Structural Basis of MERS‐CoV Receptor Interactions and Antibody Neutralisations

ABSTRACT 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.