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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
Rapid screening for entry inhibitors of highly pathogenic viruses under low-level biocontainment
Aparna Talekar1, Antonello Pessi, Fraser Glickman
1Department of Pediatrics, Weill Medical College, Cornell University, New York, New York, United States of America.
Abstract:
Emerging viruses including Nipah, Hendra, Lujo, and Junin viruses have enormous potential to spread rapidly. Nipah virus, after emerging as a zoonosis, has also evolved the capacity for human-to-human transmission. Most of the diseases caused by these pathogens are untreatable and require high biocontainment conditions. Universal methods for rapidly identifying and screening candidate antivirals are urgently needed. We have developed a modular antiviral platform strategy that relies on simple bioinformatic and genetic information about each pathogen. Central to this platform is the use of envelope glycoprotein cDNAs to establish multi-cycle replication systems under BSL2 conditions for viral pathogens that normally require BSL3 and BSL4 facilities. We generated monoclonal antibodies against Nipah G by cDNA immunization in rats, and we showed that these antibodies neutralize both Nipah and Hendra live viruses. We then used these effective Henipavirus inhibitors to validate our screening strategy. Our proposed strategy should contribute to the response capability for emerging infectious diseases, providing a way to initiate antiviral development immediately upon identifying novel viruses.
Insights
A new antiviral platform enables rapid screening of potential drugs for emerging viruses like Nipah and Hendra. This strategy uses glycoprotein cDNAs for safer, faster development of treatments against dangerous, untreatable infectious diseases.
Area of Science:
- Virology
- Infectious Diseases
- Drug Discovery
Background:
- Emerging viruses like Nipah and Hendra pose significant global health threats due to rapid spread and untreatable diseases.
- High biocontainment (BSL3/BSL4) is typically required for studying these dangerous pathogens, hindering antiviral development.
Purpose of the Study:
- To develop a universal, modular antiviral platform for rapid identification and screening of candidate antivirals against emerging viruses.
- To enable the study and development of antivirals for high-risk pathogens under lower biocontainment (BSL2) conditions.
Main Methods:
- Utilized envelope glycoprotein cDNAs to create multi-cycle replication systems for pathogens requiring high biocontainment.
- Generated monoclonal antibodies against Nipah virus glycoprotein (G) via cDNA immunization in rats.
- Validated the screening strategy using validated Henipavirus inhibitors.
Main Results:
- Established a BSL2-compatible platform for studying viruses that normally require BSL3/BSL4 facilities.
- Monoclonal antibodies against Nipah G demonstrated neutralization of both Nipah and Hendra live viruses.
- Successfully validated the proposed antiviral screening strategy.
Conclusions:
- The developed modular antiviral platform strategy facilitates rapid antiviral development for emerging infectious diseases.
- This approach allows for immediate initiation of antiviral research upon identification of novel viruses.
- The strategy enhances global response capabilities for emerging viral threats.
