrations that were not toxic to cells [64]. In this study, human retinal pigment epithelial cells were infected with a Zika virus strain isolated from fetal brains.…”

The Race To Find Antivirals for Zika Virus

“…Regarding NITD008, this compound also exhibited antiviral activity in A129 mice deficient in type I interferon receptor treated with 50 mg/kg/day of the drug, as all vehicle-treated mice died within 12 days after ZIKV infection, whereas 50% of the NITD008-treated animals survived without developing any neurological signs (25). In this line, it has also been reported that gemcitabine, a nucleoside that interferes with de novo pyrimidine biosynthesis, inhibited ZIKV multiplication (EC 50 , 1 M; SI, Ͼ1,000) by interfering with the transcription of viral RNA (26). Similarly, another screening also identified the thymidylate synthetase inhibitor 5-fluorouracil, an anticancer drug, as a potent inhibitor of ZIKV multiplication (EC 50 , 14.3 M; SI, Ͼ2.5)(24), further supporting pyrimidine synthesis inhibitors as potential antiviral candidates against ZIKV.…”

“…By using human osteosarcoma cells (U2OS), it was shown that up to 38 molecules blocked flavivirus infection, including nanchangmycin (IC 50 , 0.1 M), a natural product of Streptomyces nanchangensis that was shown to have insecticidal activity against silkworms and anti-bacterial activity in vitro, tenovin-1 (IC 50 , 0.7 M), which protects against MDM2-mediated p53 degradation, MPA (IC 50 , 0.4 M), and gemcitabine (IC 50 , 0.3 M). MPA and gemcitabine have also been reported to be ZIKV inhibitors by others (26,43). A less potent effect was also observed in human brain microvascular endothelial cells (hBMECs), an immortalized model of the human blood-brain barrier micro vasculature that may be involved in ZIKV access to fetal brain.…”

Current Advances in Zika Virus Transmission: Urgency for Effective Therapeutics and Prevention

“…Gemcitabine ( C 9 H 11 F 2 N 3 O 4 ), Obatoclax (C 21 H 23 N 3 O 4 S) and Saliphenylhalamide (C 28 H 29 NO 5 ) interferes with de novo pyrimidine biosynthesis which inhibits ZIKV replication by interfering with the transcription, translation and post translation modifications of viral RNA (Kuivanen et al, 2017).…”