MERS-CoV spike protein: Targets for vaccines and therapeutics

Antiviral Research
Volume 133, September 2016, Pages 165-177

Qihui Wang, Gary Wong, Guangwen Lu, Jinghua Yan, George F. Gao

Abstract

The disease outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) is still ongoing in the Middle East. Over 1700 people have been infected since it was first reported in September 2012. Despite great efforts, licensed vaccines or therapeutics against MERS-CoV remain unavailable. The MERS-CoV spike (S) protein is an important viral antigen known to mediate host-receptor binding and virus entry, as well as induce robust humoral and cell-mediated responses in humans during infection. In this review, we highlight the importance of the S protein in the MERS-CoV life cycle, summarize recent advances in the development of vaccines and therapeutics based on the S protein, and discuss strategies that can be explored to develop new medical countermeasures against MERS-CoV.

Keywords

Coronavirus, MERS-CoV, Spike protein, Vaccines, Therapeutics, Animal models

Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond

Trends in Microbiology
Volume 23, Issue 8, August 2015, Pages 468-478

Guangwen Lu, Qihui Wang, George F. Gao

Abstract

Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that crossed the species barriers to infect humans. The mechanism of viral interspecies transmission is an important scientific question to be addressed. These coronaviruses contain a surface-located spike (S) protein that initiates infection by mediating receptor-recognition and membrane fusion and is therefore a key factor in host specificity. In addition, the S protein needs to be cleaved by host proteases before executing fusion, making these proteases a second determinant of coronavirus interspecies infection. Here, we summarize the progress made in the past decade in understanding the cross-species transmission of SARS-CoV and MERS-CoV by focusing on the features of the S protein, its receptor-binding characteristics, and the cleavage process involved in priming.

Keywords

coronavirus, interspecies transmission, viral and host determinants, spike (S), SARS-CoV, MERS-CoV

Middle East Respiratory Syndrome Coronavirus “MERS-CoV”: Current Knowledge Gaps

Paediatric Respiratory Reviews
Volume 16, Issue 3, June 2015, Pages 197-202

G. R. Banik, G. Khandaker, H. Rashid

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) that causes a severe lower respiratory tract infection in humans is now considered a pandemic threat to the Gulf region. Since its discovery in 2012, MERS-CoV has reached 23 countries affecting about 1100 people, including a dozen children, and claiming over 400 lives. Compared to SARS (severe acute respiratory syndrome), MERS-CoV appears to kill more people (40% versus 10%), more quickly, and is especially more severe in those with pre-existing medical conditions. Most MERS-CoV cases (>85%) reported thus far have a history of residence in, or travel to the Middle East. The current epidemiology is characterised by slow and sustained transmission with occasional sparks. The dromedary camel is the intermediate host of MERS-CoV, but the transmission cycle is not fully understood. In this current review, we have briefly summarised the latest information on the epidemiology, clinical features, diagnosis, treatment and prevention of MERS-CoV especially highlighting the knowledge gaps in its transmission dynamics, diagnosis and preventive strategy.

Keywords

Dromedary, MERS-CoV, Middle East, Respiratory tract infection, SARS, Transmission chain

Development of animal models against emerging coronaviruses: From SARS to MERS coronavirus

Virology
Volumes 479–480, May 2015, Pages 247-258

Troy C. Sutton, Kanta Subbarao

Abstract

Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV.

Keywords

Coronaviruses, SARS-CoV, MERS-CoV, Animal models, Receptor

Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV)

Genomics, Proteomics & Bioinformatics
Volume 1, Issue 4, November 2003, Pages 247-262

Ken Yan Ching Chow, Chung Chau Hon, Raymond Kin Hi Hui, Raymond Tsz Yeung Wong, Chi Wai Yip, Fanya Zeng, Frederick Chi Ching Leung

Abstract

The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identification of the agent represented an important breakthrough, our understanding of the deadly virus remains limited. Detailed biological knowledge is crucial for the development of effective countermeasures, diagnostic tests, vaccines and antiviral drugs against the SARS-CoV. This article reviews the present state of molecular knowledge about SARS-CoV, from the aspects of comparative genomics, molecular biology of viral genes, evolution, and epidemiology, and describes the diagnostic tests and the anti-viral drugs derived so far based on the available molecular information.

Key words

severe acute respiratory syndrome, SARS-CoV, genome, phylogenetics, human leukocyte antigen (HLA) system, molecular epidemiology