Cyclosporin A Inhibits the Propagation of Influenza Virus by Interfering with a Late Event in the Virus Life Cycle

Hamamoto, Itsuki; Harazaki, Kazuhiro; Inase, Naohiko; Takaku, Hiroshi; Tashiro, Masato; Yamamoto, Norio

doi:10.7883/yoken.66.276

Cited by 21 publications

(18 citation statements)

References 33 publications

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“…The requirement of VSV-NJ for CypA for its replication and the possible association of CypA in other subtypes of VSV-IND and/or VSV-NJ needs detailed studies (Bose et al, 2003). Furthermore, the accurate molecular mechanism of anti-influenza virus activity of CypA and CsA (CypA dependent) needs further clarification (Hamamoto et al, 2013). The mechanism of CypA association in JNK signals to facilitate IFNb production and the critical role in the inhibition of RV protein expression required clearification (He et al, , 2013.…”

Section: Conclusion and Future View Pointmentioning

confidence: 99%

Cyclophilin A: A Key Factor in Virus Replication and Potential Target for Anti-viral Therapy

Dawar

Tu²,

Khattak³

et al. 2017

Current Issues in Molecular Biology

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Cyclophilin A (CypA) is a key member of immunophilins that has peptidyl-prolyl cis/trans isomerase (PPIase) activity. Besides acting as a cellular receptor for immunosuppressive drug cyclosporine A (CsA), CypA is involved in various cellular activities. CypA has an important role in viral infection which either facilitates or inhibits their replication. Inhibition of CypA via inhibitors is useful for overcoming several viral infections, indicating that CypA is an attractive target for anti-viral therapy. Collectively, these facts demonstrate the critical roles of CypA in mediating or inhibiting viral infections, suggesting that CypA can be an attractive cellular target for the development of anti-viral therapy.

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Section: Conclusion and Future View Pointmentioning

confidence: 99%

Cyclophilin A: A Key Factor in Virus Replication and Potential Target for Anti-viral Therapy

Dawar

Tu²,

Khattak³

et al. 2017

Current Issues in Molecular Biology

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“…Previous studies have shown that CsA ( 1 ) inhibits the influenza A/Puerto Rico/8/34 (H1N1) and the A/WSN/33 (H1N1) with low micromolar EC 50 values (Hamamoto et al, 2013a; Liu et al, 2012). To confirm the antiviral activity of CsA ( 1 ), the MDCK cells were infected with A/WSN/33 (H1N1) at about 100 pfu in the presence of increasing concentrations of CsA ( 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies regarding the mechanism of action of CsA ( 1 ) yielded controversial results (Hamamoto et al, 2013a; Liu et al, 2012). Liu et al showed that CsA ( 1 ) inhibits influenza virus replication via CypA-dependent and -independent pathways (Liu et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…In the CypA-dependent pathway, CsA ( 1 ) enhanced the CypA-mediated influenza M1 protein degradation. However, Hamamoto et al showed that CsA ( 1 ) treatment did not alter the M1 protein level (Hamamoto et al, 2013a). Nevertheless, both studies showed that in CypA knockout or knockdown conditions, CsA ( 1 ) treatment greatly reduced influenza replication, which is consistent with our observation that CsA ( 1 ) inhibition of influenza replication does not require its binding to CypA.…”

Section: Discussionmentioning

confidence: 99%

“…Re-design of CsA ( 1 ) has produced a number of non-immunosuppressive antiviral candidates in clinical trials, such as Alisporivir (Debio-025) and SCY-635 for HCV infection and NIM818 for HIV infection (Peel and Scribner, 2013b). Due to its promising antiviral efficacy, CsA ( 1 ) was also investigated in inhibiting influenza A virus replication and was found to inhibit two influenza A strains, A/WSN/33 (H1N1) and A/Puerto Rico/8/34 (H1N1), with low micromolar EC 50 values (Hamamoto et al, 2013a; Liu et al, 2012). However, it is unknown whether CsA ( 1 ) has broad-spectrum antiviral activity against other influenza A or influenza B viruses, particularly the ones that are currently in circulation.…”

Section: Introductionmentioning

confidence: 99%

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Discovery of cyclosporine A and its analogs as broad-spectrum anti-influenza drugs with a high in vitro genetic barrier of drug resistance

Musharrafieh

et al. 2016

Antiviral Research

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As the number of drug-resistant influenza viruses continues to increase, antivirals with novel mechanisms of action are urgently needed. Among the two classes of FDA-approved antiviral drugs, neuraminidase (NA) inhibitors, oseltamivir, zanamivir, and peramivir, are currently the only choice for the prevention and treatment of influenza virus infection. Due to the antigenic drift and antigenic shift, it will only be a matter of time before influenza viruses become completely resistant to these NA inhibitors. In pursuing the next generation of antiviral drugs with complementary mechanisms of action to those of the NA inhibitors, we have identified a natural product, cyclosporine A (CsA) (1), as a desired drug candidate. In this study, we discovered that CsA (1) and its analogs have broad-spectrum antiviral activity against multiple influenza A and B strains, including strains that are resistant to either NA or M2 inhibitors or both. Moreover, CsA (1) displays a high in vitro genetic barrier of drug resistance than oseltamivir carboxylate Mechanistic studies revealed that CsA (1) acts at the intermediate step of viral replication post viral fusion. Its antiviral mechanism is independent of inhibiting the isomerase activity of cyclophilin A (CypA), and CsA (1) has no effect on the viral polymerase activity The potent antiviral efficacy of CsA (1), coupled with the high in vitro genetic barrier of drug resistance and novel mechanism of action, renders CsA (1) a promising anti-influenza drug candidate for further development.

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Biosurfactants: An Antiviral Perspective

Balakrishnan,

Rameshkumar,

Nivedha

et al. 2023

Multifunctional Microbial Biosurfactants

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Cyclosporin A Inhibits the Propagation of Influenza Virus by Interfering with a Late Event in the Virus Life Cycle

Cited by 21 publications

References 33 publications

Cyclophilin A: A Key Factor in Virus Replication and Potential Target for Anti-viral Therapy

Cyclophilin A: A Key Factor in Virus Replication and Potential Target for Anti-viral Therapy

Discovery of cyclosporine A and its analogs as broad-spectrum anti-influenza drugs with a high in vitro genetic barrier of drug resistance

Biosurfactants: An Antiviral Perspective

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