Supercoiling Structure-Based Design of a Trimeric Coiled-Coil Peptide with High Potency against HIV-1 and Human beta-Coronavirus Infection
Journal of Medicinal Chemistry
; 30:30, 2021.
Article
in English
| MEDLINE | ID: covidwho-1210153
ABSTRACT
Hexameric structure formation through packing of three C-terminal helices and an N-terminal trimeric coiled-coil core has been proposed as a general mechanism of class I enveloped virus entry. In this process, the C-terminal helical repeat (HR2) region of viral membrane fusion proteins becomes transiently exposed and accessible to N-terminal helical repeat (HR1) trimer-based fusion inhibitors. Herein, we describe a mimetic of the HIV-1 gp41 HR1 trimer, N3G, as a promising therapeutic against HIV-1 infection. Surprisingly, we found that in addition to protection against HIV-1 infection, N3G was also highly effective in inhibiting infection of human beta-coronaviruses, including MERS-CoV, HCoV-OC43, and SARS-CoV-2, possibly by binding the HR2 region in the spike protein of beta-coronaviruses to block their hexameric structure formation. These studies demonstrate the potential utility of anti-HIV-1 HR1 peptides in inhibiting human beta-coronavirus infection. Moreover, this strategy could be extended to the design of broad-spectrum antivirals based on the supercoiling structure of peptides.
Full text:
Available
Collection:
Databases of international organizations
Database:
MEDLINE
Language:
English
Journal:
Journal of Medicinal Chemistry
Year:
2021
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS