A pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery

Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into multiple variants. These variants, especially Omicron, reportedly escape therapeutic antibodies and vaccines, indicating an urgent ne...

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Bibliographic Details
Published in:Science China. Life sciences 2023-10, Vol.66 (10), p.2201-2213
Main Authors: Wu, Lili, Zheng, Anqi, Tang, Yangming, Chai, Yan, Chen, Jiantao, Cheng, Lin, Hu, Yu, Qu, Jing, Lei, Wenwen, Liu, William Jun, Wu, Guizhen, Zeng, Shaogui, Yang, Hang, Wang, Qihui, Gao, George Fu
Format: Article
Language:English
Subjects:
Antiviral activity
Antiviral agents
Biomedical and Life Sciences
Coronaviruses
Cover Article
Intranasal administration
Life Sciences
Peptide inhibitors
Peptides
Severe acute respiratory syndrome coronavirus 2
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Summary:Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into multiple variants. These variants, especially Omicron, reportedly escape therapeutic antibodies and vaccines, indicating an urgent need for new antivirals with pan-SARS-CoV-2 inhibitory activity. We previously reported that a peptide fusion inhibitor, P3, targeting heptad repeated-1 (HR1) of SARS-CoV-2 spike (S) protein, could inhibit viral infections. Here, we further designed multiple derivatives of the P3 based on structural analysis and found that one derivative, the P315V3, showed the most efficient antiviral activity against SARS-CoV-2 variants and several other sarbecoviruses, as well as other human-CoVs (HCoVs). P315V3 also exhibited effective prophylactic efficacy against the SARS-CoV-2 Delta and Omicron variants in mice via intranasal administration. These results suggest that P315V3, which is in Phase II clinical trial, is promising for further development as a nasal pan-SARS-CoV-2 or pan-CoVs inhibitor to prevent or treat CoV diseases.
ISSN:1674-7305
1869-1889
DOI:10.1007/s11427-023-2410-5