Abstract
Acute gastroenteritis caused by virus has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The main culprits are rotaviruses, noroviruses, sapoviruses, astroviruses, and enteric adenoviruses. Currently, there are no antiviral drugs available for the prevention or treatment of viral gastroenteritis. Here, we describe the antivirals that were identified as having in vitro and/or in vivo activity against these viruses, originating from in silico design or library screening, natural sources or being repurposed drugs. We also highlight recent advances in model systems available for this (hard to cultivate) group of viruses, such as organoid technologies, and that will facilitate antiviral studies as well as fill some of current knowledge gaps that hamper the development of highly efficient therapies against gastroenteric viruses.
Highlights
Diarrheal diseases have an estimate of 1.7 billion episodes of acute diarrhea annually, being one of the leading causes of mortality in children up to five years of age worldwide [1,2,3,4]
Viral gastroenteritis is the main cause of such diarrhea and is caused by several viruses, including human rotaviruses (HRVs), noroviruses (HuNoVs), sapoviruses (HuSaVs), astroviruses (HAstV), and enteric adenoviruses (HAdVs) [5]
The transcription of the RV genome can be directly inhibited by targeting the VP1, RNA dependent-RNA polymerase (RdRp), using 20 -C-methyl nucleosides such as 7-deaza20 -C-methyladenosine (7DMA) and 20 -C-methylcytidine (2CMC) [40]
Summary
Diarrheal diseases have an estimate of 1.7 billion episodes of acute diarrhea annually, being one of the leading causes of mortality in children up to five years of age worldwide [1,2,3,4]. Viral gastroenteritis is the main cause of such diarrhea and is caused by several viruses, including human rotaviruses (HRVs), noroviruses (HuNoVs), sapoviruses (HuSaVs), astroviruses (HAstV), and enteric adenoviruses (HAdVs) [5]. These viruses have a worldwide distribution and most commonly infect children, while HuNoV infects all age groups. The preponderance of poor absorption, inflammation, and secretory diarrhea is not well understood, nor is the mechanism underlying virus-induced emesis since rodents are not adequate to study this hallmark of disease as they lack the vomiting reflex All of these viruses have strains that replicate in animals, revealing a broad host range and potential to cross species barriers [30], highlighting the possibility of zoonotic transmission. The poor understanding of diarrhea-causing viruses and high prevalence of these infections call for improved in vitro and in vivo models to study these viruses in order to develop efficient antiviral strategies
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