Therapeutic potential for clomiphene, a selective estrogen receptor modulator, in the treatment of COVID‐19

Ghasemnejad Berenji, M and Pashapour, S and Ghasemnejad Berenji, H (2020) Therapeutic potential for clomiphene, a selective estrogen receptor modulator, in the treatment of COVID‐19. Medical Hypotheses, 145. pp. 1-3.

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Abstract

A novel coronavirus disease 2019 (COVID-19) outbreak is a global concern that has immeasurably impacted mankind's life. At present, there is no approved therapeutics available to treat this infection and only the symptomatic management is the base of clinical treatment [1]. Since, the drug development is a time-consuming process, repurposing the use of an old drug with low adverse effects to treat new infection could be a reasonable strategy to reduce the massive health and economic burden of the COVID-19 pandemic. The classical method to develop an antiviral agent is based on drugs affecting the functions of viral proteins that play essential role in the viral life cycles [2]. Clomiphene is a non‐steroidal triphenylethylene derivative belongs to a group of drugs known as selective estrogen receptor modulators (SERMs) which exerts both estrogenic agonist and estrogenic antagonist effects. This drug is used to treat female infertility due to anovulation. Furthermore, clomiphene is an efficient drug for reversing the impotence in men with hypogonadism due to low testosterone secretion [3]. Previous studies have shown that clomiphene has antiviral effects against Ebola virus. Screening studies for drug repurposing as antivirals indicated that the antiviral effect of clomiphene is related to cell-based mechanisms independent to the classical estrogen signaling pathway. In fact, this drug would interfere with a late stage of Ebola virus entry into target cells, likely affecting the triggering of fusion of the viral envelope with the endosomal limiting membrane. This drug showed EC50 values of 11 and 3.8 μM against the two strains EBOV-95 and EBOV-76, respectively, and a 90% of survival benefit for infected mice [4]. SARS-COV-2 is a lipid-enveloped virus encounter the endosomal/lysosomal host compartment in a critical step of infection [5]. Niemann-Pick type C (NP-C) disease is a rare neurodegenerative disease caused by de

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