Human organs-on-chips as tools for repurposing approved drugs as potential influenza and COVID19 therapeutics in viral pandemics

Longlong Si; Haiqing Bai; Melissa Rodas; Wuji Cao; Crystal Yur Oh; Amanda Jiang; Atiq Nurani; Danni Y Zhu; Girija Goyal; Sarah Gilpin; Rachelle Prantil-Baun; Donald E. Ingber

conditions. However, in contrast to the results we obtained testing drugs with pseudotyped virus, and the other groups observed with native SARS-CoV-2, we found that only two of these drugs -amodiaquine and toremifene -prevented infection by Amodiaquine is an anti-malarial drug related to chloroquine and hydroxychloroquine 42 . This drug decreased the entry of SARS-CoV-2pp into human airway cells at 1.24 µM by ~60%, which can be clinically achievable as demonstrated in the plasma of patients with malaria who received 300 mg administration 43 . Toremifene, is a selective estrogen receptor modulator, which is also currently under clinical development for the treatment of Ebola virus infection 25, 26 . While both of these drugs have been approved in the past by the FDA for other applications (treatment of malaria for amodiaquine and metastatic breast carcinoma for toremifene), each has its own distinct therapeutic and toxicity profile that makes it more or less attractive as a potential drug treatment for COVID19. Amodiaquine, which was widely used in the past for both prophylaxis and treatment of malaria, was withdrawn from prophylactic use due to rare occurrence of agranulocytosis and hepatitis 44 , and is now only used as a second line acute treatment of P. falciparum-resistant malaria in Africa in combination with author/funder. All rights reserved. No reuse allowed without permission.