Advancements in organs-on-chips technology for viral disease and anti-viral research

Disease models that can accurately recapitulate human pathophysiology during infection and clinical response to antiviral therapeutics are still lacking, which represents a major barrier in drug development. The emergence of human Organs-on-a-Chip that integrated microfluidics with three-dimensional (3D) cell culture, may become the potential solution for this urgent need. Human Organs-on-a-Chip aims to recapitulate human pathophysiology by incorporating tissue-relevant cell types and their microenvironment, such as dynamic fluid flow, mechanical cues, tissue–tissue interfaces, and immune cells to increase the predictive validity of in vitro experimental models. Human Organs-on-a-Chip has a broad range of potential applications in basic biomedical research, preclinical drug development, and personalized medicine. This review focuses on its use in the fields of virology and infectious diseases. We reviewed various types of human Organs-on-a-Chip-based viral infection models and their application in studying viral life cycle, pathogenesis, virus-host interaction, and drug responses to virus- and host-targeted therapies. We conclude by proposing challenges and future research avenues for leveraging this promising technology to prepare for future pandemics.

Triterpenoid-Mediated Inhibition of Virus-Host Interaction: Is Now the Time for Discovering Viral Entry/Release Inhibitors from Nature?

Fatal infectious diseases caused by HIV-1, influenza A virus, Ebola virus, and currently pandemic coronavirus highlight the great need for the discovery of antiviral agents in mechanisms different from current viral replication-targeted approaches. Given the critical role of virus-host interactions in the viral life cycle, the development of entry or shedding inhibitors may expand the current repertoire of antiviral agents; the combination of antireplication inhibitors and entry or shedding inhibitors would create a multifaceted drug cocktail with a tandem antiviral mechanism. Therefore, we provide critical information about triterpenoids as potential antiviral agents targeting entry and release, focusing specifically on the emerging aspect of triterpenoid-mediated inhibition of a variety of virus-host membrane fusion mechanisms via a trimer-of-hairpin motif. These properties of triterpenoids supply their host an evolutionary advantage for chemical defense and may protect against an increasingly diverse array of viruses infecting mammals, providing a direction for antiviral drug discovery.