A detailed study of ion transport through the SARS-CoV-2 E protein ion channel

Saurabh, Kumar; Solovchuk, Maxim; Sheu, Tony W. H.

doi:10.1039/d2nr01385a

Cited by 4 publications

(1 citation statement)

References 44 publications

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“…Therefore, it would be ideal if we could target coronavirus genes that are highly conserved in SARS-CoV-1 and SARS-CoV-2 variants, as well as other human coronaviruses. Human coronaviruses such as SARS-CoV-2 and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) express an Envelope (E) protein that forms an ion channel essential for viral function called a viroporin [11][12][13][14][15][16][17]. E protein is known to induce cellular toxicity via a number of different molecules and signaling pathways [12,16,[18][19][20][21][22][23]] and E protein is also thought to be involved in the Spike protein protection and maturation in host cells [20,24].…”

Section: Introductionmentioning

confidence: 99%

Developing inhibitory peptides against SARS-CoV-2 envelope protein

Bekdash,

Yoshida,

Nair

et al. 2024

PLoS Biol

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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.

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