A clinical stage LMW-DS drug inhibits infection of human cells by Dengue, Zika and Yellow Fever viruses

Abstract

The flavivirus family are responsible for the most abundant arboviral diseases of humans in terms of geographical distribution, morbidity and mortality; at least 2.5 billion people are at risk with, for example, an estimated 100-400 million Dengue infections a year. However, for infections by Dengue, Zika or Yellow Fever virus there are no effective anti-infective drug treatments nor for Dengue or Zika virus a safe effective vaccine and prevention at present focusses on vector (mosquito) control. Whilst symptoms from Dengue, Zika and Yellow Fever virus infection may be mild for some, they are very serious and life threatening for others. For instance, severe Dengue is a leading cause of hospitalisation and death among children and adults in Asian and Latin American countries. Likewise, Zika infection can have catastrophic consequences for pregnant women following the passing of the virus to their foetus with arising miscarriage or birth defects including microcephaly that can be fatal. The aim of the present study was to evaluate the potential of a unique low molecular weight dextran sulphate (LMW-DS) clinical stage drug, ILB(R), to inhibit infection of human cells by four serotypes of Dengue virus (DENV1-4), two strains of Zika virus (African and Asian) and Yellow Fever virus (vaccine strain YF17D) assessed by immunofluorescence of viral particles. ILB(R) potently inhibited infection by all the strains of Dengue, Zika and Yellow Fever virus in a concentration-dependent manner with IC50 for ILB(R) ranging from 31 to 343 g/ml. In conclusion, given the safety profile of ILB(R) established in a number of Phase I and Phase II clinical trials, these results highlight the potential of ILB(R) to treat patients infected with Dengue, Zika or Yellow Fever virus with the opportunity to translate the findings quickly by clinical investigation.