Antiviral activity of K22 against members of the order Nidovirales

Julie Christiane Françoise Rappe,Adriaan De Wilde,Han Di,Christin Müller,Hanspeter Stalder,Philip V’Kovski,Eric Snijder,Margo A Brinton,John Ziebuhr,Nicolas Ruggli,Volker Thiel

doi:10.1016/j.virusres.2018.01.002

Abstract

Recently, a novel antiviral compound (K22) that inhibits replication of a broad range of animal and human coronaviruses was reported to interfere with viral RNA synthesis by impairing double-membrane vesicle (DMV) formation (Lundin et al., 2014). Here we assessed potential antiviral activities of K22 against a range of viruses representing two (sub)families of the order Nidovirales, the Arteriviridae (porcine reproductive and respiratory syndrome virus [PRRSV], equine arteritis virus [EAV] and simian hemorrhagic fever virus [SHFV]), and the Torovirinae (equine torovirus [EToV] and White Bream virus [WBV]).Possible effects of K22 on nidovirus replication were studied in suitable cell lines. K22 concentrations significantly decreasing infectious titres of the viruses included in this study ranged from 25 to 50 μM. Reduction of double-stranded RNA intermediates of viral replication in nidovirus-infected cells treated with K22 confirmed the anti-viral potential of K22. Collectively, the data show that K22 has antiviral activity against diverse lineages of nidoviruses, suggesting that the inhibitor targets a critical and conserved step during nidovirus replication.

Highlights

Possible effects of K22 on nidovirus replication were studied in suitable cell lines
This results in the formation of a reticulo-vesicular network (RVN) that is continuous with the endoplasmic reticulum (ER) and includes double-membrane vesicles (DMV) and convoluted membranes (CM)
Electron microscopic analyses and the observation that K22-resistance can be due to mutations in nsp6 suggest that the antiviral effect of K22 is linked to the inhibition of membrane-bound coronaviruses ribonucleic acid (RNA) synthesis

Summary

Introduction

Possible effects of K22 on nidovirus replication were studied in suitable cell lines. The subgenomic negative-strand RNAs templates the synthesis of subgenomic mRNAs. Positive-stranded RNA viruses are known to induce the formation of replication organelles consisting of modified intracellular host membranes associated with replicative enzyme complexes.

Results

Conclusion