In Vivo Antiviral Effects of U18666A Against Type I Feline Infectious Peritonitis Virus

Abstract

Background: The cationic amphiphilic drug U18666A inhibits the proliferation of type I FIPV in vitro. In this study, we evaluated the in vivo antiviral effects of U18666A by administering it to SPF cats challenged with type I FIPV. Methods: Ten SPF cats were randomly assigned to two experimental groups. FIPV KU-2 were inoculated intraperitoneally to cats. The control group was administered PBS, and the U18666A-treated group was administered U18666A subcutaneously at 2.5 mg/kg on day 0, and 1.25 mg/kg on days 2 and 4 after viral inoculation. Results: Two of the five control cats administered PBS alone developed FIP. Four of the five cats administered U18666A developed no signs of FIP. One cat that temporarily developed fever, had no other clinical symptoms, and no gross lesion was noted on an autopsy after the end of the experiment. The FIPV gene was detected intermittently in feces and saliva regardless of the development of FIP or administration of U18666A. Conclusions: When U18666A was administered to cats experimentally infected with type I FIPV, the development of FIP might be suppressed compared with the control group. However, the number of animals with FIP is too low to establish anti-viral effect of U18666A in cats.

Relation of Dietary Factors with Infection and Mortality Rates of COVID-19 across the World

“…Some of the viral proteins antagonize interferon (INF) and stimulate inflammatory proteins, such as IL-1 family member cytokines ( 23 ). The inflammatory state and pathogenesis of the disease are escalated after abnormal production of cytokines as shown in SARS ( 24 ).…”

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

“…Interestingly, infection by FCoV‐I, the coronavirus species showing the greatest response to remdesivir treatment, was inhibited in host cells pre‐treated with U18666A, a well‐known direct pharmacological inhibitor of the NPC1 protein that is used to induce NPC‐like lysosomal dysfunction, with a resultant lysosomal accumulation of cholesterol and sphingolipids 87,88 . This raises the possibility of a mechanistic convergence or synergy, albeit being a partial one, between the U18666A‐mediated direct inhibition of NPC1, and remdesivir's demonstrated activity against SARS‐CoV‐2, besides its primary mechanism of action being the inhibition of the viral RNA‐dependent RNA polymerase 89 .…”

“…We, therefore, propose evaluating the antiviral potential of U18666A against SARS‐CoV‐2, given its capacity to induce an NPC cellular phenocopy, as an easy starting point to support our hypothesis. Although the safety of U18666A has not been established yet in humans, it has been shown to be without major toxicity in at least two animal models, that is, rats and cats 88,90 …”

The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission

“…U1866A has been shown to inhibit the S protein-driven entry of SARS-CoV, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and the human coronaviruses NL63 and 229E, with the most efficient inhibition observed with SARS-CoV (Wrensch et al, 2014). The antiviral effect of U18666A on type I feline coronavirus (FCoV) has also been characterized in vitro and in vivo (Doki et al, 2020;Takano et al, 2017). We found that, pretreating A549-ACE2 cells 2 h prior to or post infection had no inhibitory effect on Sfull virus ( Figure 3F).…”