Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19
Abstract
:1. Introduction
2. Inflammation Caused by SARS-CoV
3. Anti-Inflammatory Activity of Fenretinide
4. Antiviral Activity of Fenretinide
5. Tolerability of Fenretinide
6. Pulmonary Delivery of Fenretinide in COVID-19
7. Drugs Currently Used in COVID-19
7.1. Antiviral Drugs
7.2. Immunomodulating Drugs Enhancing the Innate Immune System
7.3. Immunomodulating Drugs Attenuating the Inflammatory Response
8. Possible Fenretinide Combinations with Drugs Currently Used in COVID-19
9. Conclusions
Conflicts of Interest
References
- Ren, L.-L.; Wang, Y.-M.; Wu, Z.-Q.; Xiang, Z.-C.; Guo, L.; Xu, T.; Jiang, Y.-Z.; Xiong, Y.; Li, Y.-J.; Li, X.-W.; et al. Identification of a novel coronavirus causing severe pneumonia in human. Chin. Med. J. 2020, 133, 1015–1024. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Y.; Zhao, Z.; Wang, Y.; Zhou, Y.; Ma, Y.; Zuo, W. Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. BioRxiv 2020. preprint. [Google Scholar] [CrossRef]
- Zhou, P.; Yang, X.-L.; Wang, X.-G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.-R.; Zhu, Y.; Li, B.; Huang, C.-L.; et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 579, 270–273. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fu, Y.; Cheng, Y.; Wu, Y. Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools [published online ahead of print, 2020 Mar 3]. Virol Sin. 2020. [Google Scholar] [CrossRef] [Green Version]
- Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef] [Green Version]
- Mody, N.; McIlroy, G.D. The mechanisms of Fenretinide-mediated anti-cancer activity and prevention of obesity and type-2 diabetes. Biochem. Pharmacol. 2014, 91, 277–286. [Google Scholar] [CrossRef] [Green Version]
- Cooper, J.P.; Reynolds, C.P.; Cho, H.; Kang, M.H. Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives. Exp. Boil. Med. 2017, 242, 1178–1184. [Google Scholar] [CrossRef] [Green Version]
- Garaventa, A.; Luksch, R.; Piccolo, M.S.L.; Cavadini, E.; Montaldo, P.G.; Pizzitola, M.R.; Boni, L.; Ponzoni, M.; DeCensi, A.; De Bernardi, B.; et al. Phase I trial and pharmacokinetics of fenretinide in children with neuroblastoma. Clin. Cancer Res. 2003, 9, 2032–2039. [Google Scholar]
- Maurer, B.J.; Kang, M.H.; Villablanca, J.G.; Janeba, J.; Groshen, S.; Matthay, K.K.; Sondel, P.M.; Maris, J.M.; Jackson, H.A.; Goodarzian, F.; et al. Phase I trial of fenretinide delivered orally in a novel organized lipid complex in patients with relapsed/refractory neuroblastoma: A report from the New Approaches to Neuroblastoma Therapy (NANT) consortium. Pediatr. Blood Cancer 2013, 60, 1801–1808. [Google Scholar] [CrossRef] [Green Version]
- Moore, M.M.; Stockler, M.R.; Lim, R.; Mok, T.S.; Millward, M.; Boyer, M. A phase II study of fenretinide in patients with hormone refractory prostate cancer: A trial of the Cancer Therapeutics Research Group. Cancer Chemother. Pharmacol. 2010, 66, 845–850. [Google Scholar] [CrossRef]
- Schneider, B.J.; Worden, F.P.; Gadgeel, S.; Parchment, R.E.; Hodges, C.M.; Zwiebel, J.; Dunn, R.L.; Wozniak, A.J.; Kraut, M.J.; Kalemkerian, G.P. Phase II trial of fenretinide (NSC 374551) in patients with recurrent small cell lung cancer. Investig. New Drugs 2009, 27, 571–578. [Google Scholar] [CrossRef] [PubMed]
- Veronesi, U.; Mariani, L.; DeCensi, A.; Formelli, F.; Camerini, T.; Miceli, R.; Di Mauro, M.G.; Costa, A.; Marubini, E.; Sporn, M.B.; et al. Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Ann. Oncol. 2006, 17, 1065–1071. [Google Scholar] [CrossRef] [PubMed]
- Villablanca, J.; London, W.B.; Naranjo, A.; McGrady, P.; Ames, M.M.; Reid, J.M.; McGovern, R.M.; Buhrow, S.A.; Jackson, H.; Stranzinger, E.; et al. Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: A report from the Children’s Oncology Group. Clin. Cancer Res. 2011, 17, 6858–6866. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Reynolds, C.P.; Frgala, T.; Tsao-Wei, D.D.; Groshen, S.; Morgan, R.; McNamara, M.; Scudder, S.; Zwiebel, J.A.; Lenz, H.J.; Garcia, A.A. High plasma levels of fenretinide (4-HPR) were associated with improved outcome in a phase II study of recurrent ovarian cancer: A study by the California Cancer Consortium. J. Clin. Oncol. 2007, 25, 5555. [Google Scholar] [CrossRef]
- Puduvalli, V.K.; Yung, W.A.; Hess, K.R.; Kuhn, J.G.; Groves, M.D.; Levin, V.A.; Zwiebel, J.; Chang, S.M.; Cloughesy, T.F.; Junck, L.; et al. Phase II Study of Fenretinide (NSC 374551) in Adults With Recurrent Malignant Gliomas: A North American Brain Tumor Consortium Study. J. Clin. Oncol. 2004, 22, 4282–4289. [Google Scholar] [CrossRef] [PubMed]
- Vaishampayan, U.; Heilbrun, L.K.; Parchment, R.E.; Jain, V.; Zwiebel, J.; Boinpally, R.R.; Lorusso, P.; Hussain, M. Phase II trial of fenretinide in advanced renal carcinoma. Investig. New Drugs 2005, 23, 179–185. [Google Scholar] [CrossRef] [Green Version]
- Villablanca, J.; Krailo, M.D.; Ames, M.M.; Reid, J.M.; Reaman, G.H.; Reynolds, C.P. Phase I Trial of Oral Fenretinide in Children With High-Risk Solid Tumors: A Report From the Children’s Oncology Group (CCG 09709). J. Clin. Oncol. 2006, 24, 3423–3430. [Google Scholar] [CrossRef] [PubMed]
- Jasti, B.R.; LoRusso, P.M.; Parchment, R.E.; Wozniak, A.J.; Flaherty, L.E.; Shields, A.F. Phase I clinical trial of fenretinide (NSC374551) in advanced solid tumors. Proc. Am. Soc. Clin. Oncol. 2001, 20, 122a. [Google Scholar]
- Rogers, M.C.; Williams, J.V. Quis Custodiet Ipsos Custodes? Regulation of cell-mediated immune responses following viral lung infections. Annu. Rev. Virol. 2018, 5, 363–383. [Google Scholar] [CrossRef]
- Yang, C.-Y.; Chen, C.-S.; Yiang, G.-T.; Cheng, Y.-L.; Yong, S.-B.; Wu, M.-Y.; Yiang, G.-T. New Insights into the Immune Molecular Regulation of the Pathogenesis of Acute Respiratory Distress Syndrome. Int. J. Mol. Sci. 2018, 19, 588. [Google Scholar] [CrossRef] [Green Version]
- Lachance, C.; Wojewodka, G.; Skinner, T.A.A.; Guilbault, C.; De Sanctis, J.; Radzioch, D. Fenretinide Corrects the Imbalance between Omega-6 to Omega-3 Polyunsaturated Fatty Acids and Inhibits Macrophage Inflammatory Mediators via the ERK Pathway. PLoS ONE 2013, 8, e74875. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guilbault, C.; Wojewodka, G.; Saeed, S.; Hajduch, M.; Matouk, E.; De Sanctis, J.; Radzioch, D. Cystic Fibrosis Fatty Acid Imbalance Is Linked to Ceramide Deficiency and Corrected by Fenretinide. Am. J. Respir. Cell Mol. Boil. 2009, 41, 100–106. [Google Scholar] [CrossRef] [PubMed]
- Saeed, Z.; Guilbault, C.; De Sanctis, J.; Henri, J.; Marion, D.; St-Arnaud, R.; Radzioch, D. Fenretinide prevents the development of osteoporosis in Cftr-KO mice. J. Cyst. Fibros. 2008, 7, 222–230. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- López-Vales, R.; Redensek, A.; Skinner, T.A.A.; Rathore, K.I.; Ghasemlou, N.; Wojewodka, G.; De Sanctis, J.; Radzioch, D.; David, S. Fenretinide Promotes Functional Recovery and Tissue Protection after Spinal Cord Contusion Injury in Mice. J. Neurosci. 2010, 30, 3220–3226. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kanagaratham, C.; Kalivodová, A.; Najdekr, L.; Friedecký, D.; Adam, T.; Hajduch, M.; De Sanctis, J.; Radzioch, D. Fenretinide Prevents Inflammation and Airway Hyperresponsiveness in a Mouse Model of Allergic Asthma. Am. J. Respir. Cell Mol. Boil. 2014, 51, 783–792. [Google Scholar] [CrossRef]
- Li, T.; Zheng, L.-N.; Han, X.-H. Fenretinide attenuates lipopolysaccharide (LPS)-induced blood-brain barrier (BBB) and depressive-like behavior in mice by targeting Nrf-2 signaling. Biomed. Pharmacother. 2020, 125, 109680. [Google Scholar] [CrossRef]
- Yu, H.; Valerio, M.; Bielawski, J. Fenretinide inhibited de novo ceramide synthesis and proinflammatory cytokines induced by Aggregatibacter actinomycetemcomitans. J. Lipid Res. 2012, 54, 189–201. [Google Scholar] [CrossRef] [Green Version]
- Zhang, H.; Mi, J.-Q.; Fang, H.; Wang, Z.; Wang, C.; Wu, L.; Zhang, B.; Minden, M.; Yang, W.-T.; Wang, H.; et al. Preferential eradication of acute myelogenous leukemia stem cells by fenretinide. Proc. Natl. Acad. Sci. USA 2013, 110, 5606–5611. [Google Scholar] [CrossRef] [Green Version]
- Makena, M.R.; Koneru, B.; Nguyen, T.H.; Kang, M.H.; Reynolds, C.P. Reactive oxygen species-mediated synergism of fenretinide and romidepsin in preclinical models of T-cell lymphoid malignancies. Mol. Cancer Ther. 2017, 16, 649–661. [Google Scholar] [CrossRef] [Green Version]
- Asumendi, A.; Morales, M.C.; Alvarez, A.; Aréchaga, J.; Pérez-Yarza, G. Implication of mitochondria-derived ROS and cardiolipin peroxidation in N-(4-hydroxyphenyl)retinamide-induced apoptosis. Br. J. Cancer 2002, 86, 1951–1956. [Google Scholar] [CrossRef] [Green Version]
- Yan, D.; Weisshaar, M.; Lamb, K.; Chung, H.K.; Lin, M.Z.; Plemper, R.K. Replication-Competent Influenza Virus and Respiratory Syncytial Virus Luciferase Reporter Strains Engineered for Co-Infections Identify Anti-viral Compounds in Combination Screens. Biochemistry 2015, 54, 5589–5604. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fraser, J.E.; Watanabe, S.; Wang, C.; Chan, W.K.; Maher, B.; Lopez Denman, A.; Hick, C.; Wagstaff, K.M.; Mackenzie, J.M.; Sexton, P.M.; et al. A nuclear transport inhibitor that modulates the unfolded protein response and provides in vivo protection against lethal dengue virus infection. J. Infect. Dis. 2014, 210, 1780–1791. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fraser, J.; Wang, C.; Chan, K.; Vasudevan, S.; Jans, D.A. Novel dengue virus inhibitor 4-HPR activates ATF4 independent of protein kinase R–like Endoplasmic Reticulum Kinase and elevates levels of eIF2α phosphorylation in virus infected cells. Antivir. Res. 2016, 130, 1–6. [Google Scholar] [CrossRef] [PubMed]
- Carocci, M.; Hinshaw, S.M.; Rodgers, M.A.; Villareal, V.A.; Burri, D.J.; Pilankatta, R.; Maharaj, N.P.; Gack, M.U.; Stavale, E.J.; Warfield, K.L.; et al. The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication. Antimicrob. Agents Chemother. 2014, 59, 85–95. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pitts, J.D.; Li, P.C.; de Wispelaere, M.; Yang, P.L. Anti-viral activity of N-(4-hydroxyphenyl) retinamide (4-HPR) against Zika virus. Antivir. Res. 2017, 147, 124–130. [Google Scholar] [CrossRef]
- Wang, C.; Yang, S.N.; Smith, K.; Forwood, J.K.; Jans, D.A. Nuclear import inhibitor N -(4-hydroxyphenyl) retinamide targets Zika virus (ZIKV) nonstructural protein 5 to inhibit ZIKV infection. Biochem. Biophys. Res. Commun. 2017, 493, 1555–1559. [Google Scholar] [CrossRef]
- Best, S.M. The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon Signaling. J. Virol. 2016, 91, e01970-16. [Google Scholar] [CrossRef] [Green Version]
- Channappanavar, R.; Fehr, A.R.; Zheng, J.; Wohlford-Lenane, C.; Abrahante, J.E.; Mack, M.; Sompallae, R.; McCray, P.B.; Meyerholz, D.K.; Perlman, S. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J. Clin. Investig. 2019, 130, 3625–3639. [Google Scholar] [CrossRef]
- Kindler, E.; Thiel, V. To sense or not to sense viral RNA—essentials of coronavirus innate immune evasion. Curr. Opin. Microbiol. 2014, 20, 69–75. [Google Scholar] [CrossRef]
- Zhao, L.; Jha, B.K.; Wu, A.; Elliott, R.; Ziebuhr, J.; Gorbalenya, A.E.; Silverman, R.H.; Weiss, S.R. Antagonism of the Interferon-Induced OAS-RNase L Pathway by Murine Coronavirus ns2 Protein Is Required for Virus Replication and Liver Pathology. Cell Host Microbe 2012, 11, 607–616. [Google Scholar] [CrossRef] [Green Version]
- Kindler, E.; Thiel, V. SARS-CoV and IFN: Too Little, Too Late. Cell Host Microbe 2016, 19, 139–141. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Finnegan, C.M.; Blumenthal, R. Fenretinide inhibits HIV infection by promoting viral endocytosis. Antivir. Res. 2006, 69, 116–123. [Google Scholar] [CrossRef] [PubMed]
- Finnegan, C.M.; Rawat, S.S.; Puri, A.; Wang, J.M.; Ruscetti, F.W.; Blumenthal, R. Ceramide, a target for antiretroviral therapy. Proc. Natl. Acad. Sci. USA 2004, 101, 15452–15457. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, N.; Shen, H.-M. Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19. Int. J. Boil. Sci. 2020, 16, 1724–1731. [Google Scholar] [CrossRef] [PubMed]
- Gassen, N.C.; Niemeyer, D.; Muth, D.; Corman, V.; Martinelli, S.; Gassen, A.; Hafner, K.; Papies, J.; Mösbauer, K.; Zellner, A.; et al. SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. Nat. Commun. 2019, 10, 1–16. [Google Scholar] [CrossRef] [PubMed]
- Dong, X.; Levine, B. Autophagy and viruses: Adversaries or allies? J. Innate Immun. 2013, 5, 480–493. [Google Scholar] [CrossRef] [PubMed]
- Fazi, B.; Bursch, W.; Fimia, G.M.; Nardacci, R.; Piacentini, M.; Di Sano, F.; Piredda, L. Fenretinide induces autophagic cell death in caspase-defective breast cancer cells. Autophagy 2008, 4, 435–441. [Google Scholar] [CrossRef] [Green Version]
- Messner, M.C.; Cabot, M.C. Cytotoxic responses to N-(4-hydroxyphenyl)retinamide in human pancreatic cancer cells. Cancer Chemother. Pharmacol. 2010, 68, 477–487. [Google Scholar] [CrossRef]
- Gagliostro, V.; Casas, J.; Caretti, A.; Abad, J.L.; Tagliavacca, L.; Ghidoni, R.; Fabrias, G.; Signorelli, P. Dihydroceramide delays cell cycle G1/S transition via activation of ER stress and induction of autophagy. Int. J. Biochem. Cell Biol. 2012, 44, 2135–2143. [Google Scholar] [CrossRef]
- Kindrachuk, J.; Ork, B.; Hart, B.J.; Mazur, S.; Holbrook, M.R.; Frieman, M.B.; Traynor, D.; Johnson, R.F.; Dyall, J.; Kuhn, J.H.; et al. Anti-viral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob Agents Chemother. 2015, 59, 1088–1099. [Google Scholar] [CrossRef] [Green Version]
- Kim, Y.C.; Guan, K.-L. mTOR: A pharmacologic target for autophagy regulation. J. Clin. Investig. 2015, 125, 25–32. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Orienti, I.; Francescangeli, F.; De Angelis, M.L.; Fecchi, K.; Bongiorno-Borbone, L.; Signore, M.; Peschiaroli, A.; Boe, A.; Bruselles, A.; Costantino, A.; et al. A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors. Cell Death Dis. 2019, 10, 529. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Benelli, R.; Monteghirfo, S.; Venè, R.; Tosetti, F.; Ferrari, N. The chemopreventive retinoid 4HPR impairs prostate cancer cell migration and invasion by interfering with FAK/AKT/GSK3beta pathway and beta-catenin stability. Mol. Cancer 2010, 9, 142. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Formelli, F.; Cavadini, E.; Luksch, R.; Garaventa, A.; Villani, M.G.; Appierto, V.; Persiani, S. Pharmacokinetics of oral fenretinide in neuroblastoma patients: Indications for optimal dose and dosing schedule also with respect to the active metabolite 4-oxo-fenretinide. Cancer Chemother. Pharmacol. 2008, 62, 655–665. [Google Scholar] [CrossRef] [PubMed]
- Cheung, E.; Pinski, J.; Dorff, T.; Groshen, S.; Quinn, D.I.; Reynolds, C.P.; Maurer, B.J.; Lara, P.N.; Tsao-Wei, D.D.; Twardowski, P.; et al. Oral Fenretinide in Biochemically Recurrent Prostate Cancer: A California Cancer Consortium Phase II Trial. Clin. Genitourin. Cancer 2009, 7, 43–50. [Google Scholar] [CrossRef] [PubMed]
- Cowan, A.J.; Stevenson, P.A.; Gooley, T.A.; Frayo, S.L.; Oliveira, G.R.; Smith, S.D.; Green, D.J.; Roden, J.E.; Pagel, J.M.; Wood, B.L.; et al. Results of a phase I-II study of fenretinide and rituximab for patients with indolent B-cell lymphoma and mantle cell lymphoma. Br. J. Haematol. 2017, 176, 583–590. [Google Scholar] [CrossRef] [Green Version]
- Garewal, H.S.; List, A.F.; Meyskens, F.; Buzaid, A.; Greenberg, B.; Katakkar, S. Phase II trial of fenretinide [N-(4-Hydroxyphenyl) retinamide] in myelodysplasia: Possible retinoid-induced disease acceleration. Leuk. Res. 1989, 13, 339–343. [Google Scholar] [CrossRef] [Green Version]
- Mohrbacher, A.M.; Yang, A.S.; Groshen, S.; Kummar, S.; Gutierrez, M.E.; Kang, M.H.; Tsao-Wei, D.; Reynolds, C.P.; Newman, E.M.; Maurer, B.J. Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or Refractory Hematologic Malignancies: A California Cancer Consortium Trial. Clin. Cancer Res. 2017, 23, 4550–4555. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Busnelli, M.; Manzini, S.; Bonacina, F.; Soldati, S.; Barbieri, S.S.; Amadio, P.; Sandrini, L.; Arnaboldi, F.; Donetti, E.; Laaksonen, R.; et al. Fenretinide treatment accelerates atherosclerosis development in apoE-deficient mice in spite of beneficial metabolic effects. Br. J. Pharmacol. 2019, 177, 328–345. [Google Scholar] [CrossRef] [Green Version]
- Camerini, T.; Mariani, L.; De Palo, G.; Marubini, E.; Di Mauro, M.G.; DeCensi, A.; Costa, A.; Veronesi, U. Safety of the Synthetic Retinoid Fenretinide: Long-Term Results from a Controlled Clinical Trial for the Prevention of Contralateral Breast Cancer. J. Clin. Oncol. 2001, 19, 1664–1670. [Google Scholar] [CrossRef]
- Videira, M.A.; Llop, J.; Sousa, C.; Kreutzer, B.; Cossío, U.; Forbes, B.; Vieira, I.; Gil, N.; Silva-Lima, B. Pulmonary Administration: Strengthening the Value of Therapeutic Proximity. Front. Med. (Lausanne) 2020, 7, 50. [Google Scholar] [CrossRef] [PubMed]
- Gupta, V.K.; Bahia, J.S.; Maheshwari, A.; Arora, S.; Gupta, V.; Nohria, S. To study the attitudes, beliefs and perceptions regarding the use of inhalers among patients of obstructive pulmonary diseases and in the general population in Punjab. J. Clin. Diagn. Res. 2011, 5, 434–439. [Google Scholar]
- Sanchis, J.; Pedersen, S.; on behalf of the ADMIT Team. Systematic review of errors in inhaler use: Has patient technique improved over time? Chest 2016, 150, 394–406. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Newman, S.P. Drug delivery to the lungs: Challenges and opportunities. Ther. Deliv. 2017, 8, 647–661. [Google Scholar] [CrossRef] [PubMed]
- Van Heeke, G.; Allosery, K.; De Brabandere, V.; De Smedt, T.; Detalle, L.; De Fougerolles, A. Nanobodies® † Nanobody is a registered trademark of Ablynx NV. As inhaled biotherapeutics for lung diseases. Pharmacol. Ther. 2017, 169, 47–56. [Google Scholar] [CrossRef]
- Orienti, I.; Nguyen, F.; Guan, P.; Kolla, V.; Calonghi, N.; Farruggia, G.; Chorny, M.; Brodeur, G.M. A Novel Nanomicellar Combination of Fenretinide and Lenalidomide Shows Marked Antitumor Activity in a Neuroblastoma Xenograft Model. Drug Des. Dev. Ther. 2019, 13, 4305–4319. [Google Scholar] [CrossRef] [Green Version]
- Sheahan, T.P.; Sims, A.C.; Graham, R.L.; Menachery, V.D.; Gralinski, L.E.; Case, J.B.; Leist, S.R.; Pyrc, K.; Feng, J.Y.; Trantcheva, I.; et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med. 2017, 9, 3653. [Google Scholar] [CrossRef] [Green Version]
- Agostini, M.L.; Andres, E.L.; Sims, A.C.; Graham, R.L.; Sheahan, T.P.; Lu, X.; Smith, E.C.; Case, J.B.; Feng, J.Y.; Jordan, R.; et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio 2018, 9, e00221-18. [Google Scholar] [CrossRef] [Green Version]
- Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020, 30, 269–271. [Google Scholar] [CrossRef]
- Wagsta, K.M.; Sivakumaran, H.; Heaton, S.M.; Harrich, D.; Jans, D.A. Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem. J. 2012, 443, 851–856. [Google Scholar] [CrossRef] [Green Version]
- Caly, L.; Druce, J.D.; Catton, M.G.; Jans, D.A.; Wagstaff, K.M. The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antivir. Res. 2020, 104787. [Google Scholar] [CrossRef] [PubMed]
- Chan, J.F.W.; Yao, Y.; Yeung, M.L.; Deng, W.; Bao, L.; Jia, L.; Li, F.; Xiao, C.; Gao, H.; Yu, P.; et al. Treatment with lopinavir / ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J. Infect. Dis. 2015, 212, 1904e13. [Google Scholar] [CrossRef] [PubMed]
- Sheahan, T.P.; Sims, A.C.; Leist, S.R.; Schäfer, A.; Won, J.; Brown, A.J.; Montgomery, S.A.; Hogg, A.; Babusis, D.; Clarke, M.O.; et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun. 2020, 11, 222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cao, B.; Wang, Y.; Wen, D.; Liu, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. N. Engl. J. Med. 2020, 382, 1787–1799. [Google Scholar] [CrossRef]
- Savarino, A.; Boelaert, J.R.; Cassone, A.; Majori, G.; Cauda, R. Effects of chloroquine on viral infections: An old drug against today’s diseases. Lancet Infect. Dis. 2003, 3, 722–727. [Google Scholar] [CrossRef]
- Vincent, M.J.; Bergeron, É.; Benjannet, S.; Erickson, B.R.; E Rollin, P.; Ksiazek, T.G.; Seidah, N.G.; Nichol, S.T. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J. 2005, 2, 69. [Google Scholar] [CrossRef] [Green Version]
- Lan, L.; Xu, D.; Ye, G.; Xia, C.; Wang, S.; Li, Y.-R.; Xu, H. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA 2020, 323, 1502–1503. [Google Scholar] [CrossRef] [Green Version]
- Chen, J.; Lau, Y.F.; Lamirande, E.W.; Paddock, C.D.; Bartlett, J.H.; Zaki, S.R.; Subbarao, K. Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+ T Cells Are Important in Control of SARS-CoV Infection. J. Virol. 2009, 84, 1289–1301. [Google Scholar] [CrossRef] [Green Version]
- Cinatl, J.; Morgenstern, B.; Bauer, G.; Chandra, P.; Rabenau, H.; Doerr, H.W. Treatment of SARS with human interferons. Lancet 2003, 362, 293–294. [Google Scholar] [CrossRef]
- Rose-John, S. IL-6 Trans-Signaling via the Soluble IL-6 Receptor: Importance for the Pro-Inflammatory Activities of IL-6. Int. J. Boil. Sci. 2012, 8, 1237–1247. [Google Scholar] [CrossRef]
- Voiriot, G.; Razazi, K.; Amsellem, V.; Van Nhieu, J.T.; Abid, S.; Adnot, S.; Dessap, A.M.; Maitre, B. Interleukin-6 displays lung anti-inflammatory properties and exerts protective hemodynamic effects in a double-hit murine acute lung injury. Respir. Res. 2017, 18, 64. [Google Scholar] [CrossRef] [PubMed]
- Rose-John, S.; Waetzig, G.H.; Scheller, J.; Grotzinger, J.; Seegert, D. The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert. Opin. Ther. Targets 2007, 11, 613–624. [Google Scholar] [CrossRef] [PubMed]
- Vargesson, N. Thalidomide-induced teratogenesis: History and mechanisms. Birth Defects Res. Part C: Embryo Today: Rev. 2015, 105, 140–156. [Google Scholar] [CrossRef] [Green Version]
- Zhu, H.; Shi, X.; Ju, D.; Huang, H.; Wei, W.; Dong, X. Anti-Inflammatory Effect of Thalidomide on H1N1 Influenza Virus-Induced Pulmonary Injury in Mice. Inflammation 2014, 37, 2091–2098. [Google Scholar] [CrossRef] [PubMed]
- Tu, Y.-F.; Chien, C.-S.; Yarmishyn, A.; Lin, Y.-Y.; Luo, Y.-H.; Lin, Y.-T.; Lai, W.-Y.; Yang, D.-M.; Chou, S.-J.; Yang, Y.-P.; et al. A Review of SARS-CoV-2 and the Ongoing Clinical Trials. Int. J. Mol. Sci. 2020, 21, 2657. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Borhani, K.; Bamdad, T.; Hashempour, T. Lenalidomide acts as an adjuvant for HCV DNA vaccine. Int. Immunopharmacol. 2017, 48, 231–240. [Google Scholar] [CrossRef]
- Yamamoto, K.; Kitawaki, T.; Sugimoto, N.; Fujita, H.; Kawase, Y.; Takaori-Kondo, A.; Kadowaki, N. Anti-inflammatory modulation of human myeloid-derived dendritic cell subsets by lenalidomide. Immunol. Lett. 2019, 211, 41–48. [Google Scholar] [CrossRef]
- Kotla, V.; Goel, S.; Nischal, S.; Heuck, C.; Vivek, K.; Das, B.C.; Verma, A. Mechanism of action of lenalidomide in hematological malignancies. J. Hematol. Oncol. 2009, 2, 36. [Google Scholar] [CrossRef] [Green Version]
- Buesche, G.; Dieck, S.; Giagounidis, A.; Bock, O.; Wilkens, L.; Schlegelberger, B.; Knight, R.; Bennett, J.; Aul, C.; Kreipe, H.H. Antiangiogenic in vivo effect of lenalidomide (CC-5013) in myelodysplastic syndrome with del (5q) chromosome abnormality and its relation to the course of disease [abstract]. Blood 2005, 106, 372. [Google Scholar] [CrossRef]
- Dredge, K.; Horsfall, R.; Robinson, S.P.; Zhang, L.-H.; Lu, L.; Tang, Y.; Shirley, M.A.; Muller, G.; Schäfer, P.; Stirling, D.; et al. Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc. Res. 2005, 69, 56–63. [Google Scholar] [CrossRef]
- Lu, L.; Payvandi, F.; Wu, L.; Zhang, L.-H.; Hariri, R.J.; Man, H.-W.; Chen, R.S.; Muller, G.W.; Hughes, C.C.; Stirling, D.I.; et al. The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Microvasc. Res. 2009, 77, 78–86. [Google Scholar] [CrossRef] [PubMed]
- Stockman, L.J.; Bellamy, R.; Garner, P. SARS: Systematic Review of Treatment Effects. PLoS Med. 2006, 3, e343. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Arabi, Y.M.; Mandourah, Y.; Al-Hameed, F.; Sindi, A.A.; Almekhlafi, G.A.; Hussein, M.A.; Jose, J.; Pinto, R.; Al-Omari, A.; Kharaba, A.; et al. Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. Am. J. Respir. Crit. Care Med. 2018, 197, 757–767. [Google Scholar] [CrossRef] [PubMed]
- Venkatesh, B.; Finfer, S.; Cohen, J.; Rajbhandari, D.; Arabi, Y.; Bellomo, R.; Billot, L.; Correa, M.; Glass, P.; Harward, M.; et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N. Engl. J. Med. 2018, 378, 797–808. [Google Scholar] [CrossRef]
- Zhao, Z.; Matsuura, T.; Popoff, K.; Ross, A.C. Effects of N-(4-hydroxyphenyl)-retinamide on the number and cytotoxicity of natural killer cells in vitamin-A-sufficient and -deficient rats. Nat. Immun. 1994, 13, 280–288. [Google Scholar]
- Villa, M.L.; Ferrario, E.; Trabattoni, D.; Formelli, F.; De Palo, G.; Magni, A.; Veronesi, U.; Clerici, E. Retinoids, breast cancer and NK cells. Br. J. Cancer 1993, 68, 845–850. [Google Scholar] [CrossRef] [Green Version]
- Sogno, I.; Venè, R.; Sapienza, C.; Ferrari, N.; Tosetti, F.; Albini, A. Anti-angiogenic properties of Chemopreventive Drugs: Fenretinide as a Prototype. Adv. Struct. Saf. Stud. 2008, 181, 71–76. [Google Scholar]
- Ribatti, D.; Raffaghello, L.; Marimpietri, D.; Cosimo, E.; Montaldo, P.G.; Nico, B.; Vacca, A.; Ponzoni, M. Fenretinide as an anti-angiogenic agent in neuroblastoma. Cancer Lett. 2003, 197, 181–184. [Google Scholar] [CrossRef]
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Orienti, I.; Gentilomi, G.A.; Farruggia, G. Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19. Int. J. Mol. Sci. 2020, 21, 3812. https://doi.org/10.3390/ijms21113812
Orienti I, Gentilomi GA, Farruggia G. Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19. International Journal of Molecular Sciences. 2020; 21(11):3812. https://doi.org/10.3390/ijms21113812
Chicago/Turabian StyleOrienti, Isabella, Giovanna Angela Gentilomi, and Giovanna Farruggia. 2020. "Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19" International Journal of Molecular Sciences 21, no. 11: 3812. https://doi.org/10.3390/ijms21113812