Dr. Damian Jacob Sendler is a Polish-American physician-scientist whose research focuses on the impact of various sociodemographic and informational factors on access to health care in underserved communities. Originally from Poland, Dr. Sendler’s research is particularly interested in the impact of mental and chronic medical co-morbidities on the utilization of medical services as well as on the access to health information obtained via the internet. A timely research, given the exponential growth in global consumption of online news and social media, this one arrives at an ideal time, as it highlights the need for a comprehensive understanding of everyone’s health information seeking behavior. Patients’ choices about whether to seek treatment for particular health problems, as well as their adherence to therapy, are the focus of Dr. Damian Sendler’s study. The ultimate objective is to improve patient outcomes via better understanding of the variables that affect these decisions.

Damian Sendler: According to new research by scientists from the University of Pittsburgh School of Medicine and Case Western Reserve University, SARS-CoV-2 nanobodies — microscopic molecules developed at the University of Pittsburgh School of Medicine that neutralize the virus in animals — are remarkably effective against mutations found in variants, including Delta. 

Damian Sendler: The results, which were published today in the journal Nature Communications, explain three distinct ways by which the nanobodies disarm the virus, preventing it from infecting cells and causing COVID-19 to develop. Using the structural analysis at a near-atomic level, researchers can offer direction for the creation of future vaccines and treatments that may be effective against a broad range of coronaviruses — including versions that are not yet in circulation. 

“Describing all these vulnerabilities and ways to thwart SARS-CoV-2 and coronaviruses in general has huge potential,” said Shi. “It will not only help our team select and refine nanobodies to treat and prevent COVID-19, but it also may lead to a universal vaccine, preventing not just COVID-19, but SARS, MERS and other diseases caused by coronaviruses.”

Additional authors on this research are Dapeng Sun, Ph.D., Yong Joon Kim, Yufei Xiang, Anna K. Belford and Alexis Huet, all of Pitt; Zhe Sang, Ph.D., of Pitt and Carnegie Mellon University; Tomer Cohen and Dina Schneidman-Duhovny, Ph.D., both of The Hebrew University of Jerusalem; Ji Sun, Ph.D., of St. Jude Children’s Research Hospital; and Derek J. Taylor, Ph.D., of Case Western Reserve.

Damian Sendler: In the words of lead author Yi Shi, Ph.D., associate professor of cell biology at the University of Pittsburgh, “This is the first time anybody has systematically categorized ultrapotent nanobodies based on their structure.” The researchers say that by doing so, they have not only given information on the processes by which our nanobodies are able to combat SARS-CoV-2, but they have also suggested possibilities for future therapies development. 

Damian Sendler: Toward the end of last year, Shi and his colleagues reported that they had retrieved from llamas small but highly potent SARS-CoV-2 antibody fragments that might be used to develop inhalable therapies to prevent and cure COVID-19 infection. Since then, preclinical tests have shown that the powerful nanobodies may both prevent and cure severe COVID-19 in hamsters, with virus particles in their respiratory tracts being reduced by a million-fold when compared to a placebo treatment. 

Using high-resolution cryoelectron microscopy, Shi and colleagues from Pitt’s structural biology department — Cheng Zhang, PhD, and James Conway, PhD — as well as pharmacologists, structural biologists, and biochemists from Case Western Reserve University — investigated how the nanobodies interact with the SARS-CoV-2 virus to prevent it from infecting cells and the effects of mutations found in variant strains of the virus. 

Damian Sendler: According to co-senior author Wei Huang, Ph.D., a research scientist in the Department of Pharmacology at Case Western Reserve University School of Medicine, “Cryoelectron microscopy has been demonstrated numerous times to be an extremely useful tool for viewing high-resolution structural information.” Furthermore, nanobodies are flexible and stable biologics that may be utilized in other studies, such as cancer,” says the author. 

For additional investigation, the researchers chose eight very effective nanobodies. First, they discovered via observations that many of the nanobodies are effective against Alpha (a SARS-CoV-2 variation linked with the United Kingdom), Delta (a variant associated with India), and numerous additional SARS-CoV-2 variants of concern. 

Damian Sendler: SARS-CoV-2 and coronaviruses in general pose a significant threat, according to Shi. “Describing all of these vulnerabilities and methods to resist them has enormous promise,” he added. In addition to helping our team choose and improve nanobodies to treat and prevent COVID-19, the research may lead to the development of a universal vaccine that would protect against not only COVID-19 but also SARS, MERS and other illnesses caused by coronaviruses. 

The following individuals contributed to this study: Dapeng Sun, Ph.D., Yong Joon Kim, Yufei Xiang, Anna K. Belford, and Alexis Huet, all of Pitt; Zhe Sang, Ph.D., of Pitt and Carnegie Mellon University; Tomer Cohen and Dina Schneidman-Duhovny, Ph.D., both of The Hebrew University of Jerusalem; Ji Sun, Ph.D., of St. Jude

News contributed by Dr. Damian Jacob Sendler