tetano
Editor, Senior Moderator
PLoS Biol
. 2024 Mar 14;22(3):e3002522.
doi: 10.1371/journal.pbio.3002522. eCollection 2024 Mar. Developing inhibitory peptides against SARS-CoV-2 envelope protein
Ramsey Bekdash[SUP] 1 2 3 [/SUP], Kazushige Yoshida[SUP] 1 2 [/SUP], Manoj S Nair[SUP] 4 [/SUP], Lauren Qiu[SUP] 1 2 5 6 [/SUP], Johnathan Ahdout[SUP] 6 [/SUP], Hsiang-Yi Tsai[SUP] 6 [/SUP], Kunihiro Uryu[SUP] 7 [/SUP], Rajesh K Soni[SUP] 8 [/SUP], Yaoxing Huang[SUP] 4 [/SUP], David D Ho[SUP] 4 9 10 [/SUP], Masayuki Yazawa[SUP] 1 2 3 6 [/SUP]
Affiliations
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected approximately 800 million people since the start of the Coronavirus Disease 2019 (COVID-19) pandemic. Because of the high rate of mutagenesis in SARS-CoV-2, it is difficult to develop a sustainable approach for prevention and treatment. The Envelope (E) protein is highly conserved among human coronaviruses. Previous studies reported that SARS-CoV-1 E deficiency reduced viral propagation, suggesting that E inhibition might be an effective therapeutic strategy for SARS-CoV-2. Here, we report inhibitory peptides against SARS-CoV-2 E protein named iPep-SARS2-E. Leveraging E-induced alterations in proton homeostasis and NFAT/AP-1 pathway in mammalian cells, we developed screening platforms to design and optimize the peptides that bind and inhibit E protein. Using Vero-E6 cells, human-induced pluripotent stem cell-derived branching lung organoid and mouse models with SARS-CoV-2, we found that iPep-SARS2-E significantly inhibits virus egress and reduces viral cytotoxicity and propagation in vitro and in vivo. Furthermore, the peptide can be customizable for E protein of other human coronaviruses such as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The results indicate that E protein can be a potential therapeutic target for human coronaviruses.
. 2024 Mar 14;22(3):e3002522.
doi: 10.1371/journal.pbio.3002522. eCollection 2024 Mar. Developing inhibitory peptides against SARS-CoV-2 envelope protein
Ramsey Bekdash[SUP] 1 2 3 [/SUP], Kazushige Yoshida[SUP] 1 2 [/SUP], Manoj S Nair[SUP] 4 [/SUP], Lauren Qiu[SUP] 1 2 5 6 [/SUP], Johnathan Ahdout[SUP] 6 [/SUP], Hsiang-Yi Tsai[SUP] 6 [/SUP], Kunihiro Uryu[SUP] 7 [/SUP], Rajesh K Soni[SUP] 8 [/SUP], Yaoxing Huang[SUP] 4 [/SUP], David D Ho[SUP] 4 9 10 [/SUP], Masayuki Yazawa[SUP] 1 2 3 6 [/SUP]
Affiliations
- PMID: 38483887
- DOI: 10.1371/journal.pbio.3002522
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected approximately 800 million people since the start of the Coronavirus Disease 2019 (COVID-19) pandemic. Because of the high rate of mutagenesis in SARS-CoV-2, it is difficult to develop a sustainable approach for prevention and treatment. The Envelope (E) protein is highly conserved among human coronaviruses. Previous studies reported that SARS-CoV-1 E deficiency reduced viral propagation, suggesting that E inhibition might be an effective therapeutic strategy for SARS-CoV-2. Here, we report inhibitory peptides against SARS-CoV-2 E protein named iPep-SARS2-E. Leveraging E-induced alterations in proton homeostasis and NFAT/AP-1 pathway in mammalian cells, we developed screening platforms to design and optimize the peptides that bind and inhibit E protein. Using Vero-E6 cells, human-induced pluripotent stem cell-derived branching lung organoid and mouse models with SARS-CoV-2, we found that iPep-SARS2-E significantly inhibits virus egress and reduces viral cytotoxicity and propagation in vitro and in vivo. Furthermore, the peptide can be customizable for E protein of other human coronaviruses such as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The results indicate that E protein can be a potential therapeutic target for human coronaviruses.