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Antiviral reference standard for the evaluation of new antiviral therapeutics

 

The ZIKA virus (ZIKV) gives rise to a mosquito-borne disease with a variable presentation in different individuals. Although the symptoms are generally mild, the ZIKA virus infection can lead to more serious conditions such as microcephaly in newborns, Guillain-Barré syndrome, neuropathy and myelitis.

There are no vaccines or effective antivirals available for the prevention and treatment of ZIKA-related disease. The research by Taguwa et al (2018) identified heat shock protein inhibitors (HSPs) as an attractive target for the development of effective broad-spectrum antivirals.

Chaperones HSP90 and HSP70 are essential for replication of a set of viruses, including herpes simplex virus 1 and 2, influenza A, enteroviruses, respiratory syncytial virus, hepatitis B and C viruses, Ebola virus, and DENV. In the study cited below, inhibitors of heat shock proteins were tested for their antiviral activity in ZIKV infection models. 

2’-C-methyladenosine (2’CMA) from Carbosynth was used as a positive control for antiviral activity against ZIKV infection in human and mosquito cell lines. 2’CMA is a nucleotide analog and a viral NS5 polymerase inhibitor, which suppresses the viral RNA synthesis in infected host cells. The compound was used as a standard for evaluation and characterization of HSP inhibitors’ antiviral activity in ZIKV infection. 

The HSP70 inhibitors tested were effective in suppressing the production of infectious virions, viral proteins and viral RNA synthesis in three different ZIKV strains of African, Malaysian and Puerto Rican origin. Small-molecule inhibitors of the HSP70 chaperone therefore represent an attractive opportunity for effective antiviral therapeutics especially because the drug resistance phenomena hasn’t been detected.

For more details, read the original paper published in Cell Reports: Taguwa et al., 2018.

 

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