Monoclonal antibodies and fibrates are two examples of emerging treatments that have demonstrated potential for treating patients infected with COVID-19. Both treatments work in the same basic way, by targeting coronavirus’s distinctive protein spikes and neutralizing their ability to bind to healthy human cells. This action of combating coronavirus infection has shown great promise in both lab and clinical settings.
However, antibody treatment can be costly. For that reason, discovering new anti-COVID agents remains a top priority for the medical research community. The search for new candidates that can bind—and interfere—with COVID-19 spike proteins has been greatly expedited through the use of advanced protein stabilization assays. Recent studies using these assays have shown that a similar mechanism of battling SARS-CoV-2 might be achieved without intravenous injections. In fact, new treatments may be possible without the need to even swallow a pill—therapy may instead involve a topical medication like an ointment, salve, or patch.
Differential Scanning Fluorimetry
Differential scanning fluorimetry (DSF) is a screening process that is used to investigate proteins, their structures, and their behaviors such as their folding and unfolding. DSF testing is sometimes referred to as a thermal shift assay, and it uses a series of dyes to observe the interaction and progressive denaturing of a protein. The denaturation is controlled through the application of heat.
The study of denaturation, folding, and unfolding is crucial to understanding both the means by which proteins change and the effect the changes have on their function. In particular, the way a protein’s long chains of amino acids fold creates a distinct structure—the binding sites left exposed on the protein’s surface are critical to allow the protein to interact with other molecules within the body. These changes can alter how a particular protein—including a spike protein on the SARS-CoV-2 virus—interacts with other molecules.
In order to accurately measure spike protein interactions, sensitivity, accuracy and precision make a difference. When it comes to biologics stability, characterization tools like Prometheus offer precise stability data to characterize thermal folding and aggregation of proteins.
Human Neutrophil Peptide 1 (HNP1)
Human Neutrophil Peptide 1, or HNP1, is a special antimicrobial molecule called a defensin. Defensins are immunomodulatory agents and play a significant role in regulating healthy immune system responses. Studies using differential scanning fluorimetry revealed that both HNP1 and RC-101, another type of defensin called a retrocyclin, can destabilize SARS-CoV-2 spike proteins and thus limit their ability to infect human cells.
It was found that HNP1 was able to bind directly to recombinant spike protein structures. Its affinity was characterized, and the results highlighted HNP1’s highly selective targeting of viral spike proteins. Alteration of these spike proteins—including those that give coronaviruses their eponymous spiky crown structure—provides an effective way to prevent further infections.
Topical Medications for SARS-CoV-2
RC-101 has been used in topical medications to treat HIV, leading researchers to hope a similar medication could be developed for the treatment of COVID-19. Moving forward, researchers believe defensins—retrocyclins in particular—have a great deal of potential as widespread anti-viral treatments for COVID-19 and similar diseases. They are highly stable, low in toxicity and side effects, and resistant to degradation. If successful, researchers hope to develop topical substances to prevent and treat coronaviruses like COVID-19, in addition to other yet-unknown viruses.
Sources:
https://www.clinicaltrialsarena.com/news/study-fenofibrate-covid-infection/
https://www.news-medical.net/news/20210531/Researchers-identify-defensins-as-potential-anti-SARS-CoV-2-agents.aspx
https://www.sciencedirect.com/science/article/pii/S0022283621004587
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002491
https://www.nature.com/articles/srep05625
https://www.biorxiv.org/content/10.1101/2021.05.27.445985v1
