These challenging times call for united social and corporate responsibilities, as well as meaningful actions, that can help mitigate and, ultimately, overcome the coronavirus global pandemic. As an innovative biotechnology company, AnaBios is focused on how drugs work in humans to treat and prevent diseases. The first critical step in tackling a disease is to understand how it develops in humans. For Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which causes COVID-19, the scientific insight is rapidly advancing as a result of significant effort by clinicians and scientists across the globe.
Nonetheless, there remains a tremendous level of uncertainty about the fundamental biology of this virus and the pathophysiology that results from the interaction between COVID-19 and various organs and tissues in the human body.
Respiratory complications are the primary cause of morbidity, with complex interactions between the virus, lung epithelial cells and immune cells, leading to SARS. Following its activation by the Transmembrane Serine Protease 2 (TMPRSS2), the attachment protein “spike” on the surface of the virus directly binds to the angiotensin converting enzyme 2 (ACE2) expressed on the epithelial lung cell surface, triggering the virus entry into the cell. ACE2 plays an important role in regulating the renin-angiotensin system (RAS); acting as a protease to cleave angiotensin II to angiotensin 1-7, ACE2 counteracts the effect of angiotensin II and diminishes vasoconstriction mediated by the RAS.
Early clinical reports have highlighted the high prevalence of cardiovascular disease among patients infected with COVID-192,3. Risk factors for severe complications include hypertension, congestive heart failure and atherosclerosis, conditions in which the ACE2 pathway can have a major impact; therefore, ACE2 and its variants may play a key role in the disease by both facilitating viral infections as well as creating underlying pathological states that predispose to serious complications.
This brings to light some of the many un-answered questions surrounding the pathological agent driving the current pandemic. While we see wide disparities in the outcome of infection in different patients, it is unclear how age, genetic variants, viral load and underlying conditions interact to affect the course of the disease. Does the expression level of ACE2 affect viral entry into the cell? How does the level of ACE2 expression change with age? Do blood pressure medications targeting the ACE pathway affect viral entry? Are there ACE2 variants that confer susceptibility to the infection? The answers to many of these questions could have important implications in the investigations that have already been started to develop antiviral drugs that can clinically prevent or treat coronavirus infections.
A high number of severe COVID-19 cases have also been linked to cardiac complications, including reduction in cardiac contractility, myocarditis, acute myocardial infarction, and exacerbation of heart failure. ACE2 is also expressed in the heart, providing access to coronaviruses to the cardiovascular system. In addition, human autopsy samples demonstrate that coronaviruses can down-regulate myocardial ACE2 leading to myocardial inflammation, cause cytokine storm and hypoxia-induced cardiac apoptosis. The exact details of these virus-mediated cardiac complications are yet to be determined.
AnaBios is partnering with researchers around the world, working with industry regulatory agencies, as well as academic research institutions. By enabling the utilization of high-quality human samples for functional studies of lung or cardiac physiology and pathophysiology, we can help scientists address key questions on the path to the development of efficacious treatments. Through examining a large range of human samples across age sets and underlying disease conditions, scientists can establish whether specific genetic variants and age-driven changes in molecular biology and physiology, underlie why some patients are at high risk of hospitalization and death while others only suffer mild symptoms.
This approach allows for the successful transition of drug discovery programs from the bench to the bed side and can rapidly advance human translational sciences. We welcome your inquiries on how AnaBios can support your coronavirus-focused research to help understand how the virus impacts the function of the lungs and the heart.
Lastly, we would like to acknowledge the importance of working safely in the laboratory. While remaining in operation, AnaBios complies with recent mandates to mitigate the spread of COVID-19.
1 Hoffmann et al. (2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. doi: 10.1016/j.cell.2020.02.052.
2 Zheng et al. (2020) COVID-19 and the cardiovascular system. Nature Reviews Cardiology, https://doi.org/10.1038/s41569-020-0360-5
3 Clerkin et al. (2020) Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease. Circulation, https://doi.org/10.1161/CIRCULATIONAHA.120.046941