This class of peptide is characterized by its pre-pro peptide structure formed by an N-terminal signal peptide and C-terminal antimicrobial domain flanking a highly conserved cathelin-like domain. Later efforts to capture the full-length cDNA of Bac-5 would serendipitously discover that Dodecapeptide, Bac-5, and Bac-7 all contained the same N-terminal pro-region with high sequence similarity to porcine cathelin 11, 12.ĭodecapeptide, Bac-5, and Bac-7, along with many other examples from mammals, birds, and some fish belong to the family of host defense peptides called cathelicidins, which possess broad antimicrobial activity 13, 14, 15. In 19, the field of host defense peptides broadened with the elegant discovery of the antibacterial bactenecins Dodecapeptide, Bac-5, and Bac-7 in the cytoplasmic granules of bovine neutrophils 9, 10. Some of the most notable examples include human lysozyme discovered by Alexander Fleming in the 1920s, the peptide melittin isolated from bee venom, magainins isolated from the frog Xenopus laevis, as well as a family of peptides released from the granules of neutrophils that have broad-spectrum antimicrobial and antiviral capabilities called defensins 4, 5, 6, 7, 8. Following this discovery, many other similar peptides that were discovered previously were identified as host defense peptides. This was the first isolated host defense peptide, which they called cecropin 3. In 1981, Hans Boman and colleagues demonstrated that the silkworms survive bacterial infection because of a peptide in the worms’ hemolymph. Plants and insects lack an adaptative immune system, but they can effectively fight microbial invasion by producing host defense peptides. The continued spread of SARS-CoV-2 and the potential emergence of highly transmissible variants of concern and eventually a fully vaccine-resistant strain mandates the need for new therapeutic antivirals in addition to ongoing vaccine improvements. Since first emerging in China, SARS-CoV-2 has spread globally and diverged into multiple variants with mutations permitting enhanced transmissibility and even escape from neutralizing antibodies generated by previous infection or vaccination with the original A.1 strain and A.1 spike-based vaccines 2. SARS-CoV-2 shares over 96% genome sequence identity with a known bat coronavirus, suggesting a recent zoonotic transmission event 1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the newest member of the human Beta-coronavirus group and the causative agent of “coronavirus infectious disease 2019” (COVID-19), a disease characterized often by life-threatening viral pneumonia. Interestingly, it inhibits all drifted variants of SARS CoV-2 that we tested, including the alpha, beta, gamma, delta, kappa and omicron variants. Yongshi also binds to the heptad repeat 1 of SARS-CoV-1 and MERS-CoV. Experimental data confirm the binding of Yongshi to the heptad repeat 1 with a fourfold higher affinity than heptad repeat 2 of SARS-CoV-2. A deep learning-based protein sequence comparison algorithm and molecular modeling suggest that Yongshi acts as a mimetic to the heptad repeats of the virus, thereby disrupting the fusion process. Following the binding of SARS-CoV-2 to its receptor, the spike protein is cleaved, and heptad repeats 1 and 2 multimerize to form the fusion complex that enables the virion to enter the cell. This peptide, which we named Yongshi and means warrior in Mandarin, acts as a viral entry inhibitor. We screened the cathelicidin family of peptides from 16 different species for antiviral activity and identified a wild boar peptide derivative that inhibits SARS CoV-2. Host defense peptides represent a potential source for such an antiviral as they possess broad antimicrobial activity and significant diversity across species. A complimentary solution to this problem could be developing antiviral drugs that inhibit SARS CoV-2 and its drifted variants.
Peptide sequences full#
Even when full vaccine coverage is achieved, vaccine-resistant mutants will likely emerge, thus requiring new annual vaccines against drifted variants analogous to influenza. To control the pandemic, multiple effective vaccines have been developed, and global vaccinations are in progress. It has infected over 200 million and killed 4 million people worldwide, and infections continue with no end in sight. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a clear threat to humanity.
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