A Review on the Current Knowledge on ZIKV Infection and the Interest of Organoids and Nanotechnology on Development of Effective Therapies against Zika Infection

Abstract

Zika virus (ZIKV) acquired a special relevance due to the pandemic that occurred in the Americas in 2015, when an important number of fetal microcephaly cases occurred. Since then, numerous studies have tried to elucidate the pathogenic mechanisms and the potential therapeutic approaches to combat the virus. Cellular and animal models have proved to be a basic resource for this research, with the more recent addition of organoids as a more realistic and physiological 3D culture for the study of ZIKV. Nanotechnology can also offer a promising therapeutic tool, as the nanoparticles developed by this field can penetrate cells and deliver a wide array of drugs in a very specific and controlled way inside the cells. These two state-of-the-art scientific tools clearly provide a very relevant resource for the study of ZIKV, and will help researchers find an effective treatment or vaccine against the virus.

Pregnancy and pandemics: Interaction of viral surface proteins and placenta cells

“…The ZIKA virus (ZIKV) belongs to the family of Flaviviridae and was first isolated from a rhesus monkey in 1947 [ 96 ]. ZIKV is a single-stranded RNA virus that possesses a genome of around 11 kb, which is translated into a big polyprotein encoding 10 viral proteins, including the 3 structural proteins: capsid protein (C), precursor protein (prM) and envelope protein (E); and 7 non-structural proteins (NS) used by the virus to orchestrate viral replication or to avoid host defenses [ 97 ]. Other known members of Flaviviridae are Dengue Virus, West Nile Virus and Yellow Fever virus [ 98 ] and much of current research on ZIKV is based on knowledge from their previous studies.…”

“…Due to its thermostability, ZIKV is detectable in diverse human body fluids like semen, saliva, breast milk or urine, even days or weeks after the disappearance of the clinical symptoms [ 99 ]. Hence, some cases of ZIKV infection have occurred by sexual contact, blood or platelet transfusion, mother-to child transmission during pregnancy and, very rarely, upon close contact in a single reported case [ 97 ]. Other factors such as virus strain [ 105 ], targeted cell type [ 106 ], pregnancy stage [ 107 ] and previous infection with Dengue Virus [ 108 , 109 ] influence ZIKV infection both in vitro and in vivo.…”

“…Viral protein E is the most abundant in the ZIKV surface and mediates binding to host cell receptors mostly through C-type lectin receptors, followed by entry by endocytosis. Other cellular phosphatidylserine receptors, such as T cell immunoglobulin mucin (TIM) and several tyrosine kinase receptor (TAM) families (TYRO3, AXL and MER) or Glycosaminoglycans have been proposed, but further studies are needed [ 97 , 98 ].…”

Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?

“…Although microcephaly can be analyzed in murine models, the gestational period is too short in comparison to the human one, thus a pre-natal ZIKV infection model is missing. Conversely, pregnant primates transmit the virus [96] and exhibit fetus lesions similarly to those observed in humans with congenital Zika syndrome (CZS) [97].…”

Rational selection of hidden epitopes for a molecularly imprinted electrochemical sensor in the recognition of heat-denatured dengue NS1 protein

“…Yellow fever virus, Japanese encephalitis virus, dengue virus (DENV) and zika virus (ZIKV) are the most frequent human infections caused by these vector-borne diseases. The ZIKV outbreaks of 2013 and 2015, as well as the relation of ZIKV to the increase in fetal and newborn microcephaly cases, reinforced the need for early diagnosis (Gasco and Muñoz-Fernández, 2020). Dengue is a vector-borne disease transmitted to a human host through the bite of an Aedes aegypti or A. albopictus mosquito infected with DENV.…”