Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future

Abstract

Background: Noroviruses and rotaviruses are important viral etiologies of severe gastroenteritis. Noroviruses are the primary cause of nonbacterial diarrheal outbreaks in humans, whilst rotaviruses are a major cause of childhood diarrhea. Although both enteric pathogens substantially impact human health and economies, there are no approved drugs against noroviruses and rotaviruses so far. On the other hand, whilst the currently licensed rotavirus vaccines have been successfully implemented in over 100 countries, the most advanced norovirus vaccine has recently completed phase-I and II trials.Methods: We performed a structured search of bibliographic databases for peer-reviewed research litera-ture on advances in the fields of norovirus and rotavirus therapeutics and immunoprophylaxis.Results: Technological advances coupled with a proper understanding of viral morphology and replication over the past decade has facilitated pioneering research on therapeutics and immunoprophylaxis against noroviruses and rotaviruses, with promising outcomes in human clinical trials of some of the drugs and vaccines. This review focuses on the various developments in the fields of norovirus and rotavirus thera-peutics and immunoprophylaxis, such as potential antiviral drug molecules, passive immunotherapies (oral human immunoglobulins, egg yolk and bovine colostral antibodies, llama-derived nanobodies, and anti-bodies expressed in probiotics, plants, rice grains and insect larvae), immune system modulators, probiot-ics, phytochemicals and other biological substances such as bovine milk proteins, therapeutic nanoparti-cles, hydrogels and viscogens, conventional viral vaccines (live and inactivated whole virus vaccines), and genetically engineered viral vaccines (reassortant viral particles, virus-like particles (VLPs) and other sub-unit recombinant vaccines including multi-valent viral vaccines, edible plant vaccines, and encapsulated viral particles).Conclusions: This review provides important insights into the various approaches to therapeutics and im-munoprophylaxis against noroviruses and rotaviruses..

In Depth Breadth Analyses of Human Blockade Responses to Norovirus and Response to Vaccination

“…In addition to the effect on individual health, the worldwide economic burden of norovirus disease is estimated to be approximately 60 billion dollars per year [5]. As the understanding of the prevalence and burden of norovirus disease strengthens, the need for preventative and therapeutic measures becomes more apparent, including the development of an effective vaccine [6,7].…”

Codon optimization, expression in Escherichia coli, and immunogenicity analysis of deformed wing virus (DWV) structural protein

“…However, research on therapeutic drugs against DWV is still rare. Egg yolk antibodies known as immunoglobulin Y (IgY) have been widely utilized in the prevention and control of epidemic diseases associated with Acinetobacter baumannii, Vibrio splendidus, the Dengue virus, noroviruses, rotaviruses and duck adenovirus 3 (Fink et al, 2017;Ghosh, Malik & Kobayashi, 2017;Jahangiri et al, 2019;Li et al, 2016;Yin et al, 2019). Moreover, Sun et al (2018) reported that specific IgY could be obtained from hens immunized with an inactivated Chinese Sacbrood virus (CSBV) vaccine, which has the ability to neutralize CSBV.…”

Lactic Acid Bacteria as a Live Delivery System for the in situ Production of Nanobodies in the Human Gastrointestinal Tract

“…Some have been designed to block the entry of viruses into the host cells by targeting the viral envelope proteins, while others target essential intracellular viral proteins (Wu et al., 2017). These agents have shown a particular promise against rotavirus and norovirus (Ghosh et al., 2018), the most common causes of severe acute gastroenteritis in children (Riera-Montes et al., 2017). Several VHH generated against Group A rotavirus (RVA) strains were shown to neutralize rotavirus in vitro and provided different degrees of in vivo passive protection against rotavirus challenge when orally administered in a neonatal mouse model (van der Vaart et al., 2006; Garaicoechea et al., 2008; Gómez-Sebastián et al., 2012; Tokuhara et al., 2013; Maffey et al., 2015).…”