A5044118057- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Bacteriophages and microbial interactions
- Viral Infections and Outbreaks Research
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Viral Infections and Vectors
- COVID-19 Clinical Research Studies
- Virus-based gene therapy research
- Hepatitis B Virus Studies
University of Minnesota Medical Center
2023-2024
University of Minnesota
2023-2024
The COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on injection-only delivery. Nanobodies are single-domain with therapeutic potentials. We discovered three anti-SARS-CoV-2 nanobodies, named Nanosota-2, -3, -4, from an immunized alpaca. Nanosota-2 is super potent prototypic SARS-CoV-2, Nanosota-3 highly the omicron variant, Nanosota-4 effective both...
Since the COVID-19 outbreak, raccoon dogs have been suggested as a potential intermediary in transmitting SARS-CoV-2 to humans. To understand their role pandemic and species barrier for transmission humans, we analyzed how ACE2 protein interacts with spike protein. Biochemical data showed that dog is an effective receptor protein, though not human ACE2. Structural comparisons highlighted differences virus-binding residues of compared (L24Q, Y34H, E38D, T82M, R353K), explaining varied...
A major challenge in antiviral antibody therapy is keeping up with the rapid evolution of viruses. Our research shows that nanobodies—single-domain antibodies derived from camelids—can be rapidly re-engineered to combat new viral strains through structure-guided vitro evolution. Specifically, for mutations occurring at nanobody-binding sites, we introduce randomized amino acid sequences into nanobody residues near these mutations. We then select variants effectively bind mutated target a...
Grasping the roles of epitopes in viral glycoproteins is essential for unraveling structure and function these proteins. Up to now, all identified have been found either neutralize, no effect on, or enhance entry into cells. Here, we used nanobodies (single-domain antibodies) as probes investigate a unique epitope on SARS-CoV-2 spike protein, located outside protein's receptor-binding domain. Nanobody binding this enhances cell prototypic SARS-CoV-2, while neutralizing Omicron variant....
The animal origin of SARS-CoV-2 remains elusive, lacking a plausible evolutionary narrative that may account for its emergence. Its spike protein resembles certain segments BANAL-236 and RaTG13, two bat coronaviruses considered possible progenitors SARS-CoV-2. Additionally, contains furin motif, common feature rodent coronaviruses. To explore the involvement rodents in emergence spike, we examined crystal structures receptor-binding domains (RBDs) RaTG13 each complexed with mouse receptor...
The Ebola filovirus (EBOV) poses a serious threat to global health and national security. Nanobodies, type of single-domain antibody, have demonstrated promising therapeutic potential. We identified two anti-EBOV nanobodies, Nanosota-EB1 Nanosota-EB2, which specifically target the EBOV glycoprotein (GP). Cryo-EM biochemical data revealed that binds glycan cap GP1, preventing its protease cleavage, while Nanosota-EB2 critical membrane-fusion elements in GP2, stabilizing it pre-fusion state....