tetano
Editor, Senior Moderator
J Virol
. 2022 Dec 5;e0124522.
doi: 10.1128/jvi.01245-22. Online ahead of print.
Sertraline Is an Effective SARS-CoV-2 Entry Inhibitor Targeting the Spike Protein
Yuliu Chen[SUP] #[/SUP][SUP] 1 [/SUP], Yan Wu[SUP] #[/SUP][SUP] 2 [/SUP], Shaoying Chen[SUP] 1 [/SUP], Qingping Zhan[SUP] 1 [/SUP], Dingzhou Wu[SUP] 1 [/SUP], Chan Yang[SUP] 1 [/SUP], Xiaoxue He[SUP] 2 [/SUP], Mengjie Qiu[SUP] 1 [/SUP], Nannan Zhang[SUP] 3 [/SUP], Zhaofeng Li[SUP] 1 [/SUP], Yunhua Guo[SUP] 4 [/SUP], Minjun Wen[SUP] 1 [/SUP], Lu Lu[SUP] 5 [/SUP], Cuiqing Ma[SUP] 6 [/SUP], Jiayin Guo[SUP] 1 [/SUP], Wei Xu[SUP] 1 [/SUP], Xiaojuan Li[SUP] 1 [/SUP], Lin Li[SUP] 1 [/SUP], Shibo Jiang[SUP] 5 [/SUP], Xiaoyan Pan[SUP] 2 [/SUP], Shuwen Liu[SUP] 1 [/SUP], Suiyi Tan[SUP] 1 [/SUP]
Affiliations
Abstract
The global spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuously emerging new variants underscore an urgent need for effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). Here, we screened several FDA-approved amphiphilic drugs and determined that sertraline (SRT) exhibits potent antiviral activity against infection of SARS-CoV-2 pseudovirus (PsV) and authentic virus in vitro. It effectively inhibits SARS-CoV-2 spike (S)-mediated cell-cell fusion. SRT targets the early stage of viral entry. It can bind to the S1 subunit of the S protein, especially the receptor binding domain (RBD), thus blocking S-hACE2 interaction and interfering with the proteolysis process of S protein. SRT is also effective against infection with SARS-CoV-2 PsV variants, including the newly emerging Omicron. The combination of SRT and other antivirals exhibits a strong synergistic effect against infection of SARS-CoV-2 PsV. The antiviral activity of SRT is independent of serotonin transporter expression. Moreover, SRT effectively inhibits infection of SARS-CoV-2 PsV and alleviates the inflammation process and lung pathological alterations in transduced mice in vivo. Therefore, SRT shows promise as a treatment option for COVID-19. IMPORTANCE The study shows SRT is an effective entry inhibitor against infection of SARS-CoV-2, which is currently prevalent globally. SRT targets the S protein of SARS-CoV-2 and is effective against a panel of SARS-CoV-2 variants. It also could be used in combination to prevent SARS-CoV-2 infection. More importantly, with long history of clinical use and proven safety, SRT might be particularly suitable to treat infection of SARS-CoV-2 in the central nervous system and optimized for treatment in older people, pregnant women, and COVID-19 patients with heart complications, which are associated with severity and mortality of COVID-19.
Keywords: SARS-CoV-2; entry inhibitor; inflammation; sertraline; spike.
. 2022 Dec 5;e0124522.
doi: 10.1128/jvi.01245-22. Online ahead of print.
Sertraline Is an Effective SARS-CoV-2 Entry Inhibitor Targeting the Spike Protein
Yuliu Chen[SUP] #[/SUP][SUP] 1 [/SUP], Yan Wu[SUP] #[/SUP][SUP] 2 [/SUP], Shaoying Chen[SUP] 1 [/SUP], Qingping Zhan[SUP] 1 [/SUP], Dingzhou Wu[SUP] 1 [/SUP], Chan Yang[SUP] 1 [/SUP], Xiaoxue He[SUP] 2 [/SUP], Mengjie Qiu[SUP] 1 [/SUP], Nannan Zhang[SUP] 3 [/SUP], Zhaofeng Li[SUP] 1 [/SUP], Yunhua Guo[SUP] 4 [/SUP], Minjun Wen[SUP] 1 [/SUP], Lu Lu[SUP] 5 [/SUP], Cuiqing Ma[SUP] 6 [/SUP], Jiayin Guo[SUP] 1 [/SUP], Wei Xu[SUP] 1 [/SUP], Xiaojuan Li[SUP] 1 [/SUP], Lin Li[SUP] 1 [/SUP], Shibo Jiang[SUP] 5 [/SUP], Xiaoyan Pan[SUP] 2 [/SUP], Shuwen Liu[SUP] 1 [/SUP], Suiyi Tan[SUP] 1 [/SUP]
Affiliations
- PMID: 36468859
- DOI: 10.1128/jvi.01245-22
Abstract
The global spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuously emerging new variants underscore an urgent need for effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). Here, we screened several FDA-approved amphiphilic drugs and determined that sertraline (SRT) exhibits potent antiviral activity against infection of SARS-CoV-2 pseudovirus (PsV) and authentic virus in vitro. It effectively inhibits SARS-CoV-2 spike (S)-mediated cell-cell fusion. SRT targets the early stage of viral entry. It can bind to the S1 subunit of the S protein, especially the receptor binding domain (RBD), thus blocking S-hACE2 interaction and interfering with the proteolysis process of S protein. SRT is also effective against infection with SARS-CoV-2 PsV variants, including the newly emerging Omicron. The combination of SRT and other antivirals exhibits a strong synergistic effect against infection of SARS-CoV-2 PsV. The antiviral activity of SRT is independent of serotonin transporter expression. Moreover, SRT effectively inhibits infection of SARS-CoV-2 PsV and alleviates the inflammation process and lung pathological alterations in transduced mice in vivo. Therefore, SRT shows promise as a treatment option for COVID-19. IMPORTANCE The study shows SRT is an effective entry inhibitor against infection of SARS-CoV-2, which is currently prevalent globally. SRT targets the S protein of SARS-CoV-2 and is effective against a panel of SARS-CoV-2 variants. It also could be used in combination to prevent SARS-CoV-2 infection. More importantly, with long history of clinical use and proven safety, SRT might be particularly suitable to treat infection of SARS-CoV-2 in the central nervous system and optimized for treatment in older people, pregnant women, and COVID-19 patients with heart complications, which are associated with severity and mortality of COVID-19.
Keywords: SARS-CoV-2; entry inhibitor; inflammation; sertraline; spike.