title: Rapid screening for entry inhibitors of highly pathogenic viruses under low-level biocontainment.
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.
authors.affiliation: Department of Pediatrics, Weill Medical College, Cornell University, New York, New York, United States of America.
authors.forename: Aparna
authors.initials: A
authors.lastname: Talekar
authors.forename: Antonello
authors.initials: A
authors.lastname: Pessi
authors.forename: Fraser
authors.initials: F
authors.lastname: Glickman
authors.forename: Uttara
authors.initials: U
authors.lastname: Sengupta
authors.forename: Thomas
authors.initials: T
authors.lastname: Briese
authors.forename: Michael A
authors.initials: MA
authors.lastname: Whitt
authors.forename: Cyrille
authors.initials: C
authors.lastname: Mathieu
authors.forename: Branka
authors.initials: B
authors.lastname: Horvat
authors.forename: Anne
authors.initials: A
authors.lastname: Moscona
authors.forename: Matteo
authors.initials: M
authors.lastname: Porotto
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000737:chemistry; D000998:Antiviral Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D019295:Computational Biology / Q000379:methods*; D018076:DNA, Complementary / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D057809:HEK293 Cells; D045404:Hendra Virus / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D045405:Nipah Virus / Q000378:metabolism*; D051381:Rats; D013678:Technology, Pharmaceutical / Q000379:methods; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D018076:DNA, Complementary