Protons to Patients: targeting endosomal Na+ /H+ exchangers against COVID-19 and other viral diseases.
FEBS J
; 288(17): 5071-5088, 2021 Sep.
Article
in English
| MEDLINE | ID: covidwho-1393880
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Diseases
/
Sodium-Hydrogen Exchangers
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
FEBS J
Journal subject:
Biochemistry
Year:
2021
Document Type:
Article
Affiliation country:
Febs.16163
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