Influences of cyclosporin A and non-immunosuppressive derivatives on cellular cyclophilins and viral nucleocapsid protein during human coronavirus 229E replication

Publication date: January 2020Source: Antiviral Research, Volume 173Author(s): Yue Ma-Lauer, Yu Zheng, Miroslav Malešević, Brigitte von Brunn, Gunter Fischer, Albrecht von BrunnAbstractThe well-known immunosuppressive drug cyclosporin A inhibits replication of various viruses including coronaviruses by binding to cellular cyclophilins thus inactivating their cis-trans peptidyl-prolyl isomerase function. Viral nucleocapsid proteins are inevitable for genome encapsidation and replication. Here we demonstrate the interaction between the N protein of HCoV-229E and cyclophilin A, not cyclophilin B. Cyclophilin inhibitors abolish this interaction. Upon infection, cyclophilin A stays evenly distributed throughout the cell, whereas cyclophilin B concentrates at ER-bleb-like structures. We further show the inhibitory potential of non-immunosuppressive CsA derivatives Alisporivir, NIM811, compound 3 on HCoV-229E-GFP and -Luciferase replication in human Huh-7.5 hepatoma cells at 18 and 48 h time points post infection with EC50 s at low micromolar ranges. Thus, non-immunosuppressive CsA derivatives effectively inhibit HCoV-229E replication suggesting them as possible candidates for the treatment of HCoV infection. The interruption of interaction between CypA and N protein by CsA and its derivatives suggest a mechanism how CypA inhibitors suppress viral replication.
Source: Antiviral Therapy - Category: Virology Source Type: research

Related Links:

Symptom-based health screening of passengers entering the US on direct or connecting flights from Wuhan, China, will be conducted in San Francisco, New York, and Los Angeles.Medscape Medical News
Source: Medscape Allergy Headlines - Category: Allergy & Immunology Tags: Infectious Diseases News Source Type: news
Publication date: Available online 16 January 2020Source: Cell ReportsAuthor(s): Shaobo Wang, Qiong Zhang, Shashi Kant Tiwari, Gianluigi Lichinchi, Edwin H. Yau, Hui Hui, Wanyu Li, Frank Furnari, Tariq M. RanaSummaryWe perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin αvβ5 as an internalization factor for Zika virus (ZIKV). Expression of αvβ5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibody against integrin αvβ5, but not αvβ3, efficiently inhibits ZIKV infection. ZI...
Source: Cell Reports - Category: Cytology Source Type: research
Publication date: Available online 16 January 2020Source: The Veterinary JournalAuthor(s): P. Pansri, J. Katholm, K.M. Krogh, A.K. Aagaard, L.M.B. Schmidt, E. Kudirkiene, L.E. Larsen, J.E. OlsenAbstractBovine respiratory disease complex is the most common disease requiring the use of antimicrobials in industrial calf production worldwide. Pathogenic bacteria (Mannheimia haemolytica (Mh), Pasteurella multocida (Pm), Histophilus somni (Hs), and Mycoplasma bovis) and a range of viruses (bovine respiratory syncytial virus, bovine coronavirus, bovine parainfluenza virus type 3, bovine viral diarrhea virus and bovine herpesvirus...
Source: The Veterinary Journal - Category: Veterinary Research Source Type: research
Authors: Ogasawara S, Ooka Y, Koroki K, Maruta S, Kanzaki H, Kanayama K, Kobayashi K, Kiyono S, Nakamura M, Kanogawa N, Saito T, Kondo T, Suzuki E, Nakamoto S, Tawada A, Chiba T, Arai M, Kato J, Kato N Abstract In patients with unresectable hepatocellular carcinoma (HCC) without both macrovascular invasion and extrahepatic metastasis, the initial treatment choice recommended is transarterial chemoembolization (TACE). Before sorafenib came into wide use, TACE had been pointlessly carried out repeatedly. It was in the early 2010s that the concept of TACE refractory was advocated. Two retrospective studies from Japan ...
Source: Clinical and molecular hepatology - Category: Gastroenterology Tags: Clin Mol Hepatol Source Type: research
Source: BMJ Comments - Category: General Medicine Source Type: forums
Publication date: Available online 18 October 2019Source: Antiviral ResearchAuthor(s): Yue Ma-Lauer, Yu Zheng, Miroslav Malešević, Brigitte von Brunn, Gunter Fischer, Albrecht von BrunnAbstractThe well-known immunosuppressive drug cyclosporin A inhibits replication of various viruses including coronaviruses by binding to cellular cyclophilins thus inactivating their cis-trans peptidyl-prolyl isomerase function. Viral nucleocapsid proteins are inevitable for genome encapsidation and replication. Here we demonstrate the interaction between the N protein of HCoV-229E and cyclophilin A, not cyclophilin B. Cyclophilin i...
Source: Antiviral Therapy - Category: Virology Source Type: research
unn A Abstract The well-known immunosuppressive drug cyclosporin A inhibits replication of various viruses including coronaviruses by binding to cellular cyclophilins thus inactivating their cis-trans peptidyl-prolyl isomerase function. Viral nucleocapsid proteins are inevitable for genome encapsidation and replication. Here we demonstrate the interaction between the N protein of HCoV-229E and cyclophilin A, not cyclophilin B. Cyclophilin inhibitors abolish this interaction. Upon infection, cyclophilin A stays evenly distributed throughout the cell, whereas cyclophilin B concentrates at ER-bleb-like structures. We...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research
Yíngyún Caì1†, Shuǐqìng Yú1†, Rohit K. Jangra2, Elena N. Postnikova1, Jiro Wada1, Robert B. Tesh3, Sean P. J. Whelan4, Michael Lauck5, Michael R. Wiley6, Courtney L. Finch1, Sheli R. Radoshitzky6, David H. O’Connor5, Gustavo Palacios6, Kartik Chandran2, Charles Y. Chiu7 and Jens H. Kuhn1* 1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, United States 2Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, United States 3Depart...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Life after losing a loved one to vaccines is very painful. With a heavy heart, we share Sebastian Ryan Morley’s story. He was a healthy boy whose life ended after routine vaccinations. Sebastian’s mother and grandmother have worked many years in both the veterinary and human healthcare fields. What they were taught in school led them to believe vaccines were safe, but now they will never vaccinate again. We thank his family for coming forward and sharing very important information the public isn’t usually made aware of. Sebastian’s grandmother, Valerie Murfin, shared: “On December 11, 2002, wh...
Source: vactruth.com - Category: Allergy & Immunology Authors: Tags: Augustina Ursino Human Top Stories adverse reactions dtap Hepatitis B vaccine Sebastian Ryan Morley truth about vaccines Vaccine Death vaccine injury VAERS Valerie Murfin Source Type: blogs
Publication date: Available online 23 July 2015 Source:Cell Reports Author(s): Gisa Gerold, Felix Meissner, Janina Bruening, Kathrin Welsch, Paula M. Perin, Thomas F. Baumert, Florian W. Vondran, Lars Kaderali, Joseph Marcotrigiano, Abdul G. Khan, Matthias Mann, Charles M. Rice, Thomas Pietschmann Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitativ...
Source: Cell Reports - Category: Cytology Source Type: research
More News: Antiviral Therapy | Coronavirus | Hepatocellular Carcinoma | Liver Cancer | Virology