tetano
Editor, Senior Moderator
EMBO Mol Med
. 2020 Nov 6;e12828.
doi: 10.15252/emmm.202012828. Online ahead of print.
Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection
Kuo-Yen Huang[SUP] 1 [/SUP], Ming-Shiu Lin[SUP] 1 [/SUP], Ting-Chun Kuo[SUP] 1 [/SUP], Ci-Ling Chen[SUP] 1 [/SUP], Chung-Chih Lin[SUP] 1 [/SUP], Yu-Chi Chou[SUP] 2 [/SUP], Tai-Ling Chao[SUP] 3 [/SUP], Yu-Hao Pang[SUP] 3 [/SUP], Han-Chieh Kao[SUP] 3 [/SUP], Rih-Sheng Huang[SUP] 4 [/SUP], Steven Lin[SUP] 4 5 [/SUP], Sui-Yuan Chang[SUP] 3 6 [/SUP], Pan-Chyr Yang[SUP] 1 7 [/SUP]
Affiliations
Abstract
To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a humanized decoy antibody (ACE2-Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2). First, we demonstrated that ACE2-Fc could specifically abrogate virus replication by blocking the entry of SARS-CoV-2 spike-expressing pseudotyped virus into both ACE2-expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS-CoV-2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2-Fc to reduce the angiotensin II-mediated cytokine cascade. Furthermore, this Fc domain of ACE2-Fc was shown to activate NK cell degranulation after coincubation with Spike-expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2-Fc as an effective treatment for COVID-19.
Keywords: ACE2-Fc; COVID-19; SARS-CoV-2; decoy antibody; virus infection.
. 2020 Nov 6;e12828.
doi: 10.15252/emmm.202012828. Online ahead of print.
Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection
Kuo-Yen Huang[SUP] 1 [/SUP], Ming-Shiu Lin[SUP] 1 [/SUP], Ting-Chun Kuo[SUP] 1 [/SUP], Ci-Ling Chen[SUP] 1 [/SUP], Chung-Chih Lin[SUP] 1 [/SUP], Yu-Chi Chou[SUP] 2 [/SUP], Tai-Ling Chao[SUP] 3 [/SUP], Yu-Hao Pang[SUP] 3 [/SUP], Han-Chieh Kao[SUP] 3 [/SUP], Rih-Sheng Huang[SUP] 4 [/SUP], Steven Lin[SUP] 4 5 [/SUP], Sui-Yuan Chang[SUP] 3 6 [/SUP], Pan-Chyr Yang[SUP] 1 7 [/SUP]
Affiliations
- PMID: 33159417
- DOI: 10.15252/emmm.202012828
Abstract
To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a humanized decoy antibody (ACE2-Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2). First, we demonstrated that ACE2-Fc could specifically abrogate virus replication by blocking the entry of SARS-CoV-2 spike-expressing pseudotyped virus into both ACE2-expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS-CoV-2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2-Fc to reduce the angiotensin II-mediated cytokine cascade. Furthermore, this Fc domain of ACE2-Fc was shown to activate NK cell degranulation after coincubation with Spike-expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2-Fc as an effective treatment for COVID-19.
Keywords: ACE2-Fc; COVID-19; SARS-CoV-2; decoy antibody; virus infection.