Endocytic Pathway of Feline Coronavirus for Cell Entry: Differences in Serotype-Dependent Viral Entry Pathway

Takano, Tomomi; Wakayama, Yumeho; Doki, Tomoyoshi

doi:10.3390/pathogens8040300

Cited by 17 publications

(22 citation statements)

References 51 publications

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“…The oxysterol 25-hydroxycholesterol is a metabolite of cholesterol that is produced and secreted by macrophages and has multiple effects on lipid metabolism, especially lipid biosynthesis and immunity [ 63 ]. 25-hydroxycholetserol has been shown to inhibit feline coronavirus, porcine epidemic diarrhea virus, and porcine transmissible gastroenteritis virus possibly through induction of intracellular cholesterol accumulation [ 64 , 65 ]. Moreover, 25-hydroxycholesterol is active against various emerging RNA viruses, including Ebola virus, Nipah virus, Rift Valley fever virus, and Zika virus, and DNA and RNA viruses that cause chronic infections, such as human immunodeficiency virus, herpes simplex virus, and varicella zoster virus [ 18 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)

Yuan

Chan

Chik

et al. 2020

Viruses

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The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.

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Section: Discussionmentioning

confidence: 99%

Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)

Yuan

Chan

Chik

et al. 2020

Viruses

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“…Moreover, available NPC1 inhibitors U1866A and imipramine inhibited several enveloped viruses including MERS-CoV and SARS-CoV ( Wrensch et al, 2014 ), Ebola ( Herbert et al, 2015 ; Lu et al, 2015 ), HIV-1 ( Tang et al, 2009 ), HCV ( Elgner et al, 2016 ), influenza A ( Eckert et al, 2014 ), and chikungunya ( Wichit et al, 2017 ) by de-acidifying endolysosomes and increasing lipid accumulation ( Lange et al, 2012 ) ( Figure 2 ). Also, the anti-fungal drugs itraconazole and posaconazole are not only inhibitors of NPC but also have antiviral activity ( Strating et al, 2015 ; Trinh et al, 2017 ; Meutiawati et al, 2018 ; Rhoden et al, 2018 ; Schloer et al, 2019 ; Takano et al, 2019a ; Takano et al, 2019b ). In addition, cepharanthine, an inhibitor of TPC2 and NPC1, has antiviral activity ( Figure 2 ) ( Zhang et al, 2005 ; Matsuda et al, 2014 ; Lyu et al, 2017 ; Bailly, 2019 ; Kim et al, 2019 ; Fan et al, 2020 ; Rogosnitzky et al, 2020 ).…”

Section: Effects Of Endolysosome Ph On Coronavirus Infectionmentioning

confidence: 99%

Role of Endolysosomes in Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Coronavirus Disease 2019 Pathogenesis: Implications for Potential Treatments

2020

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an enveloped, single-stranded RNA virus. Humans infected with SARS-CoV-2 develop a disease known as coronavirus disease 2019 (COVID-19) with symptoms and consequences including acute respiratory distress syndrome (ARDS), cardiovascular disorders, and death. SARS-CoV-2 appears to infect cells by first binding viral spike proteins with host protein angiotensin-converting enzyme 2 (ACE2) receptors; the virus is endocytosed following priming by transmembrane protease serine 2 (TMPRSS2). The process of virus entry into endosomes and its release from endolysosomes are key features of enveloped viruses. Thus, it is important to focus attention on the role of endolysosomes in SARS-CoV-2 infection. Indeed, coronaviruses are now known to hijack endocytic machinery to enter cells such that they can deliver their genome at replication sites without initiating host detection and immunological responses. Hence, endolysosomes might be good targets for developing therapeutic strategies against coronaviruses. Here, we focus attention on the involvement of endolysosomes in SARS-CoV-2 infection and COVID-19 pathogenesis. Further, we explore endolysosome-based therapeutic strategies to restrict SARS-CoV-2 infection and COVID-19 pathogenesis.

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“…We consider these drugs to be a treatment option until antiviral drugs such as GC-376 and GS-441524 become available. In addition, these antiviral drugs exert therapeutic effects on FIP by mechanisms different from those of ADA and ICZ [16,18,21,23]. In the future, the evaluation of the therapeutic effects of their concomitant use may aid in the development of more-effective treatments for FIP.…”

Section: Discussionmentioning

confidence: 99%

“…These drugs have been confirmed to reduce the proliferation of FIPV, but they are not commercially distributed as veterinary drugs. We previously found that itraconazole (ICZ), which is used in veterinary medicine, reduces the proliferation of type I FIPV [21][22][23]. However, the therapeutic effects of ICZ in cats with FIP remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of an anti-human-TNF-alpha antibody and itraconazole on feline infectious peritonitis

et al. 2020

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Feline infectious peritonitis (FIP) is a fatal disease in wild and domestic cat species. Although several drugs are expected to be useful as treatments for FIP, no drugs are available in clinical practice. In this study, we evaluated the therapeutic effect of combined use of adalimumab (an anti-human-TNF-alpha monoclonal antibody, ADA) and itraconazole (ICZ), which are presently available to veterinarians. The neutralizing activity of ADA against fTNF-alpha-induced cytotoxicity was measured in WEHI-164 cells. Ten specific pathogen-free (SPF) cats were inoculated intraperitoneally with type I FIPV KU-2. To the cats that developed FIP, ADA (10 mg/animal) was administered twice between day 0 and day 4 after the start of treatment. ICZ (50 mg/head, SID) was orally administered daily from day 0 after the start of treatment. ADA demonstrated dose-dependent neutralizing activity against rfTNF-alpha. In an animal experiment, 2 of 3 cats showed improvements in FIP clinical symptoms and blood chemistry test results, an increase in the peripheral blood lymphocyte count, and a decrease in the plasma alpha 1-AGP level were observed after the beginning of treatment. One of the cats failed to respond to treatment and was euthanized, although the viral gene level in ascites temporarily decreased after the start of treatment. ADA was found to have neutralizing activity against rfTNF-alpha. The combined use of ADA and ICZ showed a therapeutic effect for experimentally induced FIP. We consider these drugs to be a treatment option until effective anti-FIPV drugs become available.

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Endocytic Pathway of Feline Coronavirus for Cell Entry: Differences in Serotype-Dependent Viral Entry Pathway

Cited by 17 publications

References 51 publications

Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)

Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)

Role of Endolysosomes in Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Coronavirus Disease 2019 Pathogenesis: Implications for Potential Treatments

Therapeutic effect of an anti-human-TNF-alpha antibody and itraconazole on feline infectious peritonitis

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