Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission

Abstract

Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/β and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1β, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.

Ebselen derivatives are very potent dual inhibitors of SARS-CoV-2 proteases - PLproand Mproin in vitro studies

“…The efficacy of ebselen and other organoselenium compounds has been previously evaluated for HIV 30,31 , HSV2 32 , HCV 33 , and Zika virus 34 infections. Moreover, a recent report presents ebselen and its derivatives as potent inhibitors of SARS-CoV-2 PL pro .…”

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

“…Simanjuntak and colleagues demonstrated that ZIKV-infected testicles presented progressive damage with a significant oxidative microenvironment, with high levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4 and pro-inflammatory cytokines as IL-1β, IL-6, and G-CSF. They proposed the use of the antioxidant ebselen (EBS) to prevent the sexual transmission of the virus and to improve host testicular immune response [123].…”

Host-Directed Antivirals: a Realistic Alternative to Fight Zika Virus

“…Ebselen (EBS), an antioxidant that reduces oxidative stress and improves histopathological features in a testicular injury study model and is currently in clinical trials for various diseases, showed minor effects in reducing ZIKV progeny production and viral E protein expression and on overall survival and viremia level of challenged AG129 mice; however, the drug significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration, and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a model of male-to-female mouse sperm transfer [128].…”