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Repurpose, Reuse, Rediscover Drugs for COVID-19 Treatments

COVID-19 is a difficult disease to understand and treat. Using drugs that are already on the market was the quickest path forward to evaluate these compounds and possibly help patients now because novel drug development typically takes years. Scientists needed to evaluate the field of potential drugs-and fast.

When a research team at the National Center for Advancing Translational Sciences (NCATS), an institute within the NIH, was tasked to help find a possible therapeutic, they decided on a drug repurposing strategy. One goal of the initial screen was to assess therapeutic inhibition of the SARS-CoV-2 spike protein (S1) binding to its angiotensin-converting enzyme (ACE2) receptor protein.

ACE2 is a common, vital receptor in the human body. It influences blood flow and is involved in many organs. It is particularly prevalent on cells that line the air sacs in lungs, hence the rampaging respiratory effects we’ve come to associate with the virus. It is, therefore, a tricky target for drugs.

In a matter of just a few months, the NCATS team was able to screen 3,384 molecular entities and narrow them down to a field of 25 quality “hits” capable of disrupting SARS-CoV-2 S1 protein:ACE2 receptor binding.

PerkinElmer’s AlphaLISA® Technology was the easy choice for this protein:protein interaction application.

A highly sensitive proximity assay, AlphaLISA can quickly and accurately determine which therapeutics are successful at interrupting the ACE2:S1 protein-protein interaction that leads to SARS-CoV-2 infection, the cause of COVID-19 symptoms.

AlphaLISA assay technology can be used in small molecule discovery but can also be applied to large molecule discovery, including biologics, vaccines and cell-based therapies. Concerns about a molecular therapeutic or target being too large are eliminated. Fears about losing the luminescent signal due to distance constraints are alleviated. The sheer number of toolbox reagents and kits available allow you to design your assay to minimize interactions with potential contaminants. It results in a homogenous no-wash, sensitive, and robust assay platform.

The next focus for the team is to identify similar small molecules to the 25 hits they uncovered and then try to improve the potency of each.

Read more about how the team leveraged this technology to help the pharma industry drive towards an effective treatment for COVID-19.

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