May 29, 2014

expert reaction to identification of new coronavirus inhibitor, as published in PLOS Pathogens

A paper published in PLOS Pathogens reported to have identified a new coronavirus inhibitor, K22, which acts to impede viral production in host cells and could be effective against SARS, MERS and other coronaviruses.

Dr Jake Dunning, Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, said:

“The findings of this study are welcomed. The research group has identified a potential therapeutic target in MERS-CoV infection and they have increased our understanding of coronavirus biology. The number of agents screened was impressive. The fact that K22 has activity against a number of different coronaviruses is exciting, since we can expect to see infections caused by new coronaviruses in the future. This group and others (e.g. http://www.silver-europe.com/spip.php?article229 and http://aac.asm.org/content/early/2014/05/13/AAC.03036-14.long) are doing important preliminary work in identifying potential treatments and they have responded quickly, following the first MERS-CoV infections in humans. Some antiviral screening studies have included established medicines that are used to treat other conditions. This is sensible because previous experience of using a particular treatment means that we already have an idea about how that medicine behaves in humans.

“As the authors of this study point out, identification of an agent with antiviral activity in vitro (including the testing of agents in infected human airway cells in the lab) is some way from having a medicine available for the treatment of actual patients. The next step will be to test such agents, alone and in combination with other potential treatments, in an appropriate animal model of infection. Of course, animal models do not always predict the effectiveness and safety or tolerability of a new treatment in humans; it’s only when clinical trials have been conducted that we can begin to evaluate a new treatment for infection in humans. We also need to ask whether equivalent levels of an identified agent can be achieved safely in patients. When developing new treatments, it is also important to consider application to real-world scenarios. For example, will a proposed treatment remain effective when it is used in patients who have been infected for some time, patients who have already developed severe illness?

“Even if MERS-CoV does not take off in the way that SARS did, we do need effective treatments for MERS and other coronavirus infections. Groups such as ISARIC and PHE continue to evaluate results from studies as they are published, as well as looking at data on treatments that were tried for SARS. Current treatment options for MERS remain limited, however (http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139281416). Two years have passed since MERS-CoV caused the first outbreak in Jordan and we need to accelerate research efforts at all levels. An important next step for public health is to set research priorities for developing new treatments that target the virus and also the immune response to infection, and to identify the most promising, clinically feasible agents to take forward to animal studies and rapid clinical trials.”
Prof Ian Jones, Professor of Virology, University of Reading, said:

“This paper is interesting from a basic science point of view, but is currently nowhere near clinical drug development. The study has identified a potential point of weakness that may be common to all coronaviruses, however there is no clinically relevant data and no information about potential toxicity of K22, so at this stage we just don’t know whether this could ever have potential as a drug treatment of coronaviruses.”
Dr Ben Neuman, a virologist at the University of Reading, said:

“The most interesting aspect of this drug is the way it works. Before a virus like MERS can multiply, it usually sets up a sort of virus-making factory in the cell. Most drugs will target a single machine in that factory at a time, but it can be difficult to block all the machines at once, which is why it is difficult to cure a virus with a single drug. This new chemical appears to attack the factory itself – an interesting approach that might work well in a multi-pronged antiviral therapy. This is not an immediate cure for MERS, though compounds like this may one day be useful in drug cocktails like the ones we use to treat HIV. ”

‘Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the Middle East Respiratory Syndrome virus’ by Anna Lundin et al. published in PLOS Pathogens on Thursday 29 May 2014

Declared interests

Jake Dunning helps develop guidance on potential treatment options for MERS-CoV infection and is a member of the International Severe Acute Respiratory and emerging Infections Consortium (www.isaric.org).