Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy

Tan, Li Yin; Komarasamy, Thamil Vaani; James, William; Balasubramaniam, Vinod

doi:10.3389/fmicb.2022.743147

Cited by 13 publications

(13 citation statements)

References 114 publications

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“…The search for drugs suitable for repositioning has helped pregnant women and newborns to withstand the outbreaks of ZIKV (48, 49). Of the repositioning drugs listed in Table 2, only temoporfin can be given to pregnant women (49). The anti-ZIKV medications sofosbuvir, chloroquine, and suramin produced better outcomes because more experimental data were available for evaluation (48).…”

Section: Antiviral Drugsmentioning

confidence: 99%

ZIKV: Epidemiology, infection mechanism and current therapeutics

et al. 2023

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The Zika virus (ZIKV) is a vector-borne flavivirus that has been detected in 87 countries worldwide. Outbreaks of ZIKV infection have been reported from various places around the world and the disease has been declared a public health emergency of international concern. ZIKV has two modes of transmission: vector and non-vector. The ability of ZIKV to vertically transmit in its competent vectors, such as Aedes aegypti and Aedes albopictus, helps it to cope with adverse conditions, and this could be the reason for the major outbreaks that occur from time to time. ZIKV outbreaks are a global threat and, therefore, there is a need for safe and effective drugs and vaccines to fight the virus. In more than 80% of cases, ZIKV infection is asymptomatic and leads to complications, such as microcephaly in newborns and Guillain–Barré syndrome (GBS) in adults. Drugs such as sofosbuvir, chloroquine, and suramin have been found to be effective against ZIKV infections, but further evaluation of their safety in pregnant women is needed. Although temoporfin can be given to pregnant women, it needs to be tested further for side effects. Many vaccine types based on protein, vector, DNA, and mRNA have been formulated. Some vaccines, such as mRNA-1325 and VRC-ZKADNA090-00-VP, have reached Phase II clinical trials. Some new techniques should be used for formulating and testing the efficacy of vaccines. Although there have been no recent outbreaks of ZIKV infection, several studies have shown continuous circulation of ZIKV in mosquito vectors, and there is a risk of re-emergence of ZIKV in the near future. Therefore, vaccines and drugs for ZIKV should be tested further, and safe and effective therapeutic techniques should be licensed for use during outbreaks.

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Section: Antiviral Drugsmentioning

confidence: 99%

ZIKV: Epidemiology, infection mechanism and current therapeutics

et al. 2023

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“…Before ZIKV can invade the brain of the infected mother and infect the fetus, it must overcome two obstacles, namely the placental barrier (BPB) [ 18 ] and the BBB [ 19 ]. However, the mechanism underlying this infiltration is not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

“…The placenta acts as the first barrier for the fetus, protecting it from pathogens and promoting its growth and development. The BBB acts as the fetus’ second barrier, protecting the fetal brain and ensuring healthy brain development [ 19 ]. It is an intricate structure composed of tightly connected brain microvascular endothelial cells (BMECs) associated with pericytes, astrocytes, and microglia.…”

Section: Introductionmentioning

confidence: 99%

Exploring Zika Virus Impact on Endothelial Permeability: Insights into Transcytosis Mechanisms and Vascular Leakage

Henrio Marcellin,

Huang

2024

Viruses

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Treating brain disease is challenging, and the Zika virus (ZIKV) presents a unique obstacle due to its neuroinvasive nature. In this review, we discuss the immunopathogenesis of ZIKV and explore how the virus interacts with the body’s immune responses and the role of the protein Mfsd2a in maintaining the integrity of the blood–brain barrier (BBB) during ZIKV neuroinvasion. ZIKV has emerged as a significant public health concern due to its association with severe neurological problems, including microcephaly and Gillain–Barré Syndrome (GBS). Understanding its journey through the brain—particularly its interaction with the placenta and BBB—is crucial. The placenta, which is designed to protect the fetus, becomes a pathway for ZIKV when infected. The BBB is composed of brain endothelial cells, acts as a second barrier, and protects the fetal brain. However, ZIKV finds ways to disrupt these barriers, leading to potential damage. This study explores the mechanisms by which ZIKV enters the CNS and highlights the role of transcytosis, which allows the virus to move through the cells without significantly disrupting the BBB. Although the exact mechanisms of transcytosis are unclear, research suggests that ZIKV may utilize this pathway.

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“…Targeting host factors rather than viral enzymes has emerged as a viable therapeutic approach to suppress viral replication [ 2 ]. Understanding the dynamic response of host molecules during viral infection is necessary for the development of better therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles

Zhang

Tan

Wei

et al. 2023

Emerging Microbes & Infections

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Zika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future.

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Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy

Cited by 13 publications

References 114 publications

ZIKV: Epidemiology, infection mechanism and current therapeutics

ZIKV: Epidemiology, infection mechanism and current therapeutics

Exploring Zika Virus Impact on Endothelial Permeability: Insights into Transcytosis Mechanisms and Vascular Leakage

Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles

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