Coronavirus biology: where products in clinical testing intervene
An overview of how therapies in clinical trials for coronavirus interfere with viral biology
The 13 therapies in clinical trials to treat coronavirus map to at least half a dozen mechanisms, intervening at three different steps in the viral cycle or manipulating different aspects of the host immune response.
As of Feb. 7, 13 clinical trials to treat 2019-nCoV acute respiratory disease have been registered on ClinicalTrials.gov, and another 19 have been listed on the Chinese Clinical Trial Register. The count excludes traditional Chinese medicines and intravenous immunoglobulin therapies not known to come from individuals who recovered from 2019-nCoV infection (see “Clinical Trials for Coronavirus Have Begun”).
All but one of these therapies are already approved for other infections, and their sponsors are hoping their mechanisms are applicable to 2019-nCoV.
The most common MOAs are inhibitors of viral proteases or RNA synthesis (see: Figure “Where Clinical Interventions Hit 2019-nCoV Biology”).
Gilead Sciences Inc. (NASDAQ:GILD) has the largest number of therapies in testing for the virus, at three. It also has the only non-approved therapy in the clinic: the nucleotide analog remdesivir.
On Tuesday, a draft report of WHO’s R&D Blueprint Clinical Trials expert group named Gilead’s remdesivir the most promising 2019-nCoV candidate. The therapy reduced infection in monkey kidney cells with an EC50 of 0.77 μM and was effective in human cells at concentrations as low as 0.21 μM (see "WHO Prioritizing Gilead’s Remdesivir" and "Gilead’s Remdesivir vs. 2019-nCov in Cells").
Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus. The 2019nCoV content is free to all who visit the site.
Figure: Where clinical interventions hit 2019-nCoV biology
A depiction of where therapies in clinical trials for 2019-nCoV acute respiratory disease intersect viral biology or host immunity. Not shown are cell and microbiome transplants, traditional Chinese medicines, and intravenous immunoglobulin therapies not known to come from individuals who recovered from 2019-nCoV infection. Source: BCIQ: BioCentury Online Intelligence, company websites, scientific literature
3CLpro (NSP5) - 3C-like proteinase
IFNα - Interferon α
TLR2 - Toll-like receptor 2
TLR9 - Toll-like receptor 9