tetano
Editor, Senior Moderator
Bioorg Med Chem Lett
. 2023 Nov 24:129569.
doi: 10.1016/j.bmcl.2023.129569. Online ahead of print. Design of MERS-CoV Entry Inhibitory Short Peptides Based on Helix-stabilizing Strategies
Jichun Li[SUP] 1 [/SUP], Qing Li[SUP] 2 [/SUP], Shuai Xia[SUP] 3 [/SUP], Jiahuang Tu[SUP] 2 [/SUP], Longbo Zheng[SUP] 4 [/SUP], Qian Wang[SUP] 3 [/SUP], Shibo Jiang[SUP] 5 [/SUP], Chao Wang[SUP] 6 [/SUP]
Affiliations
Interaction between Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) protein heptad repeat-1 domain (HR1) and heptad repeat-2 domain (HR2) is critical for the MERS-CoV fusion process. This interaction is mediated by the α-helical region from HR2 and the hydrophobic groove in a central HR1 trimeric coiled coil. We sought to develop a short peptidomimetic to act as a MERS-CoV fusion inhibitor by reproducing the key recognition features of HR2 helix. This was achieved by the use of helix-stabilizing strategies, including substitution with unnatural helix-favoring amino acids, introduction of ion pair interactions, and conjugation of palmitic acid. The resulting 23-mer lipopeptide, termed AEEA-C16, inhibits MERS-CoV S protein-mediated cell-cell fusion at a low micromolar level comparable to that of the 36-mer HR2 peptide HR2P-M2. Collectively, our studies provide new insights into developing short peptide-based antiviral agents to treat MERS-CoV infection.
Keywords: MERS-CoV; fusion inhibitor; lipopeptide; membrane fusion; α-helices.
. 2023 Nov 24:129569.
doi: 10.1016/j.bmcl.2023.129569. Online ahead of print. Design of MERS-CoV Entry Inhibitory Short Peptides Based on Helix-stabilizing Strategies
Jichun Li[SUP] 1 [/SUP], Qing Li[SUP] 2 [/SUP], Shuai Xia[SUP] 3 [/SUP], Jiahuang Tu[SUP] 2 [/SUP], Longbo Zheng[SUP] 4 [/SUP], Qian Wang[SUP] 3 [/SUP], Shibo Jiang[SUP] 5 [/SUP], Chao Wang[SUP] 6 [/SUP]
Affiliations
- PMID: 38008340
- DOI: 10.1016/j.bmcl.2023.129569
Interaction between Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) protein heptad repeat-1 domain (HR1) and heptad repeat-2 domain (HR2) is critical for the MERS-CoV fusion process. This interaction is mediated by the α-helical region from HR2 and the hydrophobic groove in a central HR1 trimeric coiled coil. We sought to develop a short peptidomimetic to act as a MERS-CoV fusion inhibitor by reproducing the key recognition features of HR2 helix. This was achieved by the use of helix-stabilizing strategies, including substitution with unnatural helix-favoring amino acids, introduction of ion pair interactions, and conjugation of palmitic acid. The resulting 23-mer lipopeptide, termed AEEA-C16, inhibits MERS-CoV S protein-mediated cell-cell fusion at a low micromolar level comparable to that of the 36-mer HR2 peptide HR2P-M2. Collectively, our studies provide new insights into developing short peptide-based antiviral agents to treat MERS-CoV infection.
Keywords: MERS-CoV; fusion inhibitor; lipopeptide; membrane fusion; α-helices.