J Med Chem. 2021 Feb 1
Yingjun Li, Liu Cao, Ge Li, Feng Cong, Yunfeng Li, Jing Sun, Yinzhu Luo, Guijiang Chen, Guanguan Li, Ping Wang, Fan Xing, Yanxi Ji, Jincun Zhao, Yu Zhang, Deyin Guo, and Xumu Zhang
Products used in the paper Details Operation
Adenoassociated virus 9 encoding hACE2 Adenoassociated virus 9 encoding hACE2 was purchased from Packgene (AAV-hACE2) Request Quote

Research Field: Covid-related

AAV Serotype: AAV9

Dose: The modified intratracheal aerosolization was used to intratracheally deliver AAV vector (5 × 10^11 GC) to lung tissue of four-week-old BALB/c mice

Routes of Administration: The modified intratracheal aerosolization was used to intratracheally deliver AAV vector (5 × 10^11 GC) to lung tissue of four-week-old BALB/c mice

Targeted organ: lung

Animal or cell line strain: BALB/c mice

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in a global pandemic due to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the time of this manuscript’s publication, remdesivir is the only COVID-19 treatment approved by the United States Food and Drug Administration. However, its effectiveness is still under question due to the results of the large Solidarity Trial conducted by the World Health Organization. Herein, we report that the parent nucleoside of remdesivir, GS-441524, potently inhibits the replication of SARS-CoV-2 in Vero E6 and other cell lines. Challenge studies in both an AAV-hACE2 mouse model of SARS-CoV-2 and in mice infected with murine hepatitis virus, a closely related coronavirus, showed that GS-441524 was highly efficacious in reducing the viral titers in CoV-infected organs without notable toxicity. Our results support that GS-441524 is a promising and inexpensive drug candidate for treating of COVID-19 and other CoV diseases.

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