Feedback

Non-covalent cyclic peptides simultaneously targeting Mpro and NRP1 are highly effective against Omicron BA.2.75

Affiliation
Department of Pharmacy ,Taizhou Hospital Affiliated to Nanjing University of Chinese Medicine ,Taizhou ,China
Yin, Shengnan;
Affiliation
Department of Pharmaceutical Analysis ,China Pharmaceutical University ,Nanjing ,China
Mei, Shuang;
Affiliation
Institute of Clinical Medicine ,Department of Pharmacy ,The Affiliated Taizhou People’s Hospital of Nanjing Medical University ,Taizhou ,China
Li, Zhiqin;
Affiliation
Institute of Clinical Medicine ,Department of Pharmacy ,The Affiliated Taizhou People’s Hospital of Nanjing Medical University ,Taizhou ,China
Xu, Zhen;
Affiliation
Institute of Clinical Medicine ,Department of Pharmacy ,The Affiliated Taizhou People’s Hospital of Nanjing Medical University ,Taizhou ,China
Wu, Yuting;
Affiliation
Institute of Clinical Medicine ,Department of Pharmacy ,The Affiliated Taizhou People’s Hospital of Nanjing Medical University ,Taizhou ,China
Chen, Xiujuan;
Affiliation
Department of Pharmacy ,Taizhou Hospital Affiliated to Nanjing University of Chinese Medicine ,Taizhou ,China
Liu, Dongmei;
Affiliation
Department of Pharmaceutical Analysis ,China Pharmaceutical University ,Nanjing ,China
Niu, Miao-Miao;
Affiliation
Institute of Clinical Medicine ,Department of Pharmacy ,The Affiliated Taizhou People’s Hospital of Nanjing Medical University ,Taizhou ,China
Li, Jindong

Available vaccine-based immunity may at high risk of being evaded due to substantial mutations in the variant Omicron. The main protease (Mpro) of SARS-CoV-2 and human neuropilin-1 (NRP1), two less mutable proteins, have been reported to be crucial for SARS-CoV-2 replication and entry into host cells, respectively. Their dual blockade may avoid vaccine failure caused by continuous mutations of the SARS-CoV-2 genome and exert synergistic antiviral efficacy. Herein, four cyclic peptides non-covalently targeting both Mpro and NRP1 were identified using virtual screening. Among them, MN-2 showed highly potent affinity to Mpro ( K d = 18.2 ± 1.9 nM) and NRP1 ( K d = 12.3 ± 1.2 nM), which was about 3,478-fold and 74-fold stronger than that of the positive inhibitors Peptide-21 and EG3287. Furthermore, MN-2 exhibited significant inhibitory activity against Mpro and remarkable anti-infective activity against the pseudotyped variant Omicron BA.2.75 without obvious cytotoxicity. These data demonstrated that MN-2, a novel non-covalent cyclic peptide, is a promising agent against Omicron BA.2.75.

Cite

Citation style:
Could not load citation form.

Access Statistic

Total:
Downloads:
Abtractviews:
Last 12 Month:
Downloads:
Abtractviews:

Rights

License Holder: Copyright © 2022 Yin, Mei, Li, Xu, Wu, Chen, Liu, Niu and Li.

Use and reproduction: