Structural Basis of MERS-CoV Receptor Interactions and Antibody Neutralisations

Increasing outbreaks of coronaviruses underscore the importance of antivirals and vaccines that can combat a wide range of coronaviruses. Neutralising antibodies (nAbs), along with vaccines and small-molecule drugs, are among the most promising treatments and prevention options against coronaviruses. Here, we focus on Middle East Respiratory Syndrome coronavirus (MERS-CoV) and discuss receptor usage and current progress in antibody research against MERS-CoV infections. First detected in Saudi Arabia and Jordan in 2012, MERS-CoV is a lethal zoonotic pathogen. MERS-CoV infections have been reported by 27 countries between April 2012 till now, with 953 deaths (∼35% mortality) (5 new infections and 4 fatalities reported as of 1 October 2024). WHO identified MERS-CoV as a high-threat pathogen due to its severity, high mortality rate, and potential for epidemic or pandemic spread with recent outbreaks and deaths raising more concerns amidst the COVID-19 pandemic. As of now, there is no antiviral drugs or vaccine against MERS-CoV available. Here we provide a perspective on receptor usage, the risk of MERS-CoV and other CoVs evolution on future pandemics, and the mechanisms of MERS-CoV-derived nAbs. We offer insight into how these antibodies cross-react and cross-neutralise by analysing available structures of spike glycoprotein-antibody complexes. This review provides an update and a basis for the development of antibodies and vaccines for MERS-CoV, and possibly for the designing of next-generation pan-coronavirus vaccines and antivirals.