Pharma R&D Today
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Modulators, Biomarkers and Potential Treatments for COVID-19
Posted on May 14th, 2020 by Yapeng Zhang in COVID-19
With the trend of open science, people are becoming more receptive to the idea of sharing data and using what is already accessible. Particularly for researchers, there is so much data available that can answer questions and develop hypotheses and strategies that could save effort, time and money. This is mainly important in cases where rapid discoveries are required, such as in the case of the current COVID-19 outbreak.
Recently, a research group in China approached us to help answer four questions they had in mind concerning covid-19:
- Are there any key proteins used by Coronavirinae for entry and fusion into host cells, which could be common with the COVID-19 virus?
- Are there available inhibitors of the current COVID-19 receptor, ACE2, which could be used for potential drug screening?
- Are there any COVID-19 Spike protein inhibitors for potential drug screening?
- Are there any immune-modulators used in anti-virus therapies that could be potential drugs for Systemic Inflammatory Response Syndrome (SIRS), a major player in multiple-organ damage and malfunction during late-stage COVID-19 infection.
To address these questions, we used Elsevier Life Sciences solutions to retrieve literature, compounds, biological pathways and key information pertinent to these questions. Specifically, our team used Embase and Elsevier Text Mining tools to retrieve information from literature, at the sentence-evidence level, concerning coronaviruses entry/fusion proteins and their potential host cells. Reaxys was also used to identify potential ACE2 and Spike protein inhibitors that could be potentially used for drug screening. Finally, Embase, PharmaPendium, Pathway Studio and ETM were used to find potential inflammation pathways that could be associated with late-stage COVID-19 infection and the relevant immune-modulators that have been used for the treatment of viral infections.
Preliminary analysis of the retrieved information provided primary answers to the client’s four questions, which bring new insights into modulators, biomarkers and potential treatments for COVID-19 infection. Compared with other coronaviruses, COVID-19 has distinct spike proteins and four insertions in the spike glycoprotein gene that are critical for the virus to enter the target cells. Of importance, our data showed a huge difference not only in the inflammatory markers between COVID-19-infected patients and healthy individuals but also between Intensive care unit (ICU) patients and non-ICU patients.
Interestingly, non-survivors of 2019-nCoV infection showed a continuous increase in neutrophil count, D-dimer, blood urea, and creatinine levels and a continuous decrease in lymphocyte counts until death occurred. As for the pathophysiology, inhibition of ACE2 by COVID-19 infection may lead to the induction NADPH oxidase, and hence, to an increase in the production of Reactive Oxygen Species (ROS), major inflammatory mediators. Therefore, evidence from literature indicates that treatment of COVID-19-related injury could be achieved by balancing the renin-angiotensin system (RAS), a complex of alternative enzymatic pathways in which ACE2 plays a major role as an anti-inflammatory mediator1.
While this COVID-19 information package was particularly developed to answer these four specific questions, it can also be used to address other queries related to COVID-19 and other coronaviruses.
Feel free to contact me if you are performing research on coronaviruses and you are interested in this COVID-19 information package. I would also be happy to help you find answers to your specific research questions.
- Nehme, A., Zouein, F. A., Zayeri, Z. D. & Zibara, K. An Update on the Tissue Renin Angiotensin System and Its Role in Physiology and Pathology. J Cardiovasc Dev Dis 6, (2019).
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