Tilorone: a Broad-Spectrum Antiviral Invented in the USA and Commercialized in Russia and beyond

Pharmaceutical research
Volume 37, 2020, Issue 4, 71

Ekins, S.; Lane, T. R.; Madrid, P. B.

Abstract

For the last 50 years we have known of a broad-spectrum agent tilorone dihydrochloride (Tilorone). This is a small-molecule orally bioavailable drug that was originally discovered in the USA and is currently used clinically as an antiviral in Russia and the Ukraine. Over the years there have been numerous clinical and non-clinical reports of its broad spectrum of antiviral activity. More recently we have identified additional promising antiviral activities against Middle East Respiratory Syndrome, Chikungunya, Ebola and Marburg which highlights that this old drug may have other uses against new viruses. This may in turn inform the types of drugs that we need for virus outbreaks such as for the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tilorone has been long neglected by the west in many respects but it deserves further reassessment in light of current and future needs for broad-spectrum antivirals.

Keywords

Antiviral, broad spectrum, interferon inducers, respiratory virus infections

Inhibitors of SARS-CoV entry – Identification using an internally-controlled dual envelope pseudovirion assay

Antiviral Research
Volume 92, Issue 2, November 2011, Pages 187-194

Yanchen Zhou, Juliet Agudelo, KaiLu, David H.Goetz Elizabeth Hansell, Yen Ting Chen William R.Roush, James McKerrow, Charles S.Craik, Sean M.Amberg, Graham Simmons

Abstract

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes.

Keywords

Inhibitors of SARS-CoV entry, Antiviral, HTS, High-throughput screening, Dual envelope pseudovirion assay, Pseudovirus