Plant-Derived Antimicrobial Peptides as Potential Antiviral Agents in Systemic Viral Infections

Abstract

Numerous studies have led to a better understanding of the mechanisms of action of viruses in systemic infections for the development of prevention strategies and very promising antiviral therapies. Viruses still remain one of the main causes of human diseases, mainly because the development of new vaccines is usually challenging and drug resistance has become an increasing concern in recent decades. Therefore, the development of potential antiviral agents remains crucial and is an unmet clinical need. One abundant source of potential therapeutic molecules are plants: they biosynthesize a myriad of compounds, including peptides which can have antimicrobial activity. Our objective is to summarize the literature on peptides with antiviral properties derived from plants and to identify key features of these peptides and their application in systemic viral infections. This literature review highlights studies including clinical trials which demonstrated that plant cyclotides have the ability to inhibit the growth of viruses causing human diseases, defensin-like peptides possess anti-HIV-1 activity, and lipid transfer proteins and some lectins exhibit a varied antimicrobial profile. To conclude, plant peptides remain interesting to explore in the context of emerging and re-emerging infectious diseases.

Improved Database Filtering Technology Enables More Efficient Ab Initio Design of Potent Peptides against Ebola Viruses

“…Antimicrobial peptides (AMPs) are an important factor of the innate immune defense for both invertebrates and vertebrates, including humans [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Recently, human defensins have been shown to inhibit SARS-CoV-2 infection [ 15 ].…”

“…These antiviral peptides can work through different mechanisms, ranging from immune regulation to direct inactivation via membrane disruption [ 17 , 18 , 19 , 20 ]. Hence, natural AMPs may be engineered into new therapeutics to help control these viruses [ 11 , 12 , 21 , 22 , 23 ]. As a proof of concept, we previously demonstrated that LL-37 could be engineered to inhibit Ebola virus entry [ 24 ].…”

In vitro Inhibition of HIV-1 by Cyclotide-Enriched Extracts of Viola tricolor

“…Plants have developed mechanisms to protect themselves against invading pathogens such as viruses, bacteria, fungi, nematodes and insects ( Mott et al, 2014 ; Nishad et al, 2020 ). Since they only have the innate immune response, a wide variety of peptides is expressed ( Mott et al, 2014 ; Mammari et al, 2021 ), many of which are rich in cysteines. Plant cysteine-rich peptides have been isolated from thousands of species ( Liu et al, 2017 ); they are extremely diverse with hundreds of different peptides produced by a single plant species.…”

“…Therefore, cyclotides represent a rich natural source of bioactive molecules with prospects for development as therapeutics against cancer and infectious diseases ( Mammari et al, 2021 ). Making use of the natural evolution, a huge variety of already optimized peptides can be assessed ( Lazzaro et al, 2020 ; Atanasov et al, 2021 ).…”

“…Peptides have a good efficacy compared to small molecules ( Wang et al, 2022 ) and a good safety profile because their degradation products are natural amino acids and they are generally less immunogenic than recombinant proteins or antibodies ( Mahlapuu et al, 2016 ). In contrary, first-generation antivirals have severe side effects due to pour specificity ( Mammari et al, 2021 ). Cyclotides are expected to be broadly active due to their direct mode of action destabilizing lipid membranes ( Henriques and Craik, 2012 ; Henriques et al, 2012 ) which will most likely prevent resistance development ( Mahlapuu et al, 2016 ; Browne et al, 2020 ; Huan et al, 2020 ).…”