Be vigilant: New MERS-CoV outbreaks can occur in the Kingdom of Saudi Arabia

Salamati, Payman; Razavi, Seyed Mohsen

doi:10.1016/j.tmaid.2015.03.013

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…MERS is an acute respiratory disease and often leads to pneumonia and renal failure, very similar to severe acute respiratory syndrome (SARS), a worldwide epidemic in 2003 caused by another coronavirus, SARS-CoV [1][2][3][4][5]. Most MERS cases have been found in countries of the Middle East, including Saudi Arabia, Qatar, and the United Arab Emirates [6][7][8][9][10]. However, a most recent MERS outbreak occurred in South Korea, where 186 cases could all be traced back to a 68year-old South Korean man travelling from the Middle East [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

MERS-CoV spike protein: a key target for antivirals

Yang

Zhou

et al. 2016

Expert Opinion on Therapeutic Targets

263

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Introduction The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered This review illustrates MERS-CoV S protein’s structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides. Expert opinion No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb’s limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.

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Section: Introductionmentioning

confidence: 99%

MERS-CoV spike protein: a key target for antivirals

Yang

Zhou

et al. 2016

Expert Opinion on Therapeutic Targets

263

295

View full text Add to dashboard Cite

show abstract

“…As of June 2017, the World Health Organization (WHO) has been notified of 2037 laboratory-confirmed cases of infection with MERS-CoV and at least 710 deaths related to MERS-CoV, showing a much higher fatality rate (about 35%) [ 7 ] compared to SARS-CoV (less than 10%) [ 2 , 3 ]. Since September 2012, 27 countries have reported cases of MERS-CoV globally while most cases were found in Saudi Arabia [ 8 , 9 ]. Various therapeutics including peptide inhibitors, neutralizing antibodies, and vaccines are under development for the treatment and prevention of MERS-CoV [ 10 , 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus

Sun

Zhang

Shi

et al. 2017

Viruses

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The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (KD) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC50) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent.

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Be vigilant: New MERS-CoV outbreaks can occur in the Kingdom of Saudi Arabia

Cited by 2 publications

References 6 publications

MERS-CoV spike protein: a key target for antivirals

MERS-CoV spike protein: a key target for antivirals

Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus

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