Repurposing Polyether Ionophores As a New-Class of Anti-SARS-Cov-2 Agents As Adjunct Therapy

Overview

Journal Curr Microbiol

Specialty Microbiology

Date 2023 Jul 6

PMID 37414909

Authors

Keerthana Gurukkalot

Vinoth Rajendran

Affiliations

Soon will be listed here.

Abstract

The emergence of SARS-CoV-2 and its variants have posed a significant threat to humankind in tackling the viral spread. Furthermore, currently repurposed drugs and frontline antiviral agents have failed to cure severe ongoing infections effectively. This insufficiency has fuelled research for potent and safe therapeutic agents to treat COVID-19. Nonetheless, various vaccine candidates have displayed a differential efficacy and need for repetitive dosing. The FDA-approved polyether ionophore veterinary antibiotic for treating coccidiosis has been repurposed for treating SARS-CoV-2 infection (as shown by both in vitro and in vivo studies) and other deadly human viruses. Based on selectivity index values, ionophores display therapeutic effects at sub-nanomolar concentrations and exhibit selective killing ability. They act on different viral targets (structural and non-structural proteins), host-cell components leading to SARS-CoV-2 inhibition, and their activity is further enhanced by Zn supplementation. This review summarizes the anti-SARS-CoV-2 potential and molecular viral targets of selective ionophores like monensin, salinomycin, maduramicin, CP-80,219, nanchangmycin, narasin, X-206 and valinomycin. Ionophore combinations with Zn are a new therapeutic strategy that warrants further investigation for possible human benefits.

Citing Articles

SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK.

Bhattacharyya S, Tobacman J Signal Transduct Target Ther. 2024; 9(1):39.

PMID: 38355690 PMC: 10866996. DOI: 10.1038/s41392-024-01741-3.

References

Shaman J, Galanti M . Will SARS-CoV-2 become endemic?. Science. 2020; 370(6516):527-529. DOI: 10.1126/science.abe5960. View

Katzourakis A . COVID-19: endemic doesn't mean harmless. Nature. 2022; 601(7894):485. DOI: 10.1038/d41586-022-00155-x. View

Jacobs L, Gourna Paleoudis E, Lesky-Di Bari D, Nyirenda T, Friedman T, Gupta A . Persistence of symptoms and quality of life at 35 days after hospitalization for COVID-19 infection. PLoS One. 2020; 15(12):e0243882. PMC: 7732078. DOI: 10.1371/journal.pone.0243882. View

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395(10223):507-513. PMC: 7135076. DOI: 10.1016/S0140-6736(20)30211-7. View

Yu J, Collier A, Rowe M, Mardas F, Ventura J, Wan H . Neutralization of the SARS-CoV-2 Omicron BA.1 and BA.2 Variants. N Engl J Med. 2022; 386(16):1579-1580. PMC: 9006770. DOI: 10.1056/NEJMc2201849. View

Perez-Gomez R . The Development of SARS-CoV-2 Variants: The Gene Makes the Disease. J Dev Biol. 2021; 9(4). PMC: 8705434. DOI: 10.3390/jdb9040058. View

Tao K, Tzou P, Nouhin J, Gupta R, de Oliveira T, Kosakovsky Pond S . The biological and clinical significance of emerging SARS-CoV-2 variants. Nat Rev Genet. 2021; 22(12):757-773. PMC: 8447121. DOI: 10.1038/s41576-021-00408-x. View

Vkovski P, Kratzel A, Steiner S, Stalder H, Thiel V . Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2020; 19(3):155-170. PMC: 7592455. DOI: 10.1038/s41579-020-00468-6. View

Elfiky A . SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an perspective. J Biomol Struct Dyn. 2020; 39(9):3204-3212. PMC: 7222627. DOI: 10.1080/07391102.2020.1761882. View

10.

van Hemert M, van den Worm S, Knoops K, Mommaas A, Gorbalenya A, Snijder E . SARS-coronavirus replication/transcription complexes are membrane-protected and need a host factor for activity in vitro. PLoS Pathog. 2008; 4(5):e1000054. PMC: 2322833. DOI: 10.1371/journal.ppat.1000054. View

11.

Malik Y . Properties of Coronavirus and SARS-CoV-2. Malays J Pathol. 2020; 42(1):3-11. View

12.

Yadav R, Chaudhary J, Jain N, Kumar Chaudhary P, Khanra S, Dhamija P . Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19. Cells. 2021; 10(4). PMC: 8067447. DOI: 10.3390/cells10040821. View

13.

Singh T, Parida S, Lingaraju M, Kesavan M, Kumar D, Singh R . Drug repurposing approach to fight COVID-19. Pharmacol Rep. 2020; 72(6):1479-1508. PMC: 7474498. DOI: 10.1007/s43440-020-00155-6. View

14.

Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H . Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020; 6:16. PMC: 7078228. DOI: 10.1038/s41421-020-0156-0. View

15.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M . Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3):269-271. PMC: 7054408. DOI: 10.1038/s41422-020-0282-0. View

16.

Hoffmann M, Mosbauer K, Hofmann-Winkler H, Kaul A, Kleine-Weber H, Kruger N . Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2. Nature. 2020; 585(7826):588-590. DOI: 10.1038/s41586-020-2575-3. View

17.

Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G . Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020; 382(25):2411-2418. PMC: 7224609. DOI: 10.1056/NEJMoa2012410. View

18.

Magagnoli J, Narendran S, Pereira F, Cummings T, Hardin J, Sutton S . Outcomes of Hydroxychloroquine Usage in United States Veterans Hospitalized with COVID-19. Med. 2020; 1(1):114-127.e3. PMC: 7274588. DOI: 10.1016/j.medj.2020.06.001. View

19.

Altulea D, Maassen S, Baranov M, van den Bogaart G . What makes (hydroxy)chloroquine ineffective against COVID-19: insights from cell biology. J Mol Cell Biol. 2021; 13(3):175-184. PMC: 7989365. DOI: 10.1093/jmcb/mjab016. View

20.

Sisay M . Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19?. Front Pharmacol. 2020; 11:791. PMC: 7264155. DOI: 10.3389/fphar.2020.00791. View