Published Anti-SARS-CoV-2 In Vitro Hits Share Common Mechanisms of Action that Synergize with Antivirals.
Published Anti-SARS-CoV-2 In Vitro Hits Share Common Mechanisms of Action that Synergize with Antivirals.
复制标题
已发表的抗 SARS-CoV-2 体外热门药物具有与抗病毒药物协同作用的共同作用机制。
DOI：
10.1101/2021.03.04.433931
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Chen,Bin
中科院分区：
文献类型：
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作者：
Xing,Jing;Paithankar,Shreya;Liu,Ke;Uhl,Katie;Li,Xiaopeng;Ko,Meehyun;Kim,Seungtaek;Haskins,Jeremy;Chen,Bin
The global efforts in the past year have led to the discovery of nearly 200 drug repurposing candidates for COVID-19. Gaining more insights into their mechanisms of action could facilitate a better understanding of infection and the development of therapeutics. Leveraging large-scale drug-induced gene expression profiles, we found 36% of the active compounds regulate genes related to cholesterol homeostasis and microtubule cytoskeleton organization. Following bioinformatics analyses revealed that the expression of these genes is associated with COVID-19 patient severity and has predictive power on anti-SARS-CoV-2 efficacyin vitro. Monensin, a top new compound that regulates these genes, was further confirmed as an inhibitor of SARS-CoV-2 replication in Vero-E6 cells. Interestingly, drugs co-targeting cholesterol homeostasis and microtubule cytoskeleton organization processes more likely present a synergistic effect with antivirals. Therefore, potential therapeutics could be centered around combinations of targeting these processes and viral proteins.
