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the ''International Severe Acute Respiratory & Emerging Infection Consortium'' (ISARIC), supportive medical care continues to be the approved treatment for [[MERS]]. 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.<ref name="pmid24841273">{{cite journal| author=Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J et al.| title=Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection. | journal=Antimicrob Agents Chemother | year= 2014 | volume= | issue= | pages= | pmid=24841273 | doi=10.1128/AAC.03036-14 | pmc= | url=http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139281416 }} </ref> | the ''International Severe Acute Respiratory & Emerging Infection Consortium'' (ISARIC), supportive medical care continues to be the approved treatment for [[MERS]]. 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.<ref name="pmid24841273">{{cite journal| author=Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J et al.| title=Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection. | journal=Antimicrob Agents Chemother | year= 2014 | volume= | issue= | pages= | pmid=24841273 | doi=10.1128/AAC.03036-14 | pmc= | url=http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139281416 }} </ref> | ||
Cell and animal studies have shown conflicting results: the combination of [[ribavirin]] with [[Interferon-α|interferon α]]-2b in a cell study reduced [[viral replication]]<ref name="pmid23594967">{{cite journal| author=Falzarano D, de Wit E, Martellaro C, Callison J, Munster VJ, Feldmann H| title=Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. | journal=Sci Rep | year= 2013 | volume= 3 | issue= | pages= 1686 | pmid=23594967 | doi=10.1038/srep01686 | pmc=PMC3629412 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23594967 }} </ref>; | Cell and animal studies have shown conflicting results: the combination of [[ribavirin]] with [[Interferon-α|interferon α]]-2b in a cell study reduced [[viral replication]]<ref name="pmid23594967">{{cite journal| author=Falzarano D, de Wit E, Martellaro C, Callison J, Munster VJ, Feldmann H| title=Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. | journal=Sci Rep | year= 2013 | volume= 3 | issue= | pages= 1686 | pmid=23594967 | doi=10.1038/srep01686 | pmc=PMC3629412 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23594967 }} </ref>; another study in rhesus monkeys with combination of [[intramuscular]] [[ribavirin]] and [[Interferon-α|interferon α-2b]], the group that received the treatment did not develop [[breathing]] abnormalities nor [[radiographic]] evidence of [[pneumonia]]<ref name="pmid24013700">{{cite journal| author=Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP et al.| title=Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. | journal=Nat Med | year= 2013 | volume= 19 | issue= 10 | pages= 1313-7 | pmid=24013700 | doi=10.1038/nm.3362 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24013700 }} </ref>; however, when tried in 5 critically ill patients in Saudi Arabia, this combination was inefficient in all cases, leading to a fatal outcome.<ref name="pmid24406736">{{cite journal| author=Al-Tawfiq JA, Momattin H, Dib J, Memish ZA| title=Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. | journal=Int J Infect Dis | year= 2014 | volume= 20 | issue= | pages= 42-6 | pmid=24406736 | doi=10.1016/j.ijid.2013.12.003 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24406736 }} </ref> | ||
Despite the absence of a specific therapy, some approaches are considered to be more worth of experimentation than others. These include:<ref name=ISARIC>{{cite web | title = Treatment of MERS-CoV: Decision Support Tool | url = http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139281416 }}</ref><ref name="pmid23782860">{{cite journal| author=Guery B, van der Werf S| title=Coronavirus: need for a therapeutic approach. | journal=Lancet Infect Dis | year= 2013 | volume= 13 | issue= 9 | pages= 726-7 | pmid=23782860 | doi=10.1016/S1473-3099(13)70153-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23782860 }} </ref><ref name="pmid23549610">{{cite journal| author=Ren Z, Yan L, Zhang N, Guo Y, Yang C, Lou Z et al.| title=The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease. | journal=Protein Cell | year= 2013 | volume= 4 | issue= 4 | pages= 248-50 | pmid=23549610 | doi=10.1007/s13238-013-2841-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23549610 }} </ref><ref name=WHO>{{cite web | title = WHO-ISARIC joint MERS-CoV Outbreak Readiness Workshop: Clinical management and potential use of convalescent plasma | url = http://www.who.int/csr/disease/coronavirus_infections/MERS_outbreak_readiness_workshop.pdf }}</ref><ref name="pmid23993766">{{cite journal| author=Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA| title=Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)--possible lessons from a systematic review of SARS-CoV therapy. | journal=Int J Infect Dis | year= 2013 | volume= 17 | issue= 10 | pages= e792-8 | pmid=23993766 | doi=10.1016/j.ijid.2013.07.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23993766 }} </ref> | Despite the absence of a specific therapy, some approaches are considered to be more worth of experimentation than others. These include:<ref name=ISARIC>{{cite web | title = Treatment of MERS-CoV: Decision Support Tool | url = http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139281416 }}</ref><ref name="pmid23782860">{{cite journal| author=Guery B, van der Werf S| title=Coronavirus: need for a therapeutic approach. | journal=Lancet Infect Dis | year= 2013 | volume= 13 | issue= 9 | pages= 726-7 | pmid=23782860 | doi=10.1016/S1473-3099(13)70153-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23782860 }} </ref><ref name="pmid23549610">{{cite journal| author=Ren Z, Yan L, Zhang N, Guo Y, Yang C, Lou Z et al.| title=The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease. | journal=Protein Cell | year= 2013 | volume= 4 | issue= 4 | pages= 248-50 | pmid=23549610 | doi=10.1007/s13238-013-2841-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23549610 }} </ref><ref name=WHO>{{cite web | title = WHO-ISARIC joint MERS-CoV Outbreak Readiness Workshop: Clinical management and potential use of convalescent plasma | url = http://www.who.int/csr/disease/coronavirus_infections/MERS_outbreak_readiness_workshop.pdf }}</ref><ref name="pmid23993766">{{cite journal| author=Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA| title=Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)--possible lessons from a systematic review of SARS-CoV therapy. | journal=Int J Infect Dis | year= 2013 | volume= 17 | issue= 10 | pages= e792-8 | pmid=23993766 | doi=10.1016/j.ijid.2013.07.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23993766 }} </ref> | ||
Revision as of 02:05, 18 June 2014
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Middle East Respiratory Syndrome (MERS) is a viral respiratory illness. It is caused by an emerging coronavirus, specifically a betacoronavirus called MERS-CoV (Middle East Respiratory Syndrome Coronavirus), first discovered in 2012. Being a relatively novel virus, treatment options are very limited, with no antiviral therapy approved for treating patients yet. Outbreaks of MERS-CoV represent a great challenge since there is very limited time to develop and test new pharmaceutical drugs. Up until now, supportive medical care, along with untested convalescent plasma, have been the only treatment options. However, reuse of drugs for other viruses is presenting as an attractive alternative for MERS-CoV.[1]
Medical Therapy
MERS represents a great challenge in terms of treatment because it is caused by a relatively novel virus to which there is no approved therapy yet. According to the International Severe Acute Respiratory & Emerging Infection Consortium (ISARIC), supportive medical care continues to be the approved treatment for MERS. 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.[1]
Cell and animal studies have shown conflicting results: the combination of ribavirin with interferon α-2b in a cell study reduced viral replication[2]; 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[3]; however, when tried in 5 critically ill patients in Saudi Arabia, this combination was inefficient in all cases, leading to a fatal outcome.[4]
Despite the absence of a specific therapy, some approaches are considered to be more worth of experimentation than others. These include:[5][6][7][8][9]
- 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 the clinical trials relating to use of ribavirin for MERS and its high level of toxicity in humans, some experts recommend withholding the drug.
References
- ↑ 1.0 1.1 Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J; et al. (2014). "Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection". Antimicrob Agents Chemother. doi:10.1128/AAC.03036-14. PMID 24841273.
- ↑ Falzarano D, de Wit E, Martellaro C, Callison J, Munster VJ, Feldmann H (2013). "Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin". Sci Rep. 3: 1686. doi:10.1038/srep01686. PMC 3629412. PMID 23594967.
- ↑ Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP; et al. (2013). "Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques". Nat Med. 19 (10): 1313–7. doi:10.1038/nm.3362. PMID 24013700.
- ↑ Al-Tawfiq JA, Momattin H, Dib J, Memish ZA (2014). "Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study". Int J Infect Dis. 20: 42–6. doi:10.1016/j.ijid.2013.12.003. PMID 24406736.
- ↑ "Treatment of MERS-CoV: Decision Support Tool".
- ↑ Guery B, van der Werf S (2013). "Coronavirus: need for a therapeutic approach". Lancet Infect Dis. 13 (9): 726–7. doi:10.1016/S1473-3099(13)70153-1. PMID 23782860.
- ↑ Ren Z, Yan L, Zhang N, Guo Y, Yang C, Lou Z; et al. (2013). "The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease". Protein Cell. 4 (4): 248–50. doi:10.1007/s13238-013-2841-3. PMID 23549610.
- ↑ "WHO-ISARIC joint MERS-CoV Outbreak Readiness Workshop: Clinical management and potential use of convalescent plasma" (PDF).
- ↑ Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA (2013). "Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)--possible lessons from a systematic review of SARS-CoV therapy". Int J Infect Dis. 17 (10): e792–8. doi:10.1016/j.ijid.2013.07.002. PMID 23993766.