Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD
CELL REPORTS
Authors: Wang, Nianshuang; Rosen, Osnat; Wang, Lingshu; Turner, Hannah L.; Stevens, Laura J.; Corbett, Kizzmekia S.; Bowman, Charles A.; Pallesen, Jesper; Shi, Wei; Zhang, Yi; Leung, Kwanyee; Kirchdoerfer, Robert N.; Becker, Michelle M.; Denison, Mark R.; Chappell, James D.; Ward, Andrew B.; Graham, Barney S.; McLellan, Jason S.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV.
Seroprevalence of Middle East Respiratory Syndrome Corona Virus in dromedaries and their traders in upper Egypt
JOURNAL OF INFECTION IN DEVELOPING COUNTRIES
Authors: Sayed, Amal S. M.; Malek, Safaa S.; Abushahba, Mostafa F. N.
Abstract
Introduction: Camel trade in Egypt depends mainly on importation. Seemingly healthy imported camels are responsible for the ingress of serious diseases into Egypt. A striking example of this concerning public health globally is the Middle East respiratory coronavirus (MERS-CoV) which causes case fatalities of over 34%. Here, we detennined the seroepidemiological situation of the MERS-CoV in imported camels and their traders in Upper Egypt. Methodology: Sera of sixty-three dromedaries and twenty-eight camel traders were recruited (January 2015-December 2016). The age, gender, and sampling locality of each sampled camel and human were obtained. Semi-quantitative anti-MERS-CoV IgG ELISAs which utilize the purified spike protein domain Si antigen of MERS coronavirus (MERS-CoV S1) were used to detect specific IgG antibodies against the virus. Results: The data showed that 58.73% of imported camels and 25% of traders had antibodies specific to MERS-CoV. Interestingly, like seroreactive camels, all seropositive humans were apparently healthy without any history of developing severe respiratory disease in the 14 days prior to sampling. Having specific antibodies among the examined camel sera was significantly different (P < 0.0001) in relation to various sampling localities, gender and age groups. In contrast, the seropositivity rate of MERS-CoV IgG in humans did not differ significantly by any of the studied factors. Conclusions: The current study provides the first serological evidence of occupational exposure of humans to MERS-CoV in Africa. Additionally, it reports that imported camels could be implicated in introducing MERS-CoV into Egypt. Accordingly, application of strict control measures to camel importation is a priority.