Middle East respiratory syndrome coronavirus infection future or investigational therapies
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Attending to the fact that MERS-CoV is a relatively novel virus, it represents a great challenge since it hasn't been discovered a therapy yet. Currently, numerous studies are being developed in an attempt of finding a treatment approach for MERS. Some of these include the repurpose of previously approved drugs.
Future or Investigational Therapies
The search for broad-spectrum inhibitors aiming to minimize the impact of coronavirus infection remains the major goal. Recent studies are showing the potential use of other drugs and therapies to treat the MERS-CoV, which are based on the experience of treatment of other coronaviruses like the SARS virus. This repurposing of drugs has advantages such as: better availability, lower cost and known safety and tolerability profiles. However, lack of evidence makes these new therapies uncertain.
Cell and animal studies have shown conflicting results: the combination of ribavirin with interferon α-2b in a cell study reduced viral replication; another study in rhesus monkeys with combination of intramuscular ribavirin and interferon α-2b, the group that received the treatment did not develop breathing abnormalities nor radiographic evidence of pneumonia; however, when tried in 5 critically ill patients in Saudi Arabia, this combination was inefficient in all cases, leading to a fatal outcome.
- Convalescent plasma - this therapy, along with others that involve antibodies for the MERS-CoV has the strongest evidence for intervention. Plasma from patients who recovered from MERS-CoV infection contains neutralizing antibodies, which represents the best therapy to neutralize the extracellular virus.
- Interferon - there is supporting evidence from in vitro (SARS virus and MERS-CoV) and in vivo (SARS virus) studies that interferon inhibits viral replication, especially when administered in the early course of the disease. Additionally it is commonly more available than plasma.
- Corticosteroids - there is no evidence of the benefit in the mortality rate and their use is only recommended in a planned treatment regimen or when the benefits of the drug outweigh the potential harms. When used, constant monitoring is mandatory and the ideal timing is the early course of the disease, during the period of maximal inflammatory response.
- Ribavirin - the most commonly used drug in the treatment of SARS. Due to the controversial results of clinical trials relating to the use of ribavirin for MERS and its high level of toxicity in humans, some experts recommend the withhold of the drug.
In Vitro Studies
The development of an antiviral drug is a long-winded process that may not be compatible with the need of a drug to treat coronaviruses, specifically MERS-CoV. Therefore, some studies using existing therapies are being developed in order to find a drug that will likely inhibit the infection by MERS-CoV. One of these studies was performed on cell cultures, in the hope of finding a previously approved FDA compounds that would inhibit the replication of the virus in vitro. It was able to find four molecule inhibitors of the replication of MERS-CoV:
Although the selectivity index of some compounds was limited, the researchers were able to determine a concentration of drug that inhibited the replication of the virus by more than 80%, preserving the viability of the cell. These drugs were also found to be able to inhibit the replication of other coronaviruses, namely the HCoV-229E and the SARS-CoV. The off-label use of these drugs, particularly when used in combination, might be able to reduce the viral load of the host, therefore halting the course of infection and allowing the building of a proper immune response by the host's immune system.
Further studies will evaluate the potential benefit of the combination of 2+ of these drugs, along with interferon as well. Of the above mentioned, the two presenting as better options for more animal studies and/or off-label use, are the chloroquine and lopinavir. This potential use is due to the fact that these drugs were able to inhibit replication of the virus, in the tested cell cultures, in concentrations that are possible to be achieved in the human plasma.
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