Scientists at the Texas Biomedical Research Institute and the University of Chicago have discovered an unexpected strategy for the coronavirus to protect itself while multiplying in the human body, potentially leading to improved COVID-19 therapies and vaccines. 

The work, published in Nature Communications in May 2025, reveals how a minor viral protein called ORF3a acts as a security guard, protecting the virus's spike protein—which is required for entry into human cells—from destruction. 

"ORF3a is one of the most important proteins for the virus," stated Dr Chengjin Ye, lead researcher at Texas Biomed. "When we eliminate it, the virus becomes far less destructive. Now we understand why." 

The spike protein is the virus's weapon for infiltrating human cells. However, the spike protein becomes fragile during its manufacture and transportation. Here's where ORF3a comes in. 

Working with Dr Jueqi Chen of the University of Chicago, the team revealed that ORF3a contributes to the formation of "3a dense bodies" (3DBs), which are protein clusters that surround the spike like bodyguards. Before the spike reaches the virus surface, these thick bodies prevent it from breaking into smaller, non-functional fragments. 

When ORF3a is absent or inhibited, these 3DBs do not form, leaving the spike exposed and easily destroyed. This greatly reduces the virus's capacity to infect new cells. 

The discovery provides scientists with a new target for antiviral medications. If future treatments can inhibit ORF3a, they may prevent the virus from protecting itself and weaken it before it spreads. 

"This finding gives us a precise mechanism to target," said Dr Luis Martinez-Sobrido, the study's co-author. "It's not just theory—this could help guide drug and vaccine development." 

The researchers also looked at whether the protein-shielding trick is unique to the COVID-19 virus or shared by other coronaviruses. Interestingly, similar viruses in bats and pangolins produce 3DBs. However, SARS-CoV, the virus that caused the 2003 SARS outbreak, and coronaviruses in civets do not form these protective clusters. 

This could help explain the discrepancy in global impact. SARS-CoV infected around 8,000 persons worldwide (WHO statistics, 2003). In contrast, COVID-19 has affected about 770 million individuals as of 2025 (World Health Organisation). 

The lack of 3DBs in SARS-CoV might mean that its spike protein was easier to break down, which reduced its ability to spread as effectively as SARS-CoV-2. 

Now that researchers have a deeper understanding of how ORF3a functions, they want to take a step further by determining what destroys the spike protein in the absence of ORF3a protection. This could reveal new weaknesses in the virus's defence. 

They also intend to investigate how alterations in newer versions of the virus influence 3DB creation. Because the ORF3a gene is known to mutate among variations, identifying these changes could aid scientists in predicting future outbreaks. 

This discovery is the product of tight collaboration among cell biology, high-resolution imaging, and virology labs, demonstrating how integrating disciplines leads to deeper discoveries. 

"Coronaviruses have the largest genomes among RNA viruses," Dr Chen stated. "It took teamwork and advanced tools to study how these dense bodies work during infection." 

As COVID-19 evolves, research like this provides a deeper understanding of how the virus operates—and how it may be prevented. The ORF3a protein, once considered a minor component of the virus's sophisticated machinery, may now serve as a crucial target in the global fight against coronavirus.