Trehalose May Decrease the Transmission of Zika Virus to the Fetus by Activating Degradative Autophagy

Yuan, Shu; Zhang, Zhongwei; Li, Zi-Lin

doi:10.3389/fcimb.2017.00402

Cited by 11 publications

(10 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hydroxychloroquine blocked ZIKV spread in a mouse model [12] and we found it decreased titers in both Vero and C6/36 cells. While trehalose, an autophagy inducer, has been suggested to block ZIKV transmission [29], it was not able to reduce ZIKV titers in Vero or C6/36 cells.…”

Section: Discussionmentioning

confidence: 99%

The Oxysterol 7-Ketocholesterol Reduces Zika Virus Titers in Vero Cells and Human Neurons

Willard

Elling

Stice

et al. 2018

Viruses

View full text Add to dashboard Cite

Zika virus (ZIKV) is an emerging flavivirus responsible for a major epidemic in the Americas beginning in 2015. ZIKV associated with maternal infection can lead to neurological disorders in newborns, including microcephaly. Although there is an abundance of research examining the neurotropism of ZIKV, we still do not completely understand the mechanism by which ZIKV targets neural cells or how to limit neural cell infection. Recent research suggests that flaviviruses, including ZIKV, may hijack the cellular autophagy pathway to benefit their replication. Therefore, we hypothesized that ZIKV replication would be impacted when infected cells were treated with compounds that target the autophagy pathway. We screened a library of 94 compounds known to affect autophagy in both mammalian and insect cell lines. A subset of compounds that inhibited ZIKV replication without affecting cellular viability were tested for their ability to limit ZIKV replication in human neurons. From this second screen, we identified one compound, 7-ketocholesterol (7-KC), which inhibited ZIKV replication in neurons without significantly affecting neuron viability. Interestingly, 7-KC induces autophagy, which would be hypothesized to increase ZIKV replication, yet it decreased virus production. Time-of-addition experiments suggest 7-KC inhibits ZIKV replication late in the replication cycle. While 7-KC did not inhibit RNA replication, it decreased the number of particles in the supernatant and the relative infectivity of the released particles, suggesting it interferes with particle budding, release from the host cell, and particle integrity.

show abstract

Section: Discussionmentioning

confidence: 99%

The Oxysterol 7-Ketocholesterol Reduces Zika Virus Titers in Vero Cells and Human Neurons

Willard

Elling

Stice

et al. 2018

Viruses

View full text Add to dashboard Cite

show abstract

“…Lastly, recent work suggests that the disaccharide 45 (trehalose) may prevent placental transmission of ZIKV by activating degradative autophagy. 127 F. Nucleoside Biosynthesis Inhibitors. One effective method to suppress rapidly replicating viruses is to decrease the level of available nucleoside pools.…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

Drugs for the Treatment of Zika Virus Infection

Bernatchez

Tran

et al. 2019

J. Med. Chem.

View full text Add to dashboard Cite

Zika virus is an emerging flavivirus that causes the neurodevelopmental congenital Zika syndrome and that has been linked to the neuroinflammatory Guillain–Barré syndrome. The absence of a vaccine or a clinically approved drug to treat the disease combined with the likelihood that another outbreak will occur in the future defines an unmet medical need. Several promising drug candidate molecules have been reported via repurposing studies, high-throughput compound library screening, and de novo design in the short span of a few years. Intense research activity in this area has occurred in response to the World Health Organization declaration of a Public Health Emergency of International Concern on February 1, 2016. In this Perspective, the authors review the emergence of Zika virus, the biology of its replication, targets for therapeutic intervention, target product profile, and current drug development initiatives.

show abstract

“…Trehalose, a simple plant based sugar known to modulate autophagy[ 49 50 ] is also a widely used ocular pharmaceutical agent that is used as an eye drop. It is known for its anti-viral properties, such as induction of type 1 interferons,[ 51 ] facilitating lysosomal degradation of intracellular virus,[ 52 ] reducing viral entry by decreasing the expression of host cell surface proteins that facilitates the attachment of virus to the cells[ 53 ] and reducing cathepsin activity [ Fig. 3 ].…”

Section: Ocular Mucosal Prophylaxismentioning

confidence: 99%

Potential ocular and systemic COVID-19 prophylaxis approaches for healthcare professionals

Shetty

Lalgudi

Khamar

et al. 2020

Indian J Ophthalmol

View full text Add to dashboard Cite

The COVID-19 pandemic has brought with it, innumerable challenges in healthcare, both through the direct burden of morbidity and mortality of the disease, and also by the curtailing of other essential albeit less emergency medical services to reduce the risk of community spread. Reports from around the world are showing mounting number of cases even in healthcare professionals spite of usage of adequate personal protective equipment. There are a number of factors which could account for this, be it the affinity of the virus to the respiratory and other mucosa or to patient risk factors for developing severe forms of the disease. In view of the growing need for resuming other medical services, it is essential to find newer ways to protect ourselves better, whether by systemic or topical mucosal prophylaxis with various medications or lifestyle changes promoting wellbeing and immunity. This article discusses additional prophylactic measures including drug repurposing or new indication paradigms to render protection. Certain medications such as chloroquine, trehalose, antihistaminics, and interferons used topically for various ocular conditions with reasonably good safety records are known to have anti-viral properties. Hence, can be harnessed in preventing SARS-CoV-2 attachment, entry, and/or replication in host cells. Similarly, use of hypertonic saline for nasal and oral mucosa and dietary changes are possible methods of improving our resistance. These additional prophylactic measures can be cautiously explored by healthcare professionals to protect themselves and their patients.

show abstract

Trehalose May Decrease the Transmission of Zika Virus to the Fetus by Activating Degradative Autophagy

Cited by 11 publications

References 49 publications

The Oxysterol 7-Ketocholesterol Reduces Zika Virus Titers in Vero Cells and Human Neurons

The Oxysterol 7-Ketocholesterol Reduces Zika Virus Titers in Vero Cells and Human Neurons

Drugs for the Treatment of Zika Virus Infection

Potential ocular and systemic COVID-19 prophylaxis approaches for healthcare professionals

Contact Info

Product

Resources

About