Scientists uncover how COVID-19 variants outsmart the immune system

Researchers at the Icahn School of Medicine and collaborators provide a roadmap for designing next-generation antibodies that might keep pace with viral evolution

The Mount Sinai Hospital / Mount Sinai School of Medicine

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Above: Cartoon model of the SARS-CoV-2 spike protein showing the different regions (or domains) that are associated with known viral mutations and antibodies can recognize and attach to. These include areas involved in binding to human cells and in helping the virus fuse with them.

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Credit: Image credit: Feng, et al., Cell Systems.

New York, NY [November 21, 2025]—Researchers at the Icahn School of Medicine at Mount Sinai and collaborators have created the most comprehensive map to date showing how antibodies attach to the SARS-CoV-2 virus, which causes COVID-19, and how viral mutations weaken that attachment. The findings, published in the November 21 online issue of Cell Systems, a Cell Press journal, explain why variants like Omicron can evade immune defenses and suggest new strategies for building longer-lasting antibody therapies and vaccines.

The team analyzed more than a thousand three-dimensional structures of antibodies bound to the virus’s spike protein, the main target for immune recognition, and compiled them into a structural atlas of COVID-19 antibodies. By studying these structures together for the first time, the researchers revealed a detailed picture of how the immune system targets the virus and how the virus evolves to evade it.

“Scientists around the world have solved thousands of individual antibody-virus structures, but until now, no one had looked at them together,” says senior author Yi Shi, PhD, Associate Professor of Pharmacological Sciences, and Director of the Center for Protein Engineering and Therapeutics, at the Icahn School of Medicine. “By uniting all these data, we were able to see the bigger picture—how fully antibodies cover the virus’s surface and how mutations in newer variants like Omicron can undermine that protection. It gives us a clearer view of both the strengths and limits of our immune system.”

The researchers found that antibodies, including many used in clinical treatments, recognize nearly every exposed region of the spike protein’s receptor-binding domain, a critical region of the virus. Despite this broad coverage, mutations in newer variants have weakened the binding of almost all antibodies to some degree. Many antibodies, though different in sequence, bind to the virus in strikingly similar ways, suggesting that there are only a few effective structural ways to neutralize it. That convergence, say the investigators, helps explain why the virus can mutate around immunity so efficiently.

The study also highlights the potential of nanobodies—tiny, highly stable antibody fragments that can reach parts of the virus that standard antibodies often miss. Because they can recognize deeply buried regions of the spike protein that tend to remain unchanged as the virus evolves, nanobodies could serve as powerful starting points for developing next-generation antiviral drugs.

“Our findings highlight the limits of the antibodies we currently rely on,” Dr. Shi says. “While these antibodies have been remarkably effective, the virus keeps finding ways to escape them.”

“To stay ahead, we’ll need to design next-generation antibodies that can recognize and latch onto multiple regions of the virus at once, making it much harder for the virus to evade our defenses as it continues to evolve,” adds Frank (Zirui) Feng, the study’s first author and a master’s student in the Biomedical Data Science and AI program at Mount Sinai.

Although the study focused on one key part of the spike—the receptor-binding domain—the researchers note that similar patterns of immune escape are likely occurring elsewhere in the virus. They emphasize that the results do not mean the immune system or vaccines no longer work. Vaccination and natural immunity still provide vital protection through a wide range of immune responses, even when certain antibodies lose potency.

Next, the team plans to apply this large-scale structural approach to other viruses to uncover shared principles of antibody recognition. Ultimately, they hope these insights will guide the development of durable antibody treatments capable of withstanding viral evolution and improving preparedness for future pandemics.

“The immune system is remarkably adaptable, but the virus is clever,” says co-author Adolfo Garcia-Sastre, PhD, Irene and Dr. Arthur M. Fishberg Professor of Medicine, and Director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine. “By analyzing how antibodies attach to the virus and where they fall short, we gain a detailed map of the virus’s vulnerabilities. This insight not only helps us understand why some antibodies stop working as the virus evolves but also guides the design of next-generation therapies that can stay one step ahead, potentially improving how we prevent and treat COVID-19 and other viral infections.”

As a part of this research, the team has created an open-access data set and interactive web tool that allows scientists to explore antibody structures in detail, providing a powerful resource to collectively accelerate research on COVID-19 and other viruses.

The paper is titled “One Thousand SARS-CoV-2 Antibody Structures Reveal Convergent Binding and Near-Universal Immune Escape.”

The study’s authors, as listed in the journal, are Zirui Feng, Zhe Sang, Yufei Xiang, Alba Escalera, Adi Weshler, Dina Schneidman- Duhovny, Adolfo García-Sastre, and Yi Shi.

This work is supported by National Institutes of Health grant R01 AI163011. This work is also partly supported by the Center for Research on Influenza Pathogenesis and Transmission, an National Institute of Allergy and Infectious Diseases (NIAID) Center of Excellence for Influenza Research and Response (contract # 75N93021C00014), and by NIAID grant U19AI135972. Research reported in this publication was supported by NIAID Award G20AI174733. See the Cell Systems paper for details on conflicts of interest.

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About the Icahn School of Medicine at Mount Sinai

The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City’s large and diverse patient population.  

The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master’s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. Its Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 560 postdoctoral research fellows. 

Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges.  More than 4,500 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.

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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai

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Journal

Cell Systems

Subject of Research

Not applicable

Article Title

One Thousand SARS-CoV-2 Antibody Structures Reveal Convergent Binding and Near-Universal Immune Escape

Article Publication Date

21-Nov-2025

 

Study shows some holiday gifts can backfire – leading to hurt feelings, bad reviews

Florida International University

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New research from FIU Business shows that well-intended presents like weight-loss teas or gym memberships can unintentionally send the wrong message – and ultimately trigger negative online reviews that hurt brands.

Published in the Journal of Retailing, the study by Linnéa Chapman, assistant professor of marketing and logistics at FIU, and Farnoush Reshadi of Worcester Polytechnic Institute finds that self-improvement gifts often make recipients feel judged rather than appreciated. That emotional sting frequently spills over into consumer behavior.

“The intention may be positive, but these gifts can imply that you’re not good enough as you are,” Chapman said. “That can sting, and people take out their hurt feelings on the products, for example by giving them low star ratings.”

In five experiments involving a total of 1,340 participants, Chapman compared reactions to self-improvement products versus neutral versions of the products. In one test, participants were gifted a “Get Lean” weight-loss tea instead of Moroccan tea. In another, the gift was a “Communications Skills” calendar rather than a trivia-based “Did You Know?” calendar.

Across every scenario, people who received the self-improvement gift rated it lower, spoke less positively about it, or were more likely to endorse negative online reviews. When they purchased those same products for themselves, however, the effect vanished.

The research identified “hurt feelings” as the emotional trigger driving negative word of mouth.

“Gifts are supposed to signal love and generosity,” Chapman said. “But a self-improvement gift can threaten someone’s view of themselves as lovable and acceptable as they are. It challenges a very basic social need – to be valued without conditions.”

 

Chapman’s research suggests that many recipients redirect their frustration toward the product and the brand, using online reviews as a socially acceptable outlet for disappointment.

The study carries a clear warning for retailers ahead of the upcoming gift-giving season. Self-improvement goods represent a $43 million global market that is expected to reach $67 billion by 2030 – but pushing them as holiday gifts may backfire.

“A yoga mat in January says, ‘I’m motivated,’” Chapman said. “A yoga mat under the Christmas tree might say, ‘You need to lose weight.’ When it comes to self-improvement products, it’s better to stick to buying them for yourself.”

In an era where one-star reviews can deter hundreds of potential customers, understanding the psychology of gift giving can help retailers avoid costly reputational hits, the researchers said.

They recommend that companies rethink timing and framing of their marketing:

• Shift promotions for self-improvement items like fitness equipment or self-help books from November and December to January, when consumers are focused on their own New Year’s resolutions.
• Rethink pricing incentives during gifting seasons. If retailers discount both self-improvement and leisure products for the holidays, Chapman suggests spotlighting the latter instead.
• Humanize review requests. When companies solicit feedback, adding a personal touch such as a note signed by a real employee (“Thanks for your review! – Alex, Founder”) can reduce consumers’ negativity.
• Offer small incentives for reviews. Even a modest gift card can increase positivity and reduce the likelihood of low ratings.

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Journal

Journal of Retailing

DOI

10.1016/j.jretai.2025.04.005 

Method of Research

Survey

Subject of Research

People

Article Title

Generating insult from injury: Receiving self improvement gifts causes negative word of mouth

 

A mulching film that protects plants without pesticides or plastics

“Citronella Oil Incorporated into Active Mulching Films for Insect Control in Strawberry Crop”

American Chemical Society

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A new biodegradable alternative to traditional plastic films protected strawberry plants by naturally repelling pests with citronella oil.

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Credit: Camila Gil

Whether you’re a home gardener or an industrial farmer, you might be familiar with mulching films — plastic sheets laid over the soil to protect seedlings and promote crop growth. But like many other plastic materials, these films can release damaging microplastics and don’t have any insect-repelling power. So, a team reporting in ACS Agricultural Science & Technology has developed an alternative biodegradable mulching film that also naturally repels pests using citronella oil.

“This research shows that it is possible to protect crops using biodegradable materials that reduce both pesticide use and plastic pollution. Our goal is to bring farmers closer to safer and more sustainable agricultural practices,” explains Camila Gil, the corresponding author of the study.

Mulching films retain moisture in the soil and prevent weed growth, but they’re often made from polyethylene plastic. As a result, the films are hard to recycle and can release microplastics that negatively impact soil organisms. Now, scientists are developing biodegradable mulching films using plant-based polymers such as cellulose acetate. Gil and colleagues wanted to improve a cellulose acetate film by including the insect repellant citronella oil. So, the team created a robust, citronella oil-infused film and investigated how well that film protected strawberry plants from a common pest: the silverleaf whitefly (Bemisia tabaci).

The researchers created films with varying concentrations of citronella oil and found that the oil did not reduce the film’s strength or flexibility. However, the new film did not retain moisture as well as traditional plastic film. To simulate a realistic use case, researchers covered the soil of strawberry plants with one of the different films and wrapped the setups in insect-capturing nets. Then they released around 25 whiteflies inside the nets. This setup was repeated on an unprotected control plant and on a plant protected with polyethylene film. The team found that after seven days, pests laid around six eggs on plants protected with the citronella-oil-containing films, far fewer than the 30-plus eggs laid on plants with traditional plastic film or no soil protection at all. The researchers say that this work represents a step toward a more environmentally friendly way to protect crops without using plastics or environmentally damaging pesticides.

The authors acknowledge funding from the Conselho Nacional de Desenvolvimento Cientifíco e Tecnológico (National Council for Scientific and Technological Development), the Fundação de Amparo à Pesquisa de Minas Gerais (Research Support Foundation of the State of Minas Gerais), and the Coordenação de Aperfeiçoamento de Pessoal de Niv́el Superior (Brazilian Federal Agency for Support and Evaluation of Graduate Education).

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The American Chemical Society (ACS) is a nonprofit organization founded in 1876 and chartered by the U.S. Congress. ACS is committed to improving all lives through the transforming power of chemistry. Its mission is to advance scientific knowledge, empower a global community and champion scientific integrity, and its vision is a world built on science. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, e-books and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

Registered journalists can subscribe to the ACS journalist news portal on EurekAlert! to access embargoed and public science press releases. For media inquiries, contact newsroom@acs.org.

Note: ACS does not conduct research but publishes and publicizes peer-reviewed scientific studies.

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Journal

ACS Agricultural Science & Technology

DOI

10.1021/acsagscitech.5c00451 

Article Title

“Citronella Oil Incorporated into Active Mulching Films for Insect Control in Strawberry Crop”

 

Home buyers are overpaying mortgage fees. Shopping around can help.

University of Florida

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A new study reveals that most U.S. home buyers are overpaying mortgage fees, a market totaling more than $13 billion a year.

The report also finds that searching for lower costs can save consumers an average of $32 in fees and more than $1,000 in interest per loan, making competitive pricing a consumer’s best defense against overpayment.

“If they have a chance, lenders will definitely make borrowers pay higher fees,” said Cheng “Cathy” Zhang, Ph.D., a postdoctoral associate in the University of Florida’s Warrington College of business and author of the study. “To reduce that overpayment, there are things home buyers can do: shopping, using brokers or using simplified loans, like zero-fee loans.”

Of all those fee-busting options, shopping around saved the most, in both fees and interest rates, Zhang found. With many lenders offering instant quotes online, shopping may not even take that long. 

But consumers routinely report that they’re unaware that mortgage fees and total costs vary a lot by lenders, leaving them vulnerable to paying more than they need to.
“It’s just because they don’t know. Just one small step might be able to save them a lot,” Zhang said.

While researchers have previously looked at the market for mortgage rates, lenders did not have to report other costs, like origination fees, until recently. Starting in 2018, the Consumer Financial Protection Bureau started collecting and sharing data on the total costs of mortgages, including these fees. 

In her study, Zhang found that the fees average around 1-3% of the mortgage, or a little over $1,000 on an average loan of about $269,000. Some fees can approach 8% of the loan, however. On the other hand, some lenders will roll the fees into the interest rates borrowers pay over time. These types of loans, known as simplified or zero-fee loans, can actually save borrowers on overall costs, Zhang found.

Not everyone is overpaying, though. Savvy home buyers, those who’ve purchased homes in the past or people with higher incomes are more likely to end up paying less.
“Overall, people are overpaying for mortgage fees,” Zhang said. “But it’s largely driven by less sophisticated borrowers. For example, lower income borrowers, or those with less education.”

The study was published Oct. 31 in the Journal of Real Estate Finance and Economics.

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Journal

The Journal of Real Estate Finance and Economics

DOI

10.1007/s11146-025-10039-2 

Method of Research

Data/statistical analysis

Subject of Research

Not applicable

Article Title

Do U.S. Borrowers Overpay Mortgage Fees?