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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Pathophysiology and potential future therapeutic targets using preclinical models of COVID-19
Rahul Kumar1, Michael H Lee1, Claudia Mickael2
1Dept of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, USA.
Abstract:
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.
Insights
Understanding how SARS-CoV-2 infects lung cells is key to developing new COVID-19 therapies. Further research into pathological changes and molecular targets is needed for effective treatments.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) enters lung epithelial cells via angiotensin-converting enzyme 2.
- Severe coronavirus disease 2019 (COVID-19) can cause fatal acute respiratory distress syndrome due to inflammatory responses.
Purpose of the Study:
- To review the molecular and biochemical interactions between SARS-CoV-2 and human cells.
- To identify knowledge gaps hindering the development of effective COVID-19 therapies.
Main Methods:
- Review of existing literature on SARS-CoV-2 cellular entry and pathogenesis.
- Emphasis on the need for analysis of autopsy lung tissues to identify pathological changes.
- Highlighting the necessity of validating molecular targets in animal models.
Main Results:
- Current understanding of SARS-CoV-2-host interactions has limitations for therapeutic development.
- Autopsy lung tissue analysis is crucial for discovering novel COVID-19 treatment targets.
- Animal models are essential for validating the pathogenetic roles of identified targets.
Conclusions:
- A stepwise approach combining human tissue analysis and animal model validation is necessary.
- This approach will facilitate the selection of effective therapeutic strategies targeting both SARS-CoV-2 and the host inflammatory response.
- Addressing knowledge gaps is critical for advancing COVID-19 treatment options.
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