Identification of IMP Dehydrogenase as a Potential Target for Anti-Mpox Virus Agents

Hishiki, Takayuki; Morita, Takeshi; Akazawa, Daisuke; Ohashi, Hirofumi; Park, Eun-Sil; Kataoka, Michiyo; Mifune, Junki; Shionoya, Kaho; Tsuchimoto, Kana; Ojima, Shinjiro; Azam, Aa Haeruman; Nakajima, Sachiko; Kawahara, Madoka; Yoshikawa, Tomoki; Shimojima, Masayuki; Kiga, Kotaro; Maeda, Ken; Suzuki, Tadaki; Ebihara, Hideki; Takahashi, Yoshimasa; Watashi, Koichi

doi:10.1128/spectrum.00566-23

Cited by 5 publications

(3 citation statements)

References 47 publications

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“…However, an intercell type variation in efficacy of TFT could be observed (Figure 1C). In DF, TFT inhibited mpox virus with IC 50 values comparable to previously described TFT efficacy in Vero cells 10 as well as against other orthopoxviruses. 11 In contrast, TFT displayed twofold lower potency in keratocytes (mean IC 50 values 1.11 µM) and HConEpiC (mean IC 50 values 0.95 µM) in comparison to DF (mean IC 50 values 0.42 µM).…”

Section: Tft Efficacy In Ophthalmic Cell Modelssupporting

confidence: 80%

“…TFT is a nucleoside analog, which has been approved for other ophthalmic conditions like herpes simplex keratitis 2 . A recent in vitro study demonstrated the antiviral efficacy of TFT against mpox infection in Vero cells 10 . However, the efficacy of antiviral drugs may differ between laboratory cell lines and primary cells derived from relevant tissues 17,18 .…”

Section: Discussionmentioning

confidence: 99%

“…2 A recent in vitro study demonstrated the antiviral efficacy of TFT against mpox infection in Vero cells. 10 However, the efficacy of antiviral drugs may differ between laboratory cell lines and primary cells derived from relevant tissues. 17,18 Here, we show that TFT inhibits infection of a broad range of mpox isolates in cell models relevant for ophthalmic manifestations, albeit with lower efficacy than in dermal cells.…”

Section: Discussionmentioning

confidence: 99%

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Trifluridine for treatment of mpox infection in drug combinations in ophthalmic cell models

Cinatl,

Bechtel,

Reus

et al. 2024

Journal of Medical Virology

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The Mpox virus can cause severe disease in the susceptible population with dermatologic and systemic manifestations. Furthermore, ophthalmic manifestations of mpox infection are well documented. Topical trifluridine (TFT) eye drops have been used for therapy of ophthalmic mpox infection in patients, however, its efficacy against mpox virus infection in this scenario has not been previously shown. In the present study, we have established ophthalmic cell models suitable for the infection with mpox virus. We show, that TFT is effective against a broad range of mpox isolates in conjunctival epithelial cells and keratocytes. Further, TFT remained effective against a tecovirimat‐resistant virus strain. In the context of drug combinations, a nearly additive effect was observed for TFT combinations with brincidofovir and tecovirimat in conjunctival epithelial cells, while a slight antagonism was observed for both combinations in keratocytes. Altogether, our findings demonstrate TFT as a promising drug for treatment of ophthalmic mpox infection able to overcome tecovirimat resistance. However, conflicting results regarding the effect of drug combinations with approved compounds warrant close monitoring of such use in patients.

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Section: Tft Efficacy In Ophthalmic Cell Modelssupporting

confidence: 80%