Rational design of universal immunotherapy for TfR1-tropic arenaviruses

Hadas Cohen-Dvashi, Ron Amon, Krystle N. Agans, Robert W. Cross, Aliza Borenstein-Katz, Mathieu Mateo, Sylvain Baize, Vered Padler-Karavani, Thomas W. Geisbert, Ron Diskin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Certain arenaviruses that circulate in rodent populations can cause life-threatening hemorrhagic fevers when they infect humans. Due to their efficient transmission, arenaviruses pose a severe risk for outbreaks and might be exploited as biological weapons. Effective countermeasures against these viruses are highly desired. Ideally, a single remedy would be effective against many or even all the pathogenic viruses in this family. However, despite the fact that all pathogenic arenaviruses from South America utilize transferrin receptor 1 (TfR1) as a cellular receptor, their viral glycoproteins are highly diversified, impeding efforts to isolate cross-neutralizing antibodies. Here we address this problem using a rational design approach to target TfR1-tropic arenaviruses with high potency and breadth. The pan-reactive molecule is highly effective against all arenaviruses that were tested, offering a universal therapeutic approach. Our design scheme avoids the shortcomings of previous immunoadhesins and can be used to combat other zoonotic pathogens.

Original languageEnglish
Article number67
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2020


FundersFunder number
Abramson Family Center for Young Scientists
Enoch Foundation
National Institute of Allergy and Infectious DiseasesUC7AI094660
Israel Science Foundation682/16, 1775/12
Israeli Centers for Research Excellence


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