Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

doi:10.1007/s11684-021-0834-9

Front. Med.

2021, Vol. 15

Issue (3) : 404-415 https://doi.org/10.1007/s11684-021-0834-9

REVIEW

Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin(

), Jiandong Jiang(

)

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

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Abstract

Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain–Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.

Keywords Zika virus clinical drugs ZIKV inhibitors antivirals repurposing

Corresponding Author(s): Yuan Lin,Jiandong Jiang

Just Accepted Date: 17 November 2020 Online First Date: 16 December 2020 Issue Date: 18 June 2021

Cite this article:

Weibao Song,Hongjuan Zhang,Yu Zhang, et al. Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection[J]. Front. Med., 2021, 15(3): 404-415.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0834-9
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I3/404

Fig.1 Overview of ZIKV replication in the infected cells and the important drug targets that can be inhibited by anti-ZIKV agents discussed in this review.

Name	Structure	Original use	Anti-ZIKV activity		Mode of action	Drug status	References
Name	Structure	Original use	In vitro EC₅₀	In vivo	Mode of action	Drug status	References
Sofosbuvir		HCV therapy	0.41 µmol/L	Active in C57BL/6J mice	Inhibitor of RdRp	Class B FDA-approved drug	[29,34,42]
Emetine		Intestinal amoebiasis and amoebic liver abscess treatment	52.9 nmol/L	Active in female SJL mice and Ifnar1⁻^/⁻ mice	Inhibitor of RdRp	FDA-approved drug	[47]
Niclosamide		Worm infections treatment	0.42–0.54 µmol/L	−	Inhibitor of NS2/NS3 interaction	Class B FDA-approved drug	[19,30]
Temoporfin		Squamous cell carcinoma of the head and neck treatment	0.02–0.027 µmol/L	Active in Balb/C mice	Inhibitor of NS2/NS3 interaction	FDA-approved drug	[30,57]
Nitazoxanide		Various helminthic and protozoal infections treatment	0.39–1.66 µmol/L	−	Inhibitor of NS2/NS3 interaction	Class B FDA-approved drug	[30,58]
Novobiocin		Antibiotic	26.12–38.14 µg/mL	Active in dexamethasone-immunosuppressed mice	Inhibitor of NS2/NS3 interaction	Class C FDA-approved drug	[61]
Bromocriptine		Galactorrhea and Parkinson’s disease treatment	13 µmol/L	−	Inhibitor of NS2/NS3 interaction	FDA-approved drug	[63]
Chloroquine		Malaria and rheumatoid arthritis treatment	9.82 µmol/L	Active in SJL mice	Disrupting the pH-dependent steps of viral replication	Class C FDA-approved drug	[28,73,74]
Hydroxychloroquine		Antimalarial	−	Active in WT pregnant mice	Alkalizing intracellular acidic organelles; reducing autophagic activity	Class C FDA-approved drug	[84,85]
Mefloquine		Antimalarial	3.6–10 µmol/L	−	−	Class B FDA-approved drug	[18,92]
Amodiaquine		Antimalarial	2.8 µmol/L	SCID-beige mice	Targeting an early step of viral replication	Class C FDA-approved drug	[75,94]
Azithromycin		Antibiotic	2–15 µmol/L	−	−	FDA-approved drug	[98,100]
Daptomycin		Antibiotic	1.0 µmol/L	−	−	Class B FDA-approved drug	[18,102]
Emricasan		Hepatic injury and liver fibrosis treatment	−	−	Inhibiting caspases	Phase II clinical trials	[19]
Suramin		African trypanosomiasis and adult Onchocerca treatment	39.8 µmol/L	−	Affecting virus attaching stage and the release of infectious progeny	Investigational	[111]

Tab.1 Summary of repurposing drugs described in this review

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