Understanding the Most Dangerous Aspects of COVID-19
Lee Makowski, Chair of the Department of Bioengineering at Northeastern University, has published a perspective article in the journal Virus titled, “Biological and Clinical Consequences of Integrin Binding via a Rogue RGD Motif in the SARS CoV-2 Spike Protein.” The article puts forth a hypothesis on the most dangerous aspects of COVID-19.
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GENERAL AUDIENCE:
One of the great mysteries of COVID-19 is how a coronavirus, known for causing mild respiratory disease, can be responsible for the wide array of puzzling symptoms that, in severe cases, impact many organs in the body, threatening the life of the patient. Professor Lee Makowski, his student Will Olson-Sidford and collaborator from U. Penn, John Weisel have put forth a theory with the potential to explain at least some of the most dangerous clinical aspects of COVID-19. It is well known that the virus enters cells of the respiratory tract by binding to a cell surface receptor known as ACE2. But the viral spike protein has evolved a structural motif that is used by many human viruses as a key to enter cells using a different class of receptors known as integrins. Integrins are present in virtually all organs of the body and control many cellular signaling pathways. Viral dysregulation of these pathways has the potential for triggering uncontrolled clotting disorders and disruption and damage to lung tissue and other organs including the heart and kidneys – disruption commonly seen in the most severe COVID-19 cases. Makowski and his colleagues make the case that their hypothesis needs to be tested since a better understanding of the origin of severe symptoms will greatly aid the development of strategies that could mitigate the worst aspects of severe COVID-19.
TECHNICAL AUDIENCE:
One of the great mysteries of COVID-19 is how a coronavirus, known for causing mild respiratory disease, can be responsible for the wide array of puzzling symptoms that, in severe cases, impact many organs in the body, threatening the life of the patient. Makowski et al (2021) put forth a theory with the potential to explain at least some of the most dangerous clinical aspects of COVID-19. It is well known that the virus enters cells of the respiratory tract by binding to the ACE2 receptor. But the viral spike protein has evolved an RGD structural motif that is used by many human viruses as a key to enter cells by binding to integrins. Integrins are present in virtually all organs of the body and control many cellular signaling pathways. Viral dysregulation of these pathways has the potential for triggering uncontrolled clotting disorders and disruption and damage to lung tissue and other organs including the heart and kidneys – issues commonly seen in the most severe COVID-19 cases. Makowski and his colleagues make the case that experiments to determine the potential for spike protein – integrin interactions should be carried out to test this hypothesis since a better understanding of the origin of severe symptoms will be critical for developing strategies that could mitigate the worst aspects of severe COVID-19.