The SARS-CoV-2 pandemic is not the first dire demonstration of the huge impact virology can have on our life. Preceding outbreaks like the Spanish flu and Ebola have already established the importance of antiviral drug discovery and research.
Viruses are infectious particles that range from 16 nm to 300 nm in size. They depend on host cells in order to replicate their genetic material (which can be either DNA or RNA) as well as other viral components and are thus classified as intracellular parasites.
The infectious cycle can be separated into four steps:
Entry, Replication, Assembly, and Release.
The cycle starts with the binding of the virus to specific receptor molecules on the plasma membrane of the host cell. Afterwards, the virus is taken up by the cell, often in an endocytosis-mediated process. In order to evade the destruction in the endosome, viruses use versatile mechanisms to get released into the cytoplasm. Enveloped viruses like SARS-CoV-2 or influenza viruses express specific fusion peptides, which facilitate the fusion of their membrane with the endosome membrane, thereby initiating the release of the viral nucleocapsid into the cytoplasm.
Next, viral genes are replicated and viral components are synthesized by the cellular machinery. Some viruses include their own polymerases or reverse transcriptases for replication. However, all viruses depend on the cellular translation machinery. Finally, all components self-assemble into new viral particles, which exit the cell.
Currently, there is a lack of anti-viral drugs. To develop new compounds, detailed knowledge of the virus is needed. Possible targets of compounds include viral entry and fusion, replication, proteolytic processing, and particle egress. Instead of targeting viral proteins, drugs can alternatively act on the cellular pathways hijacked by the virus. This strategy is less virus-specific and thus reduces the risk for drug resistance. On the other hand, it can increase adverse effects.
The switchSENSE® technology is especially suitable for investigating viral replication. You can easily investigate the activity of viral polymerases/transcriptases and screen inhibitors. Furthermore, you can examine anti-viral antibodies and measure interactions of viral particles with cellular receptors — soon directly on cells!
Directly measure the interaction of viruses with cells I stay tuned – coming fall/winter 2022!
→ Measuring Influenza A Virus and Peptide Interaction Using Electrically Controllable DNA Nanolevers
2021 I Advanced Materials Technologies (open access)
→ Biophysical Studies of the Binding of Viral RNA with the 80S Ribosome Using switchSENSE
2021 I Methods in Molecular Biology book series (MIMB, volume 2263)
→ Polymerase/DNA interactions and enzymatic activity: multi-parameter analysis with electro-switchable biosurfaces
2015 I Scientific Reports (open access)
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