RT Journal Article
SR Electronic
T1 Pathophysiology and Potential Future Therapeutic Targets using Preclinical Models of COVID-19
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00405-2020
DO 10.1183/23120541.00405-2020
A1 Rahul Kumar
A1 Michael H. Lee
A1 Claudia Mickael
A1 Biruk Kassa
A1 Qadar Pasha
A1 Rubin Tuder
A1 Brian Graham
YR 2020
UL http://openres.ersjournals.com/content/early/2020/10/29/23120541.00405-2020.abstract
AB Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) gains entry into the lung epithelial cells by binding to the surface protein angiotensin-converting enzyme 2. Severe SARS-CoV-2 infection, also known as coronavirus disease 2019 (COVID-19), can lead to death due to acute respiratory distress syndrome mediated by inflammatory immune cells and cytokines. In this review, we discuss the molecular and biochemical bases of the interaction between SARS-CoV-2 and human cells, and in doing so we highlight knowledge gaps currently precluding development of new effective therapies. In particular, discovery of novel treatment targets in COVID-19 will start from understanding pathologic changes based on a large number of autopsy lung tissue samples. Pathogenetic roles of potential molecular targets identified in human lung tissues must be validated in established animal models. Overall, this stepwise approach will enable appropriate selection of candidate therapeutic modalities targeting SARS-CoV2 and the host inflammatory response.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Kumar reports grants from American Heart Association, grants from ATS Foundation/Pulmonary Hypertension Association, during the conduct of the study.Conflict of interest: Dr. Lee has nothing to disclose.Conflict of interest: Dr. Mickael has nothing to disclose.Conflict of interest: Dr. Kassa has nothing to disclose.Conflict of interest: Dr. Pasha has nothing to disclose.Conflict of interest: Dr. Tuder has nothing to disclose.Conflict of interest: Dr. Graham reports grants from National Institutes of Health, during the conduct of the study.