Bomidin: An Optimized Antimicrobial Peptide With Broad Antiviral Activity Against Enveloped Viruses

Abstract

The rapid evolution of highly infectious pathogens is a major threat to global public health. In the front line of defense against bacteria, fungi, and viruses, antimicrobial peptides (AMPs) are naturally produced by all living organisms and offer new possibilities for next-generation antibiotic development. However, the low yields and difficulties in the extraction and purification of AMPs have hindered their industry and scientific research applications. To overcome these barriers, we enabled high expression of bomidin, a commercial recombinant AMP based upon bovine myeloid antimicrobial peptide-27. This novel AMP, which can be expressed in Escherichia coli by adding methionine to the bomidin sequence, can be produced in bulk and is more biologically active than chemically synthesized AMPs. We verified the function of bomidin against a variety of bacteria and enveloped viruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), herpes simplex virus (HSV), dengue virus (DENV), and chikungunya virus (CHIKV). Furthermore, based on the molecular modeling of bomidin and membrane lipids, we elucidated the possible mechanism by which bomidin disrupts bacterial and viral membranes. Thus, we obtained a novel AMP with an optimized, efficient heterologous expression system for potential therapeutic application against a wide range of life-threatening pathogens.

A review of the antiviral activity of cationic antimicrobial peptides

“…Most studies have examined the effect of AVPs on human immunodeficiency virus (HIV) [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , 73 peptides demonstrated antiviral activity against HIV, 47 peptides were active against herpes viruses [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , 27 peptides active against hepatitis C virus (HCV) [54] , [55] , [56] , [57] , [58] , [59] , 11 were active against human coronaviruses [39] , [52] , [53] , [60] , [61] , [62] , [63] , [64] , [65] , and 9 showing antiviral activity against the influenza virus [39] , [61] , …”

“…Several AVPs target herpes simplex viruses HSV-1 and HSV-2. Some of these AVPs directly interact with the virion structure, disrupting or disturbing membrane integrity or aggregating virion particles, including temporin L (derived from European frog), TL1(a synthetic peptide) [39] , MCP-1,2 (isolated from rabbit leukocytes) [40] , MOD-1 (synthetic) [41] , hectate (synthetic peptide analogue of melittin) [42] , indolicidin [43] , [47] , CAM-brevinin-1(brevinin-1 synthetic analog) [43] , dermaseptin S4 [44] and it’s synthetic derivatives [51] , bomodin (a recombinant AMP based upon BMAP-27) [53] , and gB122 (a synthetic peptide) [50] . The net charge of these peptides ranged from +2 to +10, aliphatic index from 19.33 to 146.79, and the GRAVY score from -1.121 to +1.288.…”

Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin

“…To model the membrane-bound PETase, PETase-GCW51 and HFBI-GCW61 were anchored to a bilayer of lipids through glycosylphosphatidylinositol modifications at protein N-termini. A typical composition of lipids included 66 molecules of ergosterol, 32 molecules of POPA, 64 molecules of POPC, 60 molecules of POPE, and 96 molecules of POPI to mimic the yeast membrane environment and maintain the bilayer stability (15 nm × 15 nm in the xy dimension) 88 , 89 . To mimic PET plastic in a possible solvent-swelling state, 20 individual chains of 4PET were added to the system at random positions along with 6 nm thickness of TIP3P waters and ions (0.15 M NaCl), the resulting system contained a total of 343086 atoms.…”

Designed Multifunctional Peptides for Intracellular Targets

“…Recently, experimentalists confirmed broad activity against enveloped viruses by the second bovine cathelicidin fragment with the sequence GRFKRFRKKFKKLFKKIS [ 179 ]. It was derived from BMAP-27 [ 314 ].…”