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

被引:3
作者
Gurukkalot, Keerthana [1 ]
Rajendran, Vinoth [1 ]
机构
[1] Pondicherry Univ, Sch Life Sci, Dept Microbiol, Pondicherry 605014, India
关键词
Ionophores; SARS-CoV-2; Anti-virals; Co-infection; Zn2+; PLASMODIUM-FALCIPARUM; BROAD-SPECTRUM; GOLGI-COMPLEX; BREAST-CANCER; CELLS; CORONAVIRUS; MONENSIN; VALINOMYCIN; SALINOMYCIN; INHIBITION;
D O I
10.1007/s00284-023-03366-1
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 Zn2+ 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 Zn2+ are a new therapeutic strategy that warrants further investigation for possible human benefits.
引用
收藏
页数:14
相关论文
共 130 条
[31]  
Fiebich Katrin, 1999, Pesticide Science, V55, P379, DOI 10.1002/(SICI)1096-9063(199903)55:3<379::AID-PS919>3.0.CO
[32]  
2-M
[33]  
Fong C, 2021, HAL03347139V2
[34]  
Fong Clifford W., 2016, International Journal of Computational Biology and Drug Design, V9, P228, DOI 10.1504/IJCBDD.2016.078284
[35]  
Garcia C. C., 2007, Infectious Disorders - Drug Targets, V7, P204, DOI 10.2174/187152607782110004
[36]   SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals [J].
Gassen, Nils C. ;
Papies, Jan ;
Bajaj, Thomas ;
Emanuel, Jackson ;
Dethloff, Frederik ;
Chua, Robert Lorenz ;
Trimpert, Jakob ;
Heinemann, Nicolas ;
Niemeyer, Christine ;
Weege, Friderike ;
Hoenzke, Katja ;
Aschman, Tom ;
Heinz, Daniel E. ;
Weckmann, Katja ;
Ebert, Tim ;
Zellner, Andreas ;
Lennarz, Martina ;
Wyler, Emanuel ;
Schroeder, Simon ;
Richter, Anja ;
Niemeyer, Daniela ;
Hoffmann, Karen ;
Meyer, Thomas F. ;
Heppner, Frank L. ;
Corman, Victor M. ;
Landthaler, Markus ;
Hocke, Andreas C. ;
Morkel, Markus ;
Osterrieder, Nikolaus ;
Conrad, Christian ;
Eils, Roland ;
Radbruch, Helena ;
Giavalisco, Patrick ;
Drosten, Christian ;
Mueller, Marcel A. .
NATURE COMMUNICATIONS, 2021, 12 (01)
[37]   Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 [J].
Geleris, Joshua ;
Sun, Yifei ;
Platt, Jonathan ;
Zucker, Jason ;
Baldwin, Matthew ;
Hripcsak, George ;
Labella, Angelena ;
Manson, Daniel K. ;
Kubin, Christine ;
Barr, R. Graham ;
Sobieszczyk, Magdalena E. ;
Schluger, Neil W. .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (25) :2411-2418
[38]   Undescribed polyether ionophores from Streptomyces cacaoi and their antibacterial and antiproliferative activities [J].
Gezer, Emre ;
Uner, Goklem ;
Kucuksolak, Melis ;
Kurt, Mustafa Unver ;
Dogan, Gamze ;
Kirmizibayrak, Petek Ballar ;
Bedir, Erdal .
PHYTOCHEMISTRY, 2022, 195
[39]  
Goel Nikky, 2021, Med Drug Discov, V10, P100089, DOI 10.1016/j.medidd.2021.100089
[40]   DISSECTION OF THE GOLGI-COMPLEX .1. MONENSIN INHIBITS THE TRANSPORT OF VIRAL MEMBRANE-PROTEINS FROM MEDIAL TO TRANS GOLGI CISTERNAE IN BABY HAMSTER-KIDNEY CELLS INFECTED WITH SEMLIKI FOREST VIRUS [J].
GRIFFITHS, G ;
QUINN, P ;
WARREN, G .
JOURNAL OF CELL BIOLOGY, 1983, 96 (03) :835-850