COVID-19 and Diarylamidines: The Parasitic Connection

As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments h...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-04, Vol.24 (7), p.6583
Main Author: Hulme, John
Format: Article
Language:English
Subjects:
ACE2
Angiotensin
Angiotensin-converting enzyme 2
Bats
Binding
Combinatorial analysis
Complications
Coronaviruses
COVID-19
diarylamidines
Epigenetics
Humans
Immunotherapy
Long COVID
Membrane proteins
Monoclonal antibodies
Parasites
Parasitic diseases
Pentamidine isethionate
Peptidyl-dipeptidase A
Peptidyl-Dipeptidase A - metabolism
Post-Acute COVID-19 Syndrome
Proteases
Protein binding
Proteins
Protozoa
Renin
Renin-Angiotensin System
Review
SARS-CoV-2 - metabolism
serine protease
Serine proteinase
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Spike protein
Vaccine efficacy
Vaccines
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Summary:As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of "post-COVID-19 syndrome" and associated sequelae remain in their infancy, particularly as no established criteria for diagnosis currently exist. Thus, alternative therapies that reduce infection and prevent the broad range of symptoms associated with 'post-COVID-19 syndrome' require investigation. This review begins with an overview of the parasitic-diarylamidine connection, followed by the renin-angiotensin system (RAS) and associated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSSR2) involved in SARS-CoV-2 infection. Subsequently, the ability of diarylamidines to inhibit S-protein binding and various membrane serine proteases associated with SARS-CoV-2 and parasitic infections are discussed. Finally, the roles of diarylamidines (primarily DIZE) in vaccine efficacy, epigenetics, and the potential amelioration of long COVID sequelae are highlighted.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24076583