Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Aug:142:170570.
doi: 10.1016/j.peptides.2021.170570. Epub 2021 May 14.

Review of antiviral peptides for use against zoonotic and selected non-zoonotic viruses

Axel Hollmann  1 , Nancy P Cardoso  2 , Juan C Espeche  3 , Paulo C Maffía  4
Affiliations
Review

Review of antiviral peptides for use against zoonotic and selected non-zoonotic viruses

Axel Hollmann et al. Peptides. 2021 Aug.

Abstract

Viruses remain one of the leading causes of animal and human disease. Some animal viral infections spread sporadically to human populations, posing a serious health risk. Particularly the emerging viral zoonotic diseases such as the novel, zoonotic coronavirus represent an actual challenge for the scientific and medical community. Besides human health risks, some animal viral infections, although still not zoonotic, represent important economic loses to the livestock industry. Viral infections pose a genuine concern for which there has been an increasing interest for new antiviral molecules. Among these novel compounds, antiviral peptides have been proposed as promising therapeutic options, not only for the growing body of evidence showing hopeful results but also due to the many adverse effects of chemical-based drugs. Here we review the current progress, key targets and considerations for the development of antiviral peptides (AVPs). The review summarizes the state of the art of the AVPs tested in zoonotic (coronaviruses, Rift Valley fever viruses, Eastern Equine Encephalitis Virus, Dengue and Junín virus) and also non-zoonotic farm animal viruses (avian and cattle viruses). Their molecular target, amino acid sequence and mechanism of action are summarized and reviewed. Antiviral peptides are currently on the cutting edge since they have been reported to display anti-coronavirus activity. Particularly, the review will discuss the specific mode of action of AVPs that specifically inhibit the fusion of viral and host-cell membranes for SARS-CoV-2, showing in detail some important features of the fusion inhibiting peptides that target the spike protein of these risky viruses.

Keywords: Animal viruses; Antiviral peptides; Coronavirus; Zoonotic viruses.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Coronavirus viral fusion pathway based on class I fusion protein model. For simplicity, only two stages are depicted. After the S protein achieves a pre-fusion metastable state, relevant proteases enable the fusion peptide to insert in the host membrane and allow the S protein to form the pre-hairpin intermediate (a). The pre-hairpin begins to fold back on itself due to HR1 and HR2 interactions forming the bundle (b). During the S protein foldback, the two membranes will approach each other until the outer leaflets merge and eventually the inner leaflets merge (pore formation). Adapted from [99,100]. (c) Cartoon representation and closer look of the HR1-HR2 fusion core region of SARS-CoV-2. The HR motifs consist of a group of tandemly arranged seven-residue repeats. This sequence feature has the capacity to generate a hydrophobic interface along an α-helix, enabling the formation of a coiled-coil structural module when several HR-containing polypeptide chains are arranged together in parallel [101]. This fusion core is a particularly well studied target for antiviral peptides, as they can be designed in order to competitively inhibit this interaction. Relevant binding residues are labeled. Among the important amino acids responsible for the HR1-HR2 interaction, the residues colored in green may contribute to the enhanced interactions between HR1 and HR2 and stabilize 6-HB conformation of SARS-CoV- 2 compared with those of SARS-CoV (adapted from [34]).
Fig. 2
Fig. 2
Antiviral peptides mechanisms of action against coronaviruses. A) Antiviral peptides blocking the HR1 and HR2 from forming a fusion-active core, thus preventing the viral and cellular membrane fusion. For simplicity, only one monomer is represented. B) Interaction of cationic amphipatic peptide can produce viral membrane disturbance and pore formation. C) Inhibition of viral entry with peptides that interrupt the recpetor binding, like the RBD –ACE2 interaction in coronavirus infection.
Fig. 3
Fig. 3
a) Partial amino acid sequence of the surface glycoprotein of SARS-CoV-2 [ID: YP_009724390.1], where the fusion core regions of HR1 and HR2 are underlined and the candidate sequences for antiviral peptides HR1-P, HR2-P and HR2-antiP are colored. It is believed that, as it occurred in SARS-CoV, HR2-like peptide would competitively inhibits the binding of the HR2 domain to the HR1 domain, thus blocking the formation of viral fusion core, while HR1-like peptide would probably be less efficient in preventing HR1 and HR2 binding. Adapted from [33]. b) The SARS-CoV-2 S protein structure simulated by SWISS-MODEL.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bengis R.G., Leighton F.A., Fischer J.R., Artois M., Mörner T., Tate C.M. The role of wildlife in emerging and re-emerging zoonoses. OIE Rev. Sci. Tech. 2004;23:497–511. - PubMed
    1. Jones K.E., Patel N.G., Levy M.A., Storeygard A., Balk D., Gittleman J.L., Daszak P. Global trends in emerging infectious diseases. Nature. 2008;451:990–993. - PMC - PubMed
    1. Bres P., Seeliger H. Public health action in emergencies caused by epidemics. Mycoses. 2009;30 pp. 613–613.
    1. Rajeev R., Prathiviraj R., Kiran G.S., Selvin J. Zoonotic evolution and implications of microbiome in viral transmission and infection. Virus Res. 2020;290 - PMC - PubMed
    1. Beeraka N.M., Sadhu S.P., Madhunapantula S.R.V., Rao Pragada R., Svistunov A.A., Nikolenko V.N., Mikhaleva L.M., Aliev G. Strategies for targeting SARS CoV-2: small molecule inhibitors—the current status. Front. Immunol. 2020;11 - PMC - PubMed

Publication types

MeSH terms

-