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Inhibition of SARS-CoV-2 Viral Channel Activity Using FDA-Approved Channel Modulators Independent of Variants.
Yu, Han-Gang; Sizemore, Gina; Martinez, Ivan; Perrotta, Peter.
  • Yu HG; Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
  • Sizemore G; Clinical Medicine Resources, EZCARE Walk-in Medical Center, Moorefield, WV 26836, USA.
  • Martinez I; Department of Microbiology, Immunology, & Cell Biology, Cancer Institute, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
  • Perrotta P; Anatomy & Laboratory Medicine, Department of Pathology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
Biomolecules ; 12(11)2022 11 11.
Article in English | MEDLINE | ID: covidwho-2109923
ABSTRACT

BACKGROUND:

SARS-CoV-2 has undergone mutations, yielding clinically relevant variants.

HYPOTHESIS:

We hypothesized that in SARS-CoV-2, two highly conserved Orf3a and E channels directly related to the virus replication were a target for the detection and inhibition of the viral replication, independent of the variant, using FDA-approved ion channel modulators.

METHODS:

A combination of a fluorescence potassium ion assay with channel modulators was developed to detect SARS-CoV-2 Orf3a/E channel activity. Two FDA-approved drugs, amantadine (an antiviral) and amitriptyline (an antidepressant), which are ion channel blockers, were tested as to whether they inhibited Orf3a/E channel activity in isolated virus variants and in nasal swab samples from COVID-19 patients. The variants were confirmed by PCR sequencing.

RESULTS:

In isolated SARS-CoV-2 Alpha, Beta, and Delta variants, the channel activity of Orf3a/E was detected and inhibited by emodin and gliclazide (IC50 = 0.42 mM). In the Delta swab samples, amitriptyline and amantadine inhibited the channel activity of viral proteins, with IC50 values of 0.73 mM and 1.11 mM, respectively. In the Omicron swab samples, amitriptyline inhibited the channel activity, with an IC50 of 0.76 mM.

CONCLUSIONS:

We developed an efficient method to screen FDA-approved ion channel modulators that could be repurposed to detect and inhibit SARS-CoV-2 viral replication, independent of variants.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment / Ion Channels Type of study: Diagnostic study / Prognostic study Topics: Traditional medicine / Variants Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Biom12111673

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment / Ion Channels Type of study: Diagnostic study / Prognostic study Topics: Traditional medicine / Variants Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Biom12111673