tetano
Editor, Senior Moderator
J Med Virol
. 2023 Jul;95(7):e28965.
doi: 10.1002/jmv.28965. Redirecting the JAK-STAT signal blocks the SARS-CoV-2 replication
George Augustine[SUP] 1 2 [/SUP], Valappil Sisila[SUP] 1 3 [/SUP], Mohan Indhu[SUP] 1 3 [/SUP], Divya Gupta[SUP] 4 [/SUP], Dixit Tandel[SUP] 4 [/SUP], Krishnan Harinivas Harshan[SUP] 4 [/SUP], Ganesh Shanmugam[SUP] 3 5 [/SUP], Padmanabhan Padmapriya[SUP] 6 [/SUP], Srinivasan Sivasubramanian[SUP] 6 [/SUP], Krishnaswamy Kaveri[SUP] 6 [/SUP], Kamini Numbi Ramudu[SUP] 1 3 [/SUP], Niraikulam Ayyadurai[SUP] 1 3 4 [/SUP]
Affiliations
The distinct disease progression patterns of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) indicate diverse host immune responses. SARS-CoV-2 severely impairs type I interferon (IFN) cell signaling, resulting in uncontrolled late-phase lung damage in patients. For better pharmacological properties, cytokine modifications may sometimes result in a loss of biological activity against the virus. Here, we employed the genetic code expansion and engineered IFN-β, a phase II clinical cytokine with 3-amino tyrosine (IFN-β-A) that reactivates STAT2 expression in virus-infected human cells through JAK/STAT cell signaling without affecting signal activation and serum half-life. This study identified that genetically encoded IFN-β-A might stabilize the protein-receptor complex and trigger JAK-STAT cell signaling, which is a promising modality for controlling SARS-CoV-2 infection.
Keywords: JAK-STAT pathway; SARS-CoV-2; STAT2; genetic code expansion; interferon-β; unnatural amino acid; virus.
. 2023 Jul;95(7):e28965.
doi: 10.1002/jmv.28965. Redirecting the JAK-STAT signal blocks the SARS-CoV-2 replication
George Augustine[SUP] 1 2 [/SUP], Valappil Sisila[SUP] 1 3 [/SUP], Mohan Indhu[SUP] 1 3 [/SUP], Divya Gupta[SUP] 4 [/SUP], Dixit Tandel[SUP] 4 [/SUP], Krishnan Harinivas Harshan[SUP] 4 [/SUP], Ganesh Shanmugam[SUP] 3 5 [/SUP], Padmanabhan Padmapriya[SUP] 6 [/SUP], Srinivasan Sivasubramanian[SUP] 6 [/SUP], Krishnaswamy Kaveri[SUP] 6 [/SUP], Kamini Numbi Ramudu[SUP] 1 3 [/SUP], Niraikulam Ayyadurai[SUP] 1 3 4 [/SUP]
Affiliations
- PMID: 37488710
- DOI: 10.1002/jmv.28965
The distinct disease progression patterns of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) indicate diverse host immune responses. SARS-CoV-2 severely impairs type I interferon (IFN) cell signaling, resulting in uncontrolled late-phase lung damage in patients. For better pharmacological properties, cytokine modifications may sometimes result in a loss of biological activity against the virus. Here, we employed the genetic code expansion and engineered IFN-β, a phase II clinical cytokine with 3-amino tyrosine (IFN-β-A) that reactivates STAT2 expression in virus-infected human cells through JAK/STAT cell signaling without affecting signal activation and serum half-life. This study identified that genetically encoded IFN-β-A might stabilize the protein-receptor complex and trigger JAK-STAT cell signaling, which is a promising modality for controlling SARS-CoV-2 infection.
Keywords: JAK-STAT pathway; SARS-CoV-2; STAT2; genetic code expansion; interferon-β; unnatural amino acid; virus.