Zika Virus: Origins, Pathological Action, and Treatment Strategies

Abstract

The Zika virus (ZIKV) global epidemic prompted the World Health Organization to declare it a 2016 Public Health Emergency of International Concern. The overwhelming experience over the past several years teaches us that ZIKV and the associated neurological complications represent a long-term world-wide challenge to public health. Although the number of ZIKV cases in the Western Hemisphere has dropped since 2016, the need for basic research and anti-ZIKV drug development remains strong. Re-emerging viruses like ZIKV are an ever-present threat in the 21st century where fast transcontinental travel lends itself to viral epidemics. Here, we first present the origin story for ZIKV and review the rapid progress researchers have made toward understanding of the ZIKV pathology and in the design, re-purposing, and testing–particularly in vivo–drug candidates for ZIKV prophylaxis and therapy ZIKV. Quite remarkably, a short, but intensive, drug-repurposing effort has already resulted in several readily available FDA-approved drugs that are capable of effectively combating the virus in infected adult mouse models and, most importantly, in both preventing maternal-fetal transmission and severe microcephaly in newborns in pregnant mouse models.

Congenital Zika Virus Infection: a Review with Emphasis on the Spectrum of Brain Abnormalities

“…The antimalarial drug chloroquine inhibits ZIKV infection limiting vertical transmission of ZIKV infection and fetal growth defects when used in pregnant mice [92]. Several candidate ZIKV vaccines are currently under development, being already on phase 1 clinical trials [93]. Surgical interventions, such as ventriculoperitoneal shunt procedure, are indicated for children with progressive ventricular enlargement due to hydrocephalus [59,60].…”

Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier

“…For example, WNV, Japanese encephalitis virus (JEV), Usutu virus, and chikungunya virus are well described as determinants of neurological impairments in some patients, which can be in some cases fatal for the host ( 9 ). Recently, Zika virus (ZIKV) reemerged in the Pacific Islands and in South America, causing a major epidemic ( 10 ). ZIKV belongs to the Flaviviridae family and is a small single-stranded RNA enveloped virus isolated in 1947 in the Zika forest in Uganda ( 11 ).…”

“…ZIKV is transmitted mainly by the mosquito Aedes aegypti , but other less classical modes for an arbovirus have been described, including blood transfusion, sexual, and mother-to-child transmissions ( 13 ). Because of the extent of the American epidemic (more than one million patients were affected), severe forms of the disease were reported, including serious neurological complications such as Guillain-Barré syndrome (GBS) and congenital Zika syndrome (CZS) consisting of microcephaly and other neurodevelopmental defects ( 10 , 13 , 14 ). Regarding CZS, studies demonstrated that ZIKV can cross the blood-placental barrier and replicate in the placenta and in the developing embryo, including the brain, resulting in severe malformations at birth ( 15 ).…”

“…Several studies are starting to describe the ZIKV neurovirulence molecular and cellular mechanisms ( 10 ). One of the key issues remaining, however, is the characterization of the mechanisms governing ZIKV CNS access.…”

Evidence, rationality, and ignorance: Agnotological issues in COVID-19 science

“…Microorganisms and diseases are traditionally named after the place in which they are first reported. Examples include Zika 24 , Ebola 25 , and Rocky Mountain Spotted Fever 26 . The issue of stigma against local residents was raised when a novel hantavirus was named Muerto Canyon after it was discovered in a Navajo Reservation with the same name.…”