New research has identified key mutations in the Middle East respiratory syndrome coronavirus (MERS-CoV) that may influence how easily the virus infects cells and evades immune responses, offering important insights for pandemic preparedness.

The study, supported by funding from The Pandemic Institute and led by researchers at the University of Liverpool plus colleagues from across the world, focused on changes in the virus’s “Spike” protein – the part of the virus that allows it to enter human cells. Understanding how this protein evolves is critical, as it is also the main target of immune responses and future vaccines.

MERS-CoV first emerged in 2012 and continues to cause sporadic outbreaks, mainly in the Middle East. While it does not spread as easily as some other respiratory viruses, it has a high mortality rate and is considered a potential pandemic threat if it acquires more efficient human-to-human transmission.

Tracking viral evolution

In this study, researchers analysed 584 genetic sequences of MERS-CoV collected from human infections between 2012 and 2024. From these, they identified 15 naturally occurring mutations in the Spike protein that were likely to affect how the virus behaves. These mutations were then recreated in the laboratory using a safe “pseudovirus” system, allowing scientists to test how each change altered the virus’s ability to fuse with cells and resist antibodies. 

The team, led by Professor Julian Hiscox, found that three mutations, known as I529T, E536K and L745F, enhanced the virus’s ability to fuse with human cells. This process, known as membrane fusion, is a key step in infection. When fusion is more efficient, viruses can spread more easily between cells, potentially increasing transmissibility. Laboratory imaging showed that these mutations also led to greater formation of “syncytia”, clusters of fused cells that are often associated with more severe infection.

Evading immune response

Equally important were findings related to immune escape. Five mutations, L411F, T424I, L506F, L745F and T746K, reduced how effectively antibodies from recovered patients could neutralise the virus.

This suggests that some naturally occurring mutations may allow MERS-CoV to partially evade immunity gained from previous infection. A key concern is that as the virus evolves, it may become less recognisable to the immune system, which could make reinfections more likely or reduce the effectiveness of future vaccines.

Notably, one mutation (L745F) appeared to do both, increasing cell fusion while also reducing antibody neutralisation, highlighting how certain changes could make the virus both more infectious and harder to control.

Implications for public health

Although MERS-CoV currently causes limited outbreaks, the study highlights why continued surveillance is essential. The virus still circulates in camel populations with the ability to spill over into humans, and each infection provides an opportunity for further evolution. Recent cases reported internationally underline the ongoing risk. While large-scale transmission remains rare, the possibility of the virus adapting to spread more efficiently cannot be ruled out.

This research also demonstrates the value of laboratory tools that can rapidly assess new mutations as they appear. The pseudotyping system developed in the study allows scientists to test emerging variants quickly without handling the live virus.

Preparing for future pandemics

The findings will help inform the development of vaccines, antiviral treatments and antibody therapies by identifying which parts of the virus are most likely to change.

Crucially, the work reflects The Pandemic Institute’s mission to strengthen global readiness for emerging infectious diseases by connecting scientific discovery with real-world impact.

Read the full paper here: Characterisation of Naturally Occurring MERS-CoV Spike Mutations and Their Impact on Fusion and Neutralisation