NM107

1.Nucleoside analogue 2’-C-methylcytidine inhibits hepatitis E virus replication but antagonizes ribavirin    Archives of Virology    2017
Abstract:Hepatitis E virus (HEV) infection has emerged as a global health issue, but no approved medication is available. The nucleoside analogue 2’-C-methylcytidine (2CMC), a viral polymerase inhibitor, has been shown to inhibit infection with a variety of viruses, including hepatitis C virus (HCV). Here, we report that 2CMC significantly inhibits the replication of HEV in a subgenomic replication model and in a system using a full-length infectious virus. Importantly, long-term treatment with 2CMC did not result in a loss of antiviral potency, indicating a high barrier to drug resistance development. However, the combination of 2CMC with ribavirin, an off-label treatment for HEV, exerts antagonistic effects. Our results indicate that 2CMC serves as a potential antiviral drug against HEV infection.
2.Zika Virus: Where Is the Treatment?    Current Treatment Options in Infectious Diseases    2016
Abstract:In the twenty-first century, we have seen the (re-)emergence of several RNA viruses causing severe infections in humans, like SARS and MERS coronavirus, and more recently Ebola virus and Zika virus (ZIKV). A problem with (re-)emerging virus infections is the lack of available medical countermeasures, including antiviral treatment. Therefore, the development of broadly acting antiviral compounds, as well as screening of existing drugs for potential repurposing are explored as ways to fast-track the drug development pipeline for emerging viral diseases. Here, we briefly discuss the available information on potential antiviral treatment of ZIKV infection, as well as specific challenges regarding use of antivirals.
Zika virus is a positive-sense single-stranded RNA arbovirus that belongs to the genus Flavivirus of the family Flaviviridae. Based on nucleotide sequences, ZIKV can be further divided into an African lineage and an Asian lineage. The main vector for ZIKV transmission are Aedes mosquitoes. The first isolation of ZIKV was made in 1947 from serum of a febrile rhesus monkey in the Zika forest of Uganda. During the twentieth century, sporadic human cases of ZIKV infection were reported in Africa caused by the African lineage, and in Asia caused by Asian lineage. The epidemiology of ZIKV changed dramatically in the last decade, when major outbreaks of the Asian lineage of ZIKV were reported on the Island of Yap in 2007 and in French Polynesia in 2013. Subsequently, the Asian lineage of ZIKV spread to the Americas in 2015.