Repurposing drugs for use against Zika virus infection

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus for which there are no vaccines or specific therapeutics. To find drugs active on the virus is a complex, expensive and time-consuming process. The prospect of drug repurposing, which consists of finding new indications for existing drugs, is an interesting alternative to expedite drug development for specific diseases. In theory, drug repurposing is also able to respond much more rapidly to a crisis than a classical drug discovery process. Consequently, the methodology is attractive for vector-borne diseases that can emerge or re-emerge worldwide with the risk to become pandemic quickly. Different drugs, showing various structures, have been repurposed to be used against ZIKV infection. They are reviewed in this study and the conditions for their potential use in practice are discussed.

Azithromycin Inhibits the Replication of Zika Virus

“…A first strategy consists in drug repurposing by screening large libraries of compounds, including approved compounds [6][7][8][9]30]. This strategy detected active drugs on ZIKV but most of them cannot be used in pregnant women.…”

Computer-Assisted and Data Driven Approaches for Surveillance, Drug Discovery, and Vaccine Design for the Zika Virus

“…Chloroquine Derivatives particularly at the C-4 position of N-(2-arylmethylimino)ethyl-7-chloroquinolin-4-amine derivatives [98] Quinacrine (QC), Mefloquine (MQ), and GSK369796 Antimalarial aminoquinoline derivatives [41,87] PHA-690509 Cyclin dependent kinase (CDK) inhibitor [99] Lapachol, HMC-HO1α and Ivermectin…”

“…Another RdRp inhibitor, NITD008, an adenosine nucleoside analog, has also exhibited antiviral activity against ZIKV in vitro with EC50 at the sub-micro molar range (0.28-0.95 µM). Although when NITD008 was treated with 50 mg/kg in the A129 mouse model, it protected 50% of the infected mice from death without symptoms of neurological disorder [129], the compound was discarded to other undesirable toxic effects in clinical testing [99].…”

“…Although no drug has yet been approved by FDA for the treatment of ZIKV infection, numerous small molecules have been identified that have shown anti-ZIKV activity [99,112,142]. However, most of these anti-ZIKV small molecules are shown to be only active in in vitro cell assays.…”

Repurposing approved drugs on the pathway to novel therapies

“…In light of the problems with bringing a new drug to market, many researchers consider screening Food and Drug Administration (FDA)‐approved drugs for repurposing a lower risk than de novo drug design . Searching for specific molecules for a novel drug target may be perceived as unrealistically slow, especially during emerging disease outbreaks . Thus, the approximately 4000 compounds used in the clinic are now being reinvestigated, to see what other treatments they could provide for difficult to treat conditions.…”