by Cross-competition SPR assay was used to investigate the epitopes region; LCA57, LCA60, 3B11 antibodies and CD26 receptor (ligands) were first immobilized on different channels (vertical column) of the SPR chip. and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses. Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emergent subgroup C betacoronavirus that was detected for the first times in June and September of 2012, when two cases of severe infections were identified in the Eastern Mediterranean region (1,2). As of June 29, 2015, 1,379 human infections with 531 deaths have been confirmed in 26 countries in the Middle East, Europe, North Africa, Asia, and Americas, including the recent outbreak in South Korea caused by an Tepilamide fumarate individual Tepilamide fumarate who traveled to the Middle East, which caused 164 infections and 23 deaths (www.ecdc.europa.eu). MERS-CoV causes severe infection of the lower respiratory tract, similar to the Severe Acute Respiratory Syndrome CoV (SARS-CoV) that appeared in China in 2002. Several cases of human-to-human transmission have been reported in health care workers and family clusters, but at the current time there is no evidence of sustained human-to-human transmission. SARS-CoV and MERS-CoV belong to the B and C betacoronavirus lineages and have been shown to bind to cellular receptors ACE2 and CD26 [also known as dipeptidyl peptidase 4 (DPP4)], respectively. Of note, SARS-CoV targets ciliated bronchial epithelial cells and type I and type II pneumocytes, whereas MERS-CoV infects type II pneumocytes and nonciliated bronchial cells. These differences might account for the different rates of human-to-human transmission, which was high for SARS-CoV and is moderate to low for MERS-CoV. The two viruses differ also in the duration of their epidemic, which was limited for SARS-CoV (from November 2002 to July 2003) and long-lasting for MERS-CoV, which appeared in 2012 and continues to circulate in the Middle East. As to the zoonotic reservoir, both MERS-CoV and SARS-CoV probably originated in bats (3,4) with dromedary camels serving as intermediate hosts for the human MERS-CoV infection and palm civets and raccoon dogs for SARS-CoV (5). Dromedary camels have a close association with humans in the affected areas. Of note, whereas in humans MERS-CoV infects the lower respiratory tract, rendering human-to-human transmission inefficient, in camels the virus infects the upper respiratory tract and is present in nasal secretions at high concentrations, which favors transmission to humans and other camels. However, the mechanisms of transmission from camels to humans and from humans to humans as well as the global incidence in humans are still unclear. Camels show no or mild symptoms, and antibodies found in banked sera samples show that the virus has been present in the animals for at least the past 20 y (6). In addition, most of the patients described appeared to have been infected in hospitals, Cited2 from other MERS patients, and even many of those who became infected outside a hospital report no exposure to camels. Recent epidemiological data suggest that more than 45,000 people in Saudi Arabia were seropositive for a Tepilamide fumarate MERS infection, implying that the majority of infections may not detected, the case fatality rate is lower than current estimates of about 40%, or significant levels of unreported severe disease have been misdiagnosed over the past 520 y. The trimeric S protein of MERS-CoV mediates receptor binding and membrane fusion and is the major target for neutralizing antibodies (7,8). The structure of the cellular receptor (CD26), which is conserved across many species (9), and the complex of CD26.
