Phenotypic & functional characterization of newly evolved SARS-CoV-2 mutant viruses
Recent data have suggested that SARS-CoV-2 is becoming more contagious and transmissible due to the acquisition of several mutations in spike and other viral genes.
This NSRI IRAD project, funded in August 2021, aims to delineate the structural differences and phenotypic mutational profile of these emerging variants in both in vitro and in vivo studies using appropriate animal models. By studying structural and mutational differences, we will delineate how newly acquired mutations may provide SARS-CoV-2 with the ability to adapt to the host system and spread disease faster. This understanding can help scientists develop better therapeutic strategies to control the spread of the virus.
"New emerging viruses are always a threat to our national security mission. Therefore, understanding the pathogenicity, transmission, and mapping of SARS-CoV-2 new variants will help develop targeted therapeutics for military personnel, first responders, and the public to mitigate the disease control." — Dr. Siddappa N.Byrareddy, professor of pharmacology and experimental neuroscience at the University of Nebraska Medical Center
- Principal Investigator: Siddappa N.Byrareddy, professor of pharmacology and experimental neuroscience at the University of Nebraska Medical Center
Milestones (as of July 2022)
- Analyzed viral growth replication of SASR-CoV-2, wild type, Delta, and other variants of concern (VOCs) in various laboratory cell lines to understand the pathogenicity of different SARS-CoV-2 VOCs.
- Mapped origin, mutational profile, spreading and transmission of VOCs and Variants of Interest (VOIs), including Delta and Omicron viruses.
- Developed and tested small entry molecules against these viruses and discovered that some entry inhibitors could target SARS-CoV-2 and its VOCs can be blocked using these entry inhibitors.
- Identified host molecules that can be targeted, provided insights into molecular mechanisms contributing to SARS-CoV-2 pathogenesis, and developed a new strategy to block SARS-CoV-2 infection.
- Using a combination of viral drugs with inhibitors of the mTOR signaling pathways has emerged as one of the promising approaches to treat SARS-CoV-2 infections.
Are we moving toward ending SARS-CoV-2?
Journal of Medical Virology | July 2022
Binding of the SARS-CoV-2 envelope E protein to human BRD4 is essential for infection
Structure | June 2022
Combining antiviral drugs with BET inhibitors is beneficial in combatting SARS-CoV-2 infection
Clinical and Translational Discovery | May 2022
Complex Mutation Pattern of Omicron BA.2: Evading Antibodies without Losing Receptor Interactions
International Journal of Molecular Sciences | May 2022
PI3K-α/mTOR/BRD4 inhibitor alone or in combination with other anti-virals blocks replication of SARS-CoV-2 and its variants of concern, including Delta and Omicron
Clinical and Translational Medicine | April 2022
Omicron SARS-CoV-2 variant: Unique features and their impact on pre-existing antibodies
Journal of Autoimmunity | January 2022
Discovery and Evaluation of Entry Inhibitors for SARS-CoV-2 and Its Emerging Variants
Journal of Virology| November 2021
Evolutionary analysis of the Delta and Delta Plus variants of the SARS-CoV-2 viruses
Journal of Autoimmunity | November 2021
The team will now complete in vivo replication of SARS-CoV-2 and its variants in animal models and comparative analysis to identify which virus is more or less pathogenic in vivo and tissue compartmentalization.