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Repurposing Drugs To Treat COVID-19 – Benefits and Challenges

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Whilst scientists work tirelessly to develop an effective COVID-19 vaccine as a long-term preventive strategy, in parallel, researchers are also exploring the therapeutic potential of existing drugs as an efficient immediate approach.

We recently had the pleasure of speaking with Alan Fletcher, VP/GM, Life Sciences at PerkinElmer, Inc. to learn about the benefits and challenges of repurposing a drug in this context. Alan also touches on how informatics and artificial intelligence approaches can help unlock and reanalyze large amounts of data, and how it is possible to streamline the study of existing drugs and the investigation of viral infection life cycles by harnessing existing testing and analysis workflow solutions.

Q: There is considerable coverage around vaccine development for COVID-19, however this can take a considerable amount of time – both development of and access to the vaccine – in the meantime, there may be potential to repurpose existing drugs. Can you explain how companies go about this?

A:
As you know the average drug takes 10 to 12 years to bring to market, during which time pharma companies generate huge amounts of research insights and data that offer a critical window into how a drug will work in the human body. By tapping back into the that data and retesting for new conditions, diseases or viruses, repurposed drugs may be able to be accelerated.

There are a number of technologies and approaches that can come into play here.

On the data front, informatics and artificial intelligence (AI) can help unlock and reanalyze large amounts of data gathered from existing R&D and clinical trial data (for both approved and shelved drugs). As this data can be siloed in various formats, types, even locations, however, it will take time, effort and expertise to bring it together – but at least labs are not starting from scratch.

Existing available testing and analysis workflow solutions can also help enable more streamlined workflows for studying and deciphering viral infection life cycles for potential repurposing of drugs and doing discovery against potential new drugs and vaccines. LC/MS/MS and molecular spectroscopy technologies, for example, can be used in the preclinical development stages and to analyze drug metabolism and protein characterization; high-throughput screening and imaging platforms can help determine host-pathogen interactions and do compound screens; automation and robotics can help with sample preparation and extraction.

Q: As these drugs have already gained regulatory approval for other indications – would this accelerate their clinical development in COVID-19? How feasible is the approach(es.)?

A:
The ability to leverage past data and do new R&D with available testing and analysis solutions can significantly assist in considering a drug for use against new targets. We’ve seen it before from drugs fighting areas like cancer, for example. How that will play out specifically for COVID-19 as a novel virus we can’t predict, but these approaches and tools have helped in other instances and so we think they can play a strong role in the science being done to help fight COVID-19 in labs around the world. In the absence of the ability to bring a drug through the full clinical process, the FDA or other regulatory agencies around the world can grant designations for compassionate or emergency use. Having data readily available regarding an existing drug’s ability to target a virus via informatics etc. is critical to enable regulatory agencies to make those decisions.

Q: What are the challenges when looking to repurpose drugs?

A:
When repurposing a drug, one of the biggest challenges is to aggregate, search and analyze the vast amount of previously captured data to make efficient and effective use against a new indication. The holy grail is to know exactly how the drug blocks or prevents a mechanism of action that a virus might use. If you know that this drug blocks the mechanism of action used by COVID-19, you may have a candidate to consider. Again, informatics and AI, along with strong scientific data management expertise to bring it together, can assist here.

From a R&D testing and analysis solutions standpoint, challenges can include throughput and sample speed issues, as well as having technologies that span across the entire research workflow from the molecular up through drug QA/QC.

Q: How is PerkinElmer helping pharma overcome these challenges?

A:
For research purposes only – including around new drugs and vaccines or existing drugs for potential repurposing – PerkinElmer provides a variety of technologies and solutions that span from the molecular level
in target identification and characterization through manufacturing and QA/QC, including data management, analysis and visualization. Our informatics solutions (e.g. PerkinElmer Signals Medical Review and TIBCO Spotfire®) and our informatics services expertise assist pharma and research labs with tapping into and analyzing vast amounts of data so they can gain new insights. We offer robotic systems, such as the Janus® G3 and Sciclone® G3, as well as Chemagic 360 with integrable isolation kits for automating sample prep and extraction of nucleic acids from viruses, other pathogens and complex matrices for studies at the genomic and proteomic level. For subsequent detection and characterization of viral proteins and host immune markers, PerkinElmer also provides high throughput screening solutions such as the multimode readers (e.g., EnVision®, EnSight®, and Victor® Nivo) with Alpha, DELFIA®, and HTRF® biomarker reagent kits. To further understand the pathogenesis of viral infection and immune host response, our high content cellular imaging platforms (e.g., the Opera Phenix or Operetta CLS) and in vivo imaging systems such as the optical imaging IVIS® Lumina and IVIS® Spectrum and the Micro-CT Quantum GX2 systems enable the visualization and characterization of host factors involved in host–pathogen interactions and help with compound screens for drug discovery and development. Our triple quadrupole LC/MS/MS ( the QSight®series) and molecular spectroscopy UV and IR solutions (the LAMBA, Spectrum and Spectrum Spotlight systems) can be used in the preclinical development stage to analyze drug metabolism and protein characterization as well as during material characterization in manufacturing and QA/QC workflows.

Further, our
OneSource service teams continue to help Pharma’s critical lab instruments and software assets stay up and running during these challenging times as they work on existing or potentially new drugs.

Alan Fletcher was speaking to Molly Campbell and Laura Elizabeth Lansdowne, Science Writers for Technology Networks.