Cyclophilins and cyclophilin inhibitors in nidovirus replication

Wilde, Adriaan H. de; Pham, Uyen; Posthuma, Clara C.; Snijder, Eric J.

doi:10.1016/j.virol.2018.06.011

Cited by 66 publications

(76 citation statements)

References 139 publications

(176 reference statements)

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“…Finally, as expected, the non-immunosuppressive cyclosporin A analogue alisporivir inhibited SARS-CoV-2 replication, as demonstrated previously for SARS-CoV and MERS-CoV [58]. Although the exact mode of action of this inhibitor is unclear, it is thought to modulate CoV interactions with members of the cyclophilin family [108]. Unfortunately, all of these in vitro antiviral activities should probably be classified as modest, emphasizing the urgency of large-scale drug repurposing and discovery programmes that target SARS-CoV-2 and coronaviruses at large.…”

Section: Discussionsupporting

confidence: 80%

SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology

Ogando

Dalebout

Zevenhoven-Dobbe

et al. 2020

Journal of General Virology

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519

522

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The sudden emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 from the Chinese province of Hubei and its subsequent pandemic spread highlight the importance of understanding the full molecular details of coronavirus infection and pathogenesis. Here, we compared a variety of replication features of SARS-CoV-2 and SARS-CoV and analysed the cytopathology caused by the two closely related viruses in the commonly used Vero E6 cell line. Compared to SARS-CoV, SARS-CoV-2 generated higher levels of intracellular viral RNA, but strikingly about 50-fold less infectious viral progeny was recovered from the culture medium. Immunofluorescence microscopy of SARS-CoV-2-infected cells established extensive cross-reactivity of antisera previously raised against a variety of non-structural proteins, membrane and nucleocapsid protein of SARS-CoV. Electron microscopy revealed that the ultrastructural changes induced by the two SARS viruses are very similar and occur within comparable time frames after infection. Furthermore, we determined that the sensitivity of the two viruses to three established inhibitors of coronavirus replication (remdesivir, alisporivir and chloroquine) is very similar, but that SARS-CoV-2 infection was substantially more sensitive to pre-treatment of cells with pegylated interferon alpha. An important difference between the two viruses is the fact that – upon passaging in Vero E6 cells – SARS-CoV-2 apparently is under strong selection pressure to acquire adaptive mutations in its spike protein gene. These mutations change or delete a putative furin-like cleavage site in the region connecting the S1 and S2 domains and result in a very prominent phenotypic change in plaque assays.

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Section: Discussionsupporting

confidence: 80%

SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology

Ogando

Dalebout

Zevenhoven-Dobbe

et al. 2020

Journal of General Virology

Self Cite

519

522

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“…Cyclophilins are a class of highly conserved cellular proteins, which have specific chemical structures containing 109 amino acids and could interact with other proteins from different locations and of multiple functions [14,15]. Previous reports indicated the main functions of cyclophilins was protein folding and trafficking [16].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

Wang

Yue³

et al. 2019

J Ovarian Res

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Ovarian cancer (OC) is a type of gynaecological malignancy with high mortality in females. Serous ovarian cancer (SOC) is a distinct subtype of OC with poor early diagnosis. Given the limitations of traditional therapies, such as chemotherapy, targeted treatment is therefore a promising therapy to improve the survival rate of SOC patients. Cyclophilin A (CYPA) is a member of Cyclophilin family and thought to participates in multiple cellular processes such as cell transduction and immune modulation. Recently, various of studies indicated that CYPA has critical impact on cancer progression. CYPA could regulate cell proliferation, invasion, and chemoresistance of multiple types of cancers. However, it is still unclear whether it could affect ovarian cancer. In this study, we demonstrated that CYPA was highly expressed in SOC tissues compared with adjacent tissues. Further, CYPA was significantly associated with clinical stage and lymphnode metastasis of SOC patients. Additionally, data indicated that knockdown of CYPA by its shRNA dramatically reduces migration and invasion capacity of SOC cells in vitro and blocks tumor metastasis in vivo. Our study investigates the involvement of CYPA in the progression and metastasis of SOC, and therefore provides CYPA as a promising therapeutic target for SOC treatment.

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“…Finally, as expected, the non-immunosuppressive cyclosporin A analogue Alisporivir inhibited SARS-CoV-2 replication, as demonstrated previously for SARS-CoV and MERS-CoV (58). Although the exact mode of action of this inhibitor it is unclear, it is thought to modulate CoV interactions with members of the cyclophilin family (108). Unfortunately, all of these in vitro antiviral activities should probably be classified as modest, emphasizing the urgency of large-scale drug repurposing and discovery programmes that target SARS-CoV-2 and coronaviruses at large.…”

Section: Discussionmentioning

confidence: 99%

SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology

Ogando

Dalebout

Zevenhoven-Dobbe

et al. 2020

Preprint

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35 36 The sudden emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 37 at the end of 2019 from the Chinese province of Hubei and its subsequent pandemic spread 38 highlight the importance of understanding the full molecular details of coronavirus infection 39 and pathogenesis. Here, we compared a variety of replication features of SARS-CoV-2 and 40 SARS-CoV and analysed the cytopathology caused by the two closely related viruses in the 41 commonly used Vero E6 cell line. Compared to SARS-CoV, SARS-CoV-2 generated higher 42 levels of intracellular viral RNA, but strikingly about 50-fold less infectious viral progeny was 43 recovered from the culture medium. Immunofluorescence microscopy of SARS-CoV-2-44 infected cells established extensive cross-reactivity of antisera previously raised against a 45 variety of nonstructural proteins, membrane and nucleocapsid protein of SARS-CoV. Electron 46 microscopy revealed that the ultrastructural changes induced by the two SARS viruses are 47

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Cyclophilins and cyclophilin inhibitors in nidovirus replication

Cited by 66 publications

References 139 publications

SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology

SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology

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