Excellent theoretical approach to treating Ebola, from 3 Hong Kong scientists/ BioMedCentral

Just out as a provisional pdf (final version is in production), 3 scientists have reviewed the totality of the published data on Ebola therapeutics, and come up with a framework for combining the use of drugs for their potential synergistic effects.  For me, this put many disparate facts about Ebola into focus, providing much of the context that I had missed. Their tour de force paper was published in an obscure BMC journal, but it is readily available in free full text here.

Most of the drugs (and most are already licensed) that are discussed have been featured in my previous blog posts.  But now there is a more detailed physiologic explanation for how they work and how they might best be combined. Of special interest to me is the potential use of n-acetyl cysteine. This is an extremely safe drug, even at high doses, and is sold as an OTC supplement as well as a licensed drug in the US.

The penultimate page (#38 on the pdf, but pages are not numbered) has a diagram showing which viral and cellular processes are affected by the different drugs.

The paper also includes discussion of vaccines and blood products.  There are 258 references.  This is a must-read for anyone interested in improving Ebola clinical care, or designing Ebola drug trials. Here is the abstract:

Human Ebola Virus Infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus

Kang Yiu Lai, Wing Yiu Ng and Fan Fanny Cheng

Infectious Diseases of Poverty 2014, 3:43  doi:10.1186/2049-9957-3-43

Published: 28 November 2014

Abstract (provisional)

The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.