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Sensitivity of SARS/MERS CoV to interferons and other drugs based on achievable serum concentrations in humans
David R Strayer, Robert Dickey, William A Carter1
1Hemispherx Biopharma, Inc., Philadelphia, PA 19103, USA. david.strayer@hemispherx.net.
Abstract:
A novel coronavirus (MERS-CoV) related to SARS-CoV recently emerged in the Middle East causing more than 400 deaths with a mortality rate of about 30%, much higher than SARS-CoV. Both viruses target epithelial cells in the respiratory tract, although utilizing different cellular receptors. Because of the sporadic nature of the MERS outbreak and difficulty in collecting randomized, controlled clinical data, the objective of this review was to focus on published in vitro and in vivo drug sensitivity data using both cell lines and available animal models of SARS/MERS CoV infection. Determination of drug activity was based on achievable serum levels in humans relative to in vitro IC50 (50% inhibitory concentration) or EC50 (50% effective concentration) drug concentrations. The most active drugs against SARS/MERS CoV at clinically achievable serum levels were type I interferons and a TLR3 agonist, interferon inducer/activator.
Insights
This review identifies effective drugs against Middle East Respiratory Syndrome-associated Coronavirus (MERS-CoV). Type I interferons and a TLR3 agonist show promise for MERS-CoV treatment based on in vitro and in vivo studies.
Area of Science:
- Virology
- Infectious Diseases
- Pharmacology
Background:
- Middle East Respiratory Syndrome-associated Coronavirus (MERS-CoV), a novel coronavirus, has emerged with a high mortality rate.
- Both MERS-CoV and SARS-CoV infect respiratory tract epithelial cells but use different receptors.
- Challenges in clinical data collection for MERS-CoV necessitate alternative methods to assess drug efficacy.
Purpose of the Study:
- To review in vitro and in vivo drug sensitivity data for SARS-CoV and MERS-CoV.
- To identify drugs effective against MERS-CoV at clinically achievable serum concentrations.
Main Methods:
- Analysis of published in vitro drug sensitivity data (IC50/EC50).
- Evaluation of in vivo data from available animal models of SARS/MERS-CoV infection.
- Comparison of drug activity with achievable human serum levels.
Main Results:
- Type I interferons demonstrated significant activity against SARS/MERS-CoV.
- A TLR3 agonist, functioning as an interferon inducer/activator, was also highly effective.
- These drugs showed efficacy at concentrations achievable in human serum.
Conclusions:
- Type I interferons and TLR3 agonists are promising therapeutic candidates for MERS-CoV.
- Further research into these agents could lead to effective MERS-CoV treatments.
- In vitro and in vivo data provide valuable insights for drug development against emerging coronaviruses.
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