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

Receptor-binding domain-based subunit vaccines against MERS-CoV

Virus Research
Volume 202, 16 April 2015, Pages 151-159

Naru Zhang, Jian Tang, Lu Lu, Shibo Jiang, Lanying Du

Abstract

Development of effective vaccines, in particular, subunit-based vaccines, against emerging Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) will provide the safest means of preventing the continuous spread of MERS in humans and camels. This review briefly describes the structure of the MERS-CoV spike (S) protein and its receptor-binding domain (RBD), discusses the current status of MERS vaccine development and illustrates the strategies used to develop RBD-based subunit vaccines against MERS. It also summarizes currently available animal models for MERS-CoV and proposes a future direction for MERS vaccines. Taken together, this review will assist researchers working to develop effective and safe subunit vaccines against MERS-CoV and any other emerging coronaviruses that might cause future pandemics.

Keywords

Middle East respiratory syndrome coronavirus, MERS-CoV, Receptor-binding domain, Subunit vaccines

Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections

Microbes and Infection
Volume 17, Issue 2, February 2015, Pages 142-148

Tianlei Ying, Haoyang Li, Lu Lu, Dimiter S. Dimitrov, Shibo Jiang

Abstract

The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak poses a serious threat to public health. Here, we summarize recent advances in identifying human neutralizing monoclonal antibodies (mAbs) against MERS-CoV, describe their mechanisms of action, and analyze their potential for treatment of MERS-CoV infections.

Keywords

Coronavirus, MERS-CoV, mAbs, Receptor binding domain (RBD)