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C-Terminal Lipidation of SARS-CoV-2 Fusion Peptide Reinstates Superior Membrane Fusion Catalytic Ability.
Sardar, Avijit; Bera, Tapas; Samal, Santosh Kumar; Dewangan, Nikesh; Kamble, Mithila; Guha, Samit; Tarafdar, Pradip Kumar.
  • Sardar A; IISER Kolkata: Indian Institute of Science Education and Research Kolkata, Chemical Sciences, INDIA.
  • Bera T; Jadavpur University, Chemistry, INDIA.
  • Samal SK; IISER Kolkata: Indian Institute of Science Education and Research Kolkata, Biological Sciences, INDIA.
  • Dewangan N; IISER Kolkata: Indian Institute of Science Education and Research Kolkata, Chemical Sciences, INDIA.
  • Kamble M; IISER Kolkata: Indian Institute of Science Education and Research Kolkata, Biological Sciences, INDIA.
  • Guha S; Jadavpur University, Chemistry, INDIA.
  • Tarafdar PK; "Indian Institute of Science Education and Research Kolkata", Chemical Sciences, Research Complex, 741246, Mohanpur, INDIA.
Chemistry ; 2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2279838
ABSTRACT
The Spike (S) protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) mediates a critical stage in infection, the fusion between viral and host membranes. The protein is categorized as a class I viral fusion protein and has two distinct cleavage sites that can be activated by proteases. The activation deploys the fusion peptide (FP) for insertion into the target cell membranes. Recent studies including our experiments showed that the FP was unable to modulate the kinetics of fusion at a low peptide-to-lipid ratio akin to the spike density at the viral surface. Therefore, we have modified the C-terminus of FP and attached a myristoyl chain (C-myr-FP) to restrict the C-terminus near to interface, bridge both membranes, and increase the effective local concentration. The lipidated FP (C-myr-FP) of SARS-CoV-2 greatly accelerates membrane fusion at a low peptide-to-lipid ratio as compared to the FP with no lipidation. Biophysical experiments suggest that C-myr-FP adopts a helical structure, perturbs the membrane interface, and increases water penetration to catalyze fusion. Scrambled peptide (C-myr-sFP) and truncated peptide (C-myr-8FP) couldn't significantly catalyze the fusion suggesting the important role of myristoylation and the N-terminus. C-myr-FP enhances the murine coronavirus infection by promoting syncytia formation in L2 cells. The C-terminal lipidation of the FP may be a useful strategy to induce artificial fusion in biomedical applications.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal subject: Chemistry Year: 2022 Document Type: Article Affiliation country: Chem.202203034

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal subject: Chemistry Year: 2022 Document Type: Article Affiliation country: Chem.202203034