Prasad, H (2021) Protons to Patients: targeting endosomal Na+/H+ exchangers against COVID-19 and other viral diseases. In: FEBS Journal, 288 (17). pp. 5071-5088.
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Abstract
While there is undeniable evidence to link endosomal acid-base homeostasis to viral pathogenesis, the lack of druggable molecular targets has hindered translation from bench to bedside. The recent identification of variants in the interferon-inducible endosomal Na+/H+ exchanger 9 associated with severe coronavirus disease-19 (COVID-19) has brought a shift in the way we envision aberrant endosomal acidification. Is it linked to an increased susceptibility to viral infection or a propensity to develop critical illness? This review summarizes the genetic and cellular evidence linking endosomal Na+/H+ exchangers and viral diseases to suggest how they can act as a broad-spectrum modulator of viral infection and downstream pathophysiology. The review also presents novel insights supporting the complex role of endosomal acid-base homeostasis in viral pathogenesis and discusses the potential causes for negative outcomes of clinical trials utilizing alkalinizing drugs as therapies for COVID-19. These findings lead to a pathogenic model of viral disease that predicts that nonspecific targeting of endosomal pH might fail, even if administered early on, and suggests that endosomal Na+/H+ exchangers may regulate key host antiviral defence mechanisms and mediators that act to drive inflammatory organ injury. © 2021 Federation of European Biochemical Societies
| Item Type: | Journal Article |
|---|---|
| Publication: | FEBS Journal |
| Publisher: | John Wiley and Sons Inc |
| Additional Information: | The copyright for this article belongs to Author |
| Department/Centre: | Division of Biological Sciences > Molecular Reproduction, Development & Genetics |
| Date Deposited: | 03 Dec 2021 07:15 |
| Last Modified: | 03 Dec 2021 07:15 |
| URI: | http://eprints.iisc.ac.in/id/eprint/70146 |
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