Drugs for the Treatment of Zika Virus Infection

Bernatchez, Jean A.; Tran, Lana; Li, Jerry; Luan, Yun; Siqueira-Neto, Jair L.; Li, Rongshi

doi:10.1021/acs.jmedchem.9b00775

Cited by 78 publications

(69 citation statements)

References 148 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several drug candidates have been identified, although only a small number have advanced to clinical trials. Development of therapeutic interventions, either to be given prophylactically during an outbreak or therapeutically after identification of early infection, which could prevent the adverse outcomes associated with prenatal Zika virus infection, continue to be a focus of research (Bernatchez et al, 2020).…”

Section: Prevention Of the Adverse Outcomes Caused By Prenatal Zikamentioning

confidence: 99%

Teratogen update: Zika virus and pregnancy

Rasmussen

Jamieson

2020

Birth Defects Research

View full text Add to dashboard Cite

Zika virus was first identified in Uganda in 1947 but received little attention until 2015 when a large outbreak of Zika virus illness followed by an increased number of babies born with microcephaly occurred in Brazil. Zika virus spread rapidly throughout the Americas, and in 2016 was identified as a cause of microcephaly and other serious birth defects. Since that time, much has been learned about the Zika virus. The virus is primarily spread by the bite of Aedes species mosquitoes; however, other forms of transmission (e.g., sexual and intrauterine) have been recognized. Although postnatal Zika virus infection typically causes mild or no symptoms, effects on infants born to prenatally infected mothers can be severe and include structural birth defects and neurodevelopmental effects. The risk of a structural birth defect among infants born to mothers with confirmed or suspected Zika virus infection during pregnancy has ranged from 5 to 10%. The timing of Zika infection during pregnancy affects risk, with higher risks with the first‐trimester infection. Neurodevelopmental effects are seen even in infants who appear normal in the newborn period. Although cases of Zika virus infection have fallen in the Americas, the Zika virus remains an active threat in some regions of the world. The development of a Zika vaccine will require continued focus and investment. Until a Zika vaccine is available, prevention efforts for pregnant women include avoidance of travel to areas with active Zika transmission, avoidance of mosquito bites for those living in or traveling to areas with Zika transmission, and protection against sexual transmission.

show abstract

Section: Prevention Of the Adverse Outcomes Caused By Prenatal Zikamentioning

confidence: 99%

Teratogen update: Zika virus and pregnancy

Rasmussen

Jamieson

2020

Birth Defects Research

View full text Add to dashboard Cite

show abstract

“…In addition, in vitro experiments demonstrate that trophoblastic cells become progressively more resistant to infection by ZIKV during pregnancy, partly through the secretion of IFNs [26]. In this context, a lot of efforts were raised to provide funds to deeply investigate how to avoid another spread of Zika virus infection, as well as drugs tests and vaccine development based on viral proteins, DNA vaccines, Virus Like Particles (VLP), chimeric viruses, among other strategies [27][28][29][30]. Therefore, there are few studies to investigate the pregnancy immunity and how the immune interface mother-to-child could contribute to infection spread with drastic consequences to fetus [21,[31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Innate Immunity Modulation during Zika Virus Infection on Pregnancy: What We Still Need to Know for Medical Sciences Breakthrough

Azamor¹,

Torrentes-Carvalho²,

Vasconcelos³

et al. 2021

Cell Interaction - Molecular and Immunological Basis for Disease Management

View full text Add to dashboard Cite

Zika virus (ZIKV), an arthropod-borne flavivirus, was classified as reemerging infectious disease and included as neglected tropical disease. During the recent ZIKV outbreak in South America, it has been demonstrated that ZIKV infection during pregnancy is strongly associated with fetal loss, malformations and neurological disorders in newborns. Despite the first line of host immune defense is related to innate immunity activation, the immunological homeostasis is essential for pregnancy success. Although the dynamic changes in maternal-fetal immunity is not completely understood and poorly investigated, the knowledge of immune responses during gestation is very important for infectious disease prevention and control, as ZIKV. Here, we put together more and new information about the innate immunity during gestation, highlighting three parts probably involved with clinical outcome and/or not well explored in literature: 1) type III interferon; 2) innate regulatory cells; and 3) cell death pathways modulation. Additionally, we will be focused on discussing how the dynamic responses of innate immune system during pregnancy and its effects in newborns, could be modulated by ZIKV, as well as how efforts on development of new/old drugs and vaccines could be effective for ZIKV prevention and control to provide a successful pregnancy.

show abstract

“…However, its use remains limited to children with confirmed prior infection. In addition, no post-exposure therapeutic options are available for patients infected with these viruses; current treatments only attempt to alleviate the symptoms (Bernatchez et al, 2020;Lim, 2019;Lim et al, 2013). Antiviral strategies often focus on directly targeting viral proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Antiviral strategies often focus on directly targeting viral proteins. While molecules inhibiting for instance the flavivirus RNAdependent RNA polymerase NS5 or the protease NS3 have been identified, the high mutation rate of the virus allows for resistance to be developed quickly (Bernatchez et al, 2020;Carrasco-Hernandez et al, 2017;Garcia et al, 2017). One increasing area of exploration for alternative therapeutic approaches is the targeting of host factors that are critical for virus propagation (Kaufmann et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Dengue and Zika virus infection are impaired by small molecule ER proteostasis regulator 147 in an ATF6-independent manner

Almasy

Davies

Lisy

et al. 2020

Preprint

View full text Add to dashboard Cite

Flaviviruses, including Dengue and Zika, are widespread human pathogens, however, no broadly active therapeutics exist to fight infection. Here, we establish the recently discovered pharmacologic modulator of ER proteostasis 147 as an effective hostcentered antiviral strategy. Compound 147 reduces infection by attenuating viral replication without causing toxicity in host cells. 147 is a preferential activator of the ATF6 pathway of the unfolded protein response, which requires targeting of cysteine residues primarily on protein disulfide isomerases (PDIs). We find that the antiviral activity of 147 is independent of ATF6 induction but does require modification of reactive thiols on protein targets. Targeting PDIs using RNAi and other PDI small molecule inhibitors was unable to recapitulate the antiviral effects, suggesting additional identified protein targets of 147 may mediate the activity. Importantly, 147 can impair infection of multiple strains of Dengue and Zika virus, indicating that it is suitable as a broad-spectrum antiviral agent.

show abstract

Drugs for the Treatment of Zika Virus Infection

Cited by 78 publications

References 148 publications

Teratogen update: Zika virus and pregnancy

Teratogen update: Zika virus and pregnancy

Innate Immunity Modulation during Zika Virus Infection on Pregnancy: What We Still Need to Know for Medical Sciences Breakthrough

Dengue and Zika virus infection are impaired by small molecule ER proteostasis regulator 147 in an ATF6-independent manner

Contact Info

Product

Resources

About