Author: Laura Riva; Shuofeng Yuan; Xin Yin; Laura Martin-Sancho; Naoko Matsunaga; Sebastian Burgstaller-Muehlbacher; Lars Pache; Paul P. De Jesus; Mitchell V. Hull; Max Chang; Jasper Fuk-Woo Chan; Jianli Cao; Vincent Kwok-Man Poon; Kristina Herbert; Tu-Trinh Nguyen; Yuan Pu; Courtney Nguyen; Andrey Rubanov; Luis Martinez-Sobrido; Wen-Chun Liu; Lisa Miorin; Kris M. White; Jeffrey R. Johnson; Christopher Benner; Ren Sun; Peter G. Schultz; Andrew Su; Adolfo Garcia-Sastre; Arnab K. Chatterjee; Kwok-Yung Yuen; Sumit K. Chanda
Title: A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals Document date: 2020_4_17
ID: 1fgnfh62_62
Snippet: MLN-3897 (AVE-9897) is an orally active chemokine CCR1 antagonist and was evaluated in phase II clinical studies for the treatment of rheumatoid arthritis (RA) and multiple sclerosis (MS) 72 , showing a dose of 10 mg once daily was well tolerated 73 . It was determined to inhibit SARS-CoV-2 replication at an estimated EC 50 concentration of 140 nM (Figure 2) , and the C max of the compound has been reported at 9.0 nM (10 mg QD). Therefore, additi.....
Document: MLN-3897 (AVE-9897) is an orally active chemokine CCR1 antagonist and was evaluated in phase II clinical studies for the treatment of rheumatoid arthritis (RA) and multiple sclerosis (MS) 72 , showing a dose of 10 mg once daily was well tolerated 73 . It was determined to inhibit SARS-CoV-2 replication at an estimated EC 50 concentration of 140 nM (Figure 2) , and the C max of the compound has been reported at 9.0 nM (10 mg QD). Therefore, additional in vivo studies will be required to determine if sufficient systemic concentrations can be reached to promote antiviral activities. The mechanism by which CCR1 antagonism inhibits SARS-CoV-2 infection requires further investigation. However, it has been reported that CCR1 inhibition with MLN-3897 potentially blocks ERK phosphorylation, leading to suppression of the mitogen-activated protein kinase (Raf/MEK/ERK) signal transduction pathway 74 . Interestingly, Raf/MEK/ERK signaling pathways are employed by SARS-CoV-1 to support its replication via multiple well-documented mechanisms 75, 76 , and thus this signaling axis may also represent a critical therapeutic target for host-directed SARS-CoV-2 antivirals.
Search related documents:
Co phrase search for related documents- antiviral activity and ERK phosphorylation: 1, 2, 3, 4
- antiviral activity and host direct: 1, 2, 3, 4, 5, 6, 7
- antiviral activity and investigation require: 1
- antiviral activity and mitogen activate: 1
- antiviral activity and multiple sclerosis: 1, 2, 3, 4, 5, 6, 7, 8
- clinical study and host direct: 1, 2
- clinical study and investigation require: 1, 2
- clinical study and multiple sclerosis: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20
- host direct and multiple sclerosis: 1
Co phrase search for related documents, hyperlinks ordered by date