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Phenomics – Strategy for antiviral drug repurposing or discovery
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Phenomics – Strategy for antiviral drug repurposing or discovery

bioxone August 4, 2021August 3, 2021

Monika Raman, PSG College of Technology, Coimbatore

The advent of the current COVID-19 pandemic and its ongoing worldwide spread has emphasized the necessity for quickly and efficiently identifying novel or recurrent medicinal medicines. 

Even though antiviral drug findings are available, the majority prefer to concentrate on the effects of such medications on a particular virus, its component proteins, or its enzyme, often disregarding the impacts on host cells. The effectiveness of these antiviral compounds may be assessed partially since the possible toxicity that affects host cell physiology might conceal both virus and drug applicants’ effects. 

Host-orientation and combination therapy might therefore be useful in the fight against the current and future viral epidemics. Therefore, it is necessary to employ novel ways of profiling – cellular responses during infection with the virus, which may be exploited for drugs. 

Researchers from Uppsala University, Sweden, have therefore proposed a new approach. A technique for evaluating the overall health of host cells based on morphological profiling for non-target testing of viral infections.

Phenomics approach

Jonne Rietdijk, the author of this work, said: “We present a new method Phenomics, that combines morphological profiling with antibody-based detection of viral infection in a single experiment”. They tested it on CoV-229E-infected MRC-5 primary lung fibroblasts in the absence and presence of several new antiviral agents. 

They built an automated image analysis pipeline, generating hundreds of morphological measures – to distinguish infected and non-infected cells. These measures are produced to examine the biology of host cells on a single-cell level. 

The resultant morphology profiles were utilized to capture a phenotype signature generated by the virus. This profile may be used to filter the cell phenotype from an infected cell to a non-infected state for antivirals. Morphological characteristics may also be utilized to detect the MoA of new antiviral drugs.

Can we identify antiviral drugs against SARS-CoV-2 through Phenomics?

Due to relatively poor pathogenicity, they took advantage of CoV-229E, which allowed experiments in the BSL2 laboratory. It is also extensively used in studying the pathogenesis of coronavirus, the replication cycle, and interactions amongst host viruses. 

“However, Remdesivir and E64d have also been reported to successfully inhibit SARS-CoV-2 infection in cultured cells, comparable to our results for CoV-229E infection,” Marianna Tampere, co-author of this study, stated. Their findings suggest that their technique can also be utilized to find antiviral medicines for SARS-CoV-2.

Phenomics – Novel strategy for drug discovery

This innovative phenomics technique may be utilized to morphologically profile viral infection on host cells in an unbiased manner. Antiviral reference compounds, as well as new antivirals, can be identified using this technique. This indicates its potential for use as an antiviral drug repurposing and drug discovery method.

Their groundbreaking phenomics technique provides an untargeted readout for antiviral medication screening at the single-cell level and in a single assay. Novel compounds’ potential MoA may be determined by comparing them to those of annotated reference medicines, emphasizing the utility of this technique in drug development. 

Morphological profiling has a wide range of flexibility and scalability, making it ideal for studying various cell lines and perturbations. As a result, with just minimal changes to the image analysis pipeline, this untargeted method will enable numerous applications utilizing a variety of cell lines and viruses. Overall, the phenomics method may be used to conduct impartial research on virus-induced effects on host cells, which can be used for therapeutic repurposing and the development of new antiviral drugs.

Also read: Nanoparticles to treat a common type of cancer- neuroblastoma

Reference: Rietdijk, J., Tampere, M., Pettke, A., Georgiev, P., Lapins, M., Warpman-Berglund, U., Spjuth, O., Puumalainen, M.-R., & Carreras-Puigvert, J. (2021). A phenomics approach for antiviral drug discovery. BMC Biology, 19(1), 156. https://doi.org/10.1186/s12915-021-01086-1

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About the author:

Monika Raman is an undergraduate student pursuing her final year B. Tech in Biotechnology. She is an enthusiastic Biotech student aspiring for an opportunity to develop skills and grow professionally in the research field. Extremely motivated and possess strong interpersonal skills.

Read some of her published articles at BioXone:

  • Targeting viral protein ORF3a to fight Covid-19! – BioXone
  • Are the unvaccinated a threat to the vaccinated? – BioXone
  • Mynvax raises $4.2M to develop ‘thermostable’ Covid-vaccine – BioXone
  • Respiratory syncytial virus: Understanding its different aspects – BioXone

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Tagged antibody-based detection antiviral drug Cell Painting CoV-229E drug discovery Drug Repurposing Morphological profiling Phenomics SARS-CoV-2 Single assay

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