MERS: from Middle East to the East and beyond

Abstract

Since its first appearance in 2012, MERS has affected >25 countries in four continents with >2,000 cases and a high fatality rate of >30%. A novel lineage C betacoronavirus, MERS coronavirus (MERS-CoV), has been confirmed to be the etiological agent. Human dipeptidyl peptidase 4 was found to be the cellular receptor for MERS-CoV. Subsequent detection of MERS-CoV and its antibodies in dromedaries in various countries in the Middle East and North Africa have implied that these animals are probably the reservoir for MERS-CoV. Other lineage C betacoronaviruses in bats (e.g. Tylonycteris bat CoV HKU4, Pipistrellus bat CoV HKU5) and hedgehogs were found to be closely related to MERS-CoV. So far, detection of MERS-CoV and discoveries of its closely related CoVs are most efficiently achieved through RT-PCR. Although RT-PCR is highly sensitive, its turn-around-time is about four hours and the test requires expensive equipment, stringent laboratory set-up and personal attention to prevent laboratory PCR product cross contamination which may lead to false-positive results. Recently, we have developed a monoclonal antibody-based rapid nucleocapsid protein detection assay for on-site diagnosis of MERS-CoV, which can be finished in 30 minutes. In addition to human and camel samples, we examined the usefulness of this rapid assay to detect other lineage C betacoronaviruses closely related to MERS-CoV in bats. The rapid MERS-CoV nucleocapsid protein detection assay was tested positive in 24 (88.9%) of 27 Tylonycteris bat CoV HKU4 RNA-positive alimentary samples of Tylonycteris pachypus and 4 (19.0%) of 21 Pipistrellus bat CoV HKU5 RNA-positive alimentary samples of Pipistrellus abramus. The rapid assay was tested negative in all 51 alimentary samples RNA-positive for alphacoronaviruses (Rhinolophus bat CoV HKU2, Myotis bat CoV HKU6, Miniopterus bat CoV HKU8 and Hipposideros batCoV HKU10) and 32 alimentary samples positive for lineage B (SARS-related Rhinolophus bat CoV HKU3) and lineage D (Rousettus bat CoV HKU9) betacoronaviruses. This rapid assay will facilitate rapid on-site diagnosis of MERS and rapid on-site screening of animal samples for ancestors of MERS-CoV and tracking transmission in the related bat species from the Middle East to the East and beyond.