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Fulltext Identification and characterisation of a novel anti-viral peptide against avian influenza virus H9N2

Rajik M, Jahanshiri F, Omar AR, Ideris A, Hassan SS, Yusoff K

Virol J, 2009;6:74.
PMID: 19497129 DOI: 10.1186/1743-422X-6-74

Avian influenza viruses (AIV) cause high morbidity and mortality among the poultry worldwide. Their highly mutative nature often results in the emergence of drug resistant strains, which have the potential of causing a pandemic. The virus has two immunologically important glycoproteins, hemagglutinin (HA), neuraminidase (NA), and one ion channel protein M2 which are the most important targets for drug discovery, on its surface. In order to identify a peptide-based virus inhibitor against any of these surface proteins, a disulfide constrained heptapeptide phage display library was biopanned against purified AIV sub-type H9N2 virus particles.

Matched MeSH terms: Peptides/pharmacology*
A novel peptide inhibits the influenza virus replication by preventing the viral attachment to the host cells

Rajik M, Omar AR, Ideris A, Hassan SS, Yusoff K

Int J Biol Sci, 2009 Aug 08;5(6):543-8.
PMID: 19680476

Avian influenza viruses (AIV), the causative agent of avian flu or bird flu, cause widespread morbidity and mortality in poultry. The symptoms of the disease range from mild flu like symptoms to death. These viruses possess two important surface glycoproteins, namely hemagglutinin (HA) and neuraminidase (NA) against which neutralizing antibodies are produced. Due to the highly mutative nature of the genes which encode these proteins, the viruses often confer resistance to the current anti-viral drugs making the prevention and treatment of infection challenging. In our laboratory, we have recently identified a novel anti-viral peptide (P1) against the AIV H9N2 from a phage displayed peptide library. This peptide inhibits the replication of the virus in ovo and in vitro by its binding to the HA glycoprotein. In the current study, we demonstrate that the peptide inhibits the virus replication by preventing the attachment to the host cell but it does not have any effect on the viral fusion. The reduction in the viral nucleoprotein (NP) expression inside the host cell has also been observed during the peptide (P1) treatment. This novel peptide may have the potential to be developed as a therapeutic agent for the treatment and control of avian influenza virus H9N2 infections.

Matched MeSH terms: Peptides/pharmacology*
Inhibitory effects of a peptide-fusion protein (Latarcin-PAP1-Thanatin) against chikungunya virus

Rothan HA, Bahrani H, Shankar EM, Rahman NA, Yusof R

Antiviral Res, 2014 Aug;108:173-80.
PMID: 24929084 DOI: 10.1016/j.antiviral.2014.05.019

Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the available treatment strategies can only alleviate disease symptoms, and no effective therapeutics or vaccines are currently available for human use. Here, we report the use of a new cost-effective approach involving production of a recombinant antiviral peptide-fusion protein that is scalable for the treatment of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1 antiviral protein, and the Thanatin (THAN) peptide to the C-terminus, was produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN protein showed 89.0% reduction of viral plaque formation compared with PAP1 (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein reduced the viral RNA load that was 0.89-fold compared with the untreated control cells. We also showed that PAP1 resulted in 0.44-fold reduction, and THAN and LATA resulting in 0.78-fold and 0.73-fold reductions, respectively. The LATA-PAP1-THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of 11.2μg/ml, which is approximately half of the EC50 of PAP1 (23.7μg/ml) and protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that production of antiviral peptide-fusion protein in E. coli as inclusion bodies could accentuate antiviral activities, enhance cellular internalisation, and could reduce product toxicity to host cells and is scalable to epidemic response quantities.

Matched MeSH terms: Antimicrobial Cationic Peptides/pharmacology
Fulltext Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide

Rothan HA, Mohamed Z, Suhaeb AM, Rahman NA, Yusof R

OMICS, 2013 Nov;17(11):560-7.
PMID: 24044366 DOI: 10.1089/omi.2013.0056

Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.

Matched MeSH terms: Peptides/pharmacology*; Antimicrobial Cationic Peptides/pharmacology*
Fulltext Scalable Production of Recombinant Membrane Active Peptides and Its Potential as a Complementary Adjunct to Conventional Chemotherapeutics

Rothan HA, Ambikabothy J, Abdulrahman AY, Bahrani H, Golpich M, Amini E, et al.

PLoS One, 2015;10(9):e0139248.
PMID: 26418816 DOI: 10.1371/journal.pone.0139248

The production of short anticancer peptides in recombinant form is an alternative method for costly chemical manufacturing. However, the limitations of host toxicity, bioactivity and column purification have impaired production in mass quantities. In this study, short cationic peptides were produced in aggregated inclusion bodies by double fusion with a central protein that has anti-cancer activity. The anticancer peptides Tachiplicin I (TACH) and Latarcin 1 (LATA) were fused with the N- and C-terminus of the MAP30 protein, respectively. We successfully produced the recombinant TACH-MAP30-LATA protein and MAP30 alone in E. coli that represented 59% and 68% of the inclusion bodies. The purified form of the inclusion bodies was prepared by eliminating host cell proteins through multiple washing steps and semi-solubilization in alkaline buffer. The purified active protein was recovered by inclusive solubilization at pH 12.5 in the presence of 2 M urea and refolded in alkaline buffer containing oxides and reduced glutathione. The peptide-fusion protein showed lower CC50 values against cancer cells (HepG2, 0.35±0.1 μM and MCF-7, 0.58±0.1 μM) compared with normal cells (WRL68, 1.83±0.2 μM and ARPE19, 2.5±0.1 μM) with outstanding activity compared with its individual components. The presence of the short peptides facilitated the entry of the peptide fusion protein into cancer cells (1.8 to 2.2-fold) compared with MAP30 alone through direct interaction with the cell membrane. The cancer chemotherapy agent doxorubicin showed higher efficiency and selectivity against cancer cells in combination with the peptide- fusion protein. This study provides new data on the mass production of short anticancer peptides as inclusion bodies in E. coli by fusion with a central protein that has similar activity. The product was biologically active against cancer cells compared with normal cells and enhanced the activity and selective delivery of an anticancer chemotherapy agent.

Matched MeSH terms: Peptides/pharmacology*
Fulltext Identification of natural antimicrobial agents to treat dengue infection: In vitro analysis of latarcin peptide activity against dengue virus

Rothan HA, Bahrani H, Rahman NA, Yusof R

BMC Microbiol, 2014;14:140.
PMID: 24885331 DOI: 10.1186/1471-2180-14-140

Although there have been considerable advances in the study of dengue virus, no vaccines or anti-dengue drugs are currently available for humans. Therefore, new approaches are necessary for the development of potent anti-dengue drugs. Natural antimicrobial peptides (AMPs) with potent antiviral activities are potential hits-to-leads for antiviral drug discovery. We performed this study to identify and characterise the inhibitory potential of the latarcin peptide (Ltc 1, SMWSGMWRRKLKKLRNALKKKLKGE) against dengue virus replication in infected cells.

Matched MeSH terms: Antimicrobial Cationic Peptides/pharmacology
Fulltext Protegrin-1 inhibits dengue NS2B-NS3 serine protease and viral replication in MK2 cells

Rothan HA, Abdulrahman AY, Sasikumer PG, Othman S, Rahman NA, Yusof R

J Biomed Biotechnol, 2012;2012:251482.
PMID: 23093838 DOI: 10.1155/2012/251482

Dengue diseases have an economic as well as social burden worldwide. In this study, the antiviral activity of protegrin-1 (PG-1, RGGRLCYCRRRFCVCVGR) peptide towards dengue NS2B-NS3pro and viral replication in Rhesus monkey kidney (MK2) cells was investigated. The peptide PG-1 was synthesized by solid-phase peptide synthesis, and disulphide bonds formation followed by peptide purification was confirmed by LC-MS and RPHPLC. Dengue NS2B-NS3pro was produced as a single-chain recombinant protein in E. coli. The NS2B-NS3pro assay was carried out by measuring the florescence emission of catalyzed substrate. Real-time PCR was used to evaluate the inhibition potential of PG-1 towards dengue serotype-2 (DENV-2) replication in MK2 cells. The results showed that PG-1 inhibited dengue NS2B-NS3pro at IC(50) of 11.7 μM. The graded concentrations of PG-1 at nontoxic range were able to reduce viral replication significantly (P < 0.001) at 24, 48, and 72 hrs after viral infection. However, the percentage of inhibition was significantly (P < 0.01) higher at 24 hrs compared to 48 and 72 hrs. These data show promising therapeutic potential of PG-1 against dengue infection, hence it warrants further analysis and improvement of the peptide features as a prospective starting point for consideration in designing attractive dengue virus inhibitors.

Matched MeSH terms: Antimicrobial Cationic Peptides/pharmacology*
Purification and characterisation of antibacterial peptide-containing compound derived from palm kernel cake

Tan YN, Ayob MK, Wan Yaacob WA

Food Chem, 2013 Jan 1;136(1):279-84.
PMID: 23017424 DOI: 10.1016/j.foodchem.2012.08.012

Palm kernel cake (PKC), the most useful by-product resulted from palm kernel oil production. In this study, PKC-derived protein product was found suitable for use as an antimicrobial agent with potent antibacterial activity, particularly against Bacillus species, after enzymatic hydrolysis with alcalase. The hydrolysate was further purified by gel filtration chromatography. The purified fraction was found to have 14.63±0.70% (w/w) protein, a molecular mass of 2.4kDa and low hemolytic activity (<50% hemolysis of human erythrocytes at concentration of 1000μg/ml). The presence of lysine and the major component lauric acid derivative, as indicated by electrospray ionisation-mass spectrometry (ESI-MS) direct infusion and nuclear magnetic resonance (NMR) spectroscopy, may have contributed to the antibacterial effect of purified PKC fraction. This study suggests that the antibacterial PKC compound may be not a pure peptide but instead a peptide-containing compound high in lauric acid derivative.

Matched MeSH terms: Peptides/pharmacology
Molecular modelling, synthesis and biological evaluation of peptide inhibitors as anti-angiogenic agent targeting neuropilin-1 for anticancer application

Kamarulzaman EE, Vanderesse R, Gazzali AM, Barberi-Heyob M, Boura C, Frochot C, et al.

J Biomol Struct Dyn, 2017 Jan;35(1):26-45.
PMID: 26766582 DOI: 10.1080/07391102.2015.1131196

Vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1 (NRP-1) are important targets of many pro-angiogenic factors. In this study, nine peptides were synthesized and evaluated for their molecular interaction with NRP-1 and compared to our previous peptide ATWLPPR. Docking study showed that the investigated peptides shared the same binding region as shown by tuftsin known to bind selectively to NRP-1. Four pentapeptides (DKPPR, DKPRR, TKPPR and TKPRR) and a hexapeptide CDKPRR demonstrated good inhibitory activity against NRP-1. In contrast, peptides having arginine residue at sites other than the C-terminus exhibited low activity towards NRP-1 and this is confirmed by their inability to displace the VEGF165 binding to NRP-1. Docking study also revealed that replacement of carboxyl to amide group at the C-terminal arginine of the peptide did not affect significantly the binding interaction to NRP-1. However, the molecular affinity study showed that these peptides have marked reduction in the activity against NRP-1. Pentapeptides having C-terminal arginine showed strong interaction and good inhibitory activity with NRP thus may be a good template for anti-angiogenic targeting agent.

Matched MeSH terms: Peptides/pharmacology
Fulltext The endogenous antimicrobial cathelicidin LL37 induces platelet activation and augments thrombus formation

Salamah MF, Ravishankar D, Kodji X, Moraes LA, Williams HF, Vallance TM, et al.

Blood Adv, 2018 11 13;2(21):2973-2985.
PMID: 30413433 DOI: 10.1182/bloodadvances.2018021758

Platelet-associated complications including thrombosis, thrombocytopenia, and hemorrhage are commonly observed during various inflammatory diseases such as sepsis, inflammatory bowel disease, and psoriasis. Despite the reported evidence on numerous mechanisms/molecules that may contribute to the dysfunction of platelets, the primary mechanisms that underpin platelet-associated complications during inflammatory diseases are not fully established. Here, we report the discovery of formyl peptide receptor 2, FPR2/ALX, in platelets and its primary role in the development of platelet-associated complications via ligation with its ligand, LL37. LL37 acts as a powerful endogenous antimicrobial peptide, but it also regulates innate immune responses. We demonstrate the impact of LL37 in the modulation of platelet reactivity, hemostasis, and thrombosis. LL37 activates a range of platelet functions, enhances thrombus formation, and shortens the tail bleeding time in mice. By utilizing a pharmacological inhibitor and Fpr2/3 (an ortholog of human FPR2/ALX)-deficient mice, the functional dependence of LL37 on FPR2/ALX was determined. Because the level of LL37 is increased in numerous inflammatory diseases, these results point toward a critical role for LL37 and FPR2/ALX in the development of platelet-related complications in such diseases. Hence, a better understanding of the clinical relevance of LL37 and FPR2/ALX in diverse pathophysiological settings will pave the way for the development of improved therapeutic strategies for a range of thromboinflammatory diseases.

Matched MeSH terms: Antimicrobial Cationic Peptides/pharmacology*
Structure-informed separation of bioactive peptides

Acquah C, Chan YW, Pan S, Agyei D, Udenigwe CC

J Food Biochem, 2019 01;43(1):e12765.
PMID: 31353493 DOI: 10.1111/jfbc.12765

The application of proteomic and peptidomic technologies for food-derived bioactive peptides is an emerging field in food sciences. These technologies include the use of separation tools coupled to a high-resolution spectrometric and bioinformatic tools for prediction, identification, sequencing, and characterization of peptides. To a large extent, one-dimensional separation technologies have been extensively used as a continuous tool under different optimized conditions for the identification and analysis of food peptides. However, most one-dimensional separation technologies are fraught with significant bottlenecks such as insufficient sensitivity and specificity limits for complex samples. To address this limitation, separation systems based on orthogonal, multidimensional principles, which allow for the coupling of more than one analytical separation tool with different operational principles, provide a higher separation power than one-dimensional separation tools. This review describes the structure-informed separation and purification of protein hydrolyzates to obtain peptides with desirable bioactivities. PRACTICAL APPLICATIONS: Application of bioactive peptides in the formulation of functional foods, nutraceuticals, and therapeutic agents have increasingly gained scholarly and industrial attention. The bioactive peptides exist originally in protein sources and are only active after hydrolysis of the parent protein. Currently, several tools can be configured in one-dimensional or multidimensional systems for the separation and purification of protein hydrolyzates. The separations are informed by the structural properties such as the molecular weight, charge, hydrophobicity or hydrophilicity, and the solubility of peptides. This review provides a concise discussion on the commonly used analytical tools, their configurations, advantages and challenges in peptide separation. Emphasis is placed on how the structural properties of peptides assist in the separation and purification processes and the concomitant effect of the separation on peptide bioactivity.

Matched MeSH terms: Peptides/pharmacology*
Discovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides

Ahmad Nadzirin I, Chor ALT, Salleh AB, Rahman MBA, Tejo BA

Comput Biol Chem, 2021 Jun;92:107487.
PMID: 33957477 DOI: 10.1016/j.compbiolchem.2021.107487

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting about 0.24 % of the world population. Protein arginine deiminase type 4 (PAD4) is believed to be responsible for the occurrence of RA by catalyzing citrullination of proteins. The citrullinated proteins act as autoantigens by stimulating an immune response. Citrullinated α-enolase has been identified as one of the autoantigens for RA. Hence, α-enolase serves as a suitable template for design of potential peptide inhibitors against PAD4. The binding affinity of α-enolase-derived peptides and PAD4 was virtually determined using PatchDock and HADDOCK docking programs. Synthesis of the designed peptides was performed using a solid phase peptide synthesis method. The inhibitory potential of each peptide was determined experimentally by PAD4 inhibition assay and IC50 measurement. PAD4 assay data show that the N-P2 peptide is the most favourable substrate among all peptides. Further modification of N-P2 by changing the Arg residue to canavanine [P2 (Cav)] rendered it an inhibitor against PAD4 by reducing the PAD4 activity to 35 % with IC50 1.39 mM. We conclude that P2 (Cav) is a potential inhibitor against PAD4 and can serve as a starting point for the development of even more potent inhibitors.

Matched MeSH terms: Peptides/pharmacology*
Hepatitis B virus peptide inhibitors: solution structures and interactions with the viral capsid

Muhamad A, Ho KL, Rahman MB, Tejo BA, Uhrín D, Tan WS

Org Biomol Chem, 2015 Jul 28;13(28):7780-9.
PMID: 26100394 DOI: 10.1039/c5ob00449g

Hepatitis B virus (HBV) infection remains a health problem globally despite the availability of effective vaccines. In the assembly of the infectious virion, both the preS and S regions of the HBV large surface antigen (L-HBsAg) interact synergistically with the viral core antigen (HBcAg). Peptides preS and S based on the L-HBsAg were demonstrated as potential inhibitors to block the viral assembly. Therefore, the objectives of this study were to determine the solution structures of these peptides and study their interactions with HBcAg. The solution structures of these peptides were solved using (1)H, (13)C, and (15)N NMR spectroscopy. Peptide preS has several structured regions of β-turns at Ser7-Pro8-Pro9, Arg11-Thr12-Thr13 and Ser22-Thr23-Thr24 sequences whereas peptide S has only one structured region observed at Ser3-Asn4-His5. Both peptides contain bend-like structures surrounding the turn structures. Docking studies revealed that both peptides interacted with the immunodominant region of HBcAg located at the tip of the viral capsid spikes. Saturation Transfer Difference (STD) NMR experiments identified several aromatic residues in peptides preS and S that interact with HBcAg. This study provides insights into the contact regions of L-HBsAg and HBcAg at atomic resolution which can be used to design antiviral agents that inhibit HBV morphogenesis.

Matched MeSH terms: Peptides/pharmacology
Peptide inhibitors of Macrobrachium rosenbergii nodavirus

Thong QX, Wong CL, Ooi MK, Kueh CL, Ho KL, Alitheen NB, et al.

J Gen Virol, 2018 09;99(9):1227-1238.
PMID: 30041713 DOI: 10.1099/jgv.0.001116

Macrobrachium rosenbergii nodavirus (MrNv) causes white tail disease (WTD) in giant freshwater prawns, which leads to devastating economic losses in the aquaculture industry. Despite extensive research on MrNv, there is still no antiviral agent to treat WTD. Thus, the main aim of this study was to identify potential anti-MrNv molecules. A 12-mer phage-displayed peptide library was biopanned against the MrNv virus-like particle (VLP). After four rounds of biopanning, two dominant phages harbouring the amino acid sequences HTKQIPRHIYSA and VSRHQSWHPHDL were selected. An equilibrium binding assay in solution was performed to determine the relative dissociation constant (KDrel) of the interaction between the MrNv VLP and the selected fusion phages. Phage-HTKQIPRHIYSA has a KDrel value of 92.4±22.8 nM, and phage-VSRHQSWHPHDL has a KDrel value of 12.7±3.8 nM. An in-cell elisa was used to determine the inhibitory effect of the synthetic peptides towards the entry of MrNv VLP into Spodoptera frugiperda (Sf9) cells. Peptides HTKQIPRHIYSA and VSRHQSWHPHDL inhibited the entry of the MrNv VLP into Sf9 cells with IC50 values of 30.4±3.6 and 26.5±8.8 µM, respectively. Combination of both peptides showed a significantly higher inhibitory effect with an IC50 of 4.9±0.4 µM. An MTT assay revealed that the viability of MrNv-infected cells increased to about 97 % in the presence of both peptides. A real-time RT-PCR assay showed that simultaneous application of both peptides significantly reduced the number of MrNv per infected cell, from 97±9 to 11±4. These peptides are lead compounds which can be further developed into potent anti-MrNv agents.

Matched MeSH terms: Peptides/pharmacology*
Anticancer Properties of Asian Water Monitor Lizard (Varanus salvator), Python (Malayopython reticulatus) and Tortoise (Cuora kamaroma amboinensis)

Jeyamogan S, Khan NA, Sagathevan K, Siddiqui R

Anticancer Agents Med Chem, 2020;20(13):1558-1570.
PMID: 32364082 DOI: 10.2174/1871520620666200504103056

BACKGROUND: Cancer contributes to significant morbidity and mortality despite advances in treatment and supportive care. There is a need for the identification of effective anticancer agents. Reptiles such as tortoise, python, and water monitor lizards are exposed to heavy metals, tolerate high levels of radiation, feed on rotten/germ-infested feed, thrive in unsanitary habitat and yet have prolonged lifespans. Such species are rarely reported to develop cancer, suggesting the presence of anticancer molecules/mechanisms.
METHODS: Here, we tested effects from sera of Asian water monitor lizard (Varanus salvator), python (Malayopython reticulatus) and tortoise (Cuora kamaroma amboinensis) against cancer cells. Sera were collected and cytotoxicity assays were performed using prostate cancer cells (PC3), Henrietta Lacks cervical adenocarcinoma cells (HeLa) and human breast adenocarcinoma cells (MCF7), as well as human keratinized skin cells (Hacat), by measuring lactate dehydrogenase release as an indicator for cell death. Growth inhibition assays were performed to determine the effects on cancer cell proliferation. Liquid chromatography mass spectrometry was performed for molecular identification.
RESULTS: The findings revealed that reptilian sera, but not bovine serum, abolished viability of Hela, PC3 and MCF7 cells. Samples were subjected to liquid chromatography mass spectrometry, which detected 57 molecules from V. salvator, 81 molecules from Malayopython reticulatus and 33 molecules from C. kamaroma amboinensis and putatively identified 9 molecules from V. salvator, 20 molecules from Malayopython reticulatus and 9 molecules from C. kamaroma amboinensis when matched against METLIN database. Based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition, 123 potential Anticancer Peptides (ACPs) were identified from 883 peptides from V. salvator, 306 potential ACPs from 1074 peptides from Malayopython reticulatus and 235 potential ACPs from 885 peptides from C. kamaroma amboinensis.
CONCLUSION: To our knowledge, for the first time, we reported comprehensive analyses of selected reptiles' sera using liquid chromatography mass spectrometry, leading to the identification of potentially novel anticancer agents. We hope that the discovery of molecules from these animals will pave the way for the rational development of new anticancer agents.

Matched MeSH terms: Antimicrobial Cationic Peptides/pharmacology*
Anti-dengue virus serotype 2 activity and mode of action of a novel peptide

Chew MF, Tham HW, Rajik M, Sharifah SH

J Appl Microbiol, 2015 Oct;119(4):1170-80.
PMID: 26248692 DOI: 10.1111/jam.12921

To identify a novel antiviral peptide against dengue virus serotype 2 (DENV-2) by screening a phage display peptide library and to evaluate its in vitro antiviral activity and mode of action.

Matched MeSH terms: Peptides/pharmacology*
Epinecidin-1, a marine antifungal peptide, inhibits Botrytis cinerea and delays gray mold in postharvest peaches

Fan L, Wei Y, Chen Y, Jiang S, Xu F, Zhang C, et al.

Food Chem, 2023 Mar 01;403:134419.
PMID: 36191421 DOI: 10.1016/j.foodchem.2022.134419

This study investigatedthe mechanism of epinecidin-1 against Botrytis cinerea, in vitro, and its effectiveness at inhibiting gray mold on postharvest peach fruit. We found that in vitro, epinecidin-1 had significantly greater antifungal activity against B. cinerea than either clavanin-A or mytimycin, two other marine derived antimicrobial peptides that we tested. Its antifungal activity was heat-resistant (15 min at 40-100 °C) and tolerant to lower concentrations of cations (<100 mM Na+, K+; <10 mM Ca2+). Epinecidin-1 interacted directly with B. cinerea genomic DNA, and that in mycelia, epinecidin-1 exposure induced accumulation of intracellular ROS and increased the permeability of cell membranes resulting in leakage of nucleic acids and aberrant cell morphology. Meanwhile, 200 μM of epinecidin-1 had a significant inhibitory effect on gray mold injected into peach fruit. These results suggested that epinecidin-1 showed promise as a potential method for controlling postharvest gray mold in peaches.

Matched MeSH terms: Peptides/pharmacology
Fulltext Prediction of antimicrobial peptides based on sequence alignment and support vector machine-pairwise algorithm utilizing LZ-complexity

Ng XY, Rosdi BA, Shahrudin S

Biomed Res Int, 2015;2015:212715.
PMID: 25802839 DOI: 10.1155/2015/212715

This study concerns an attempt to establish a new method for predicting antimicrobial peptides (AMPs) which are important to the immune system. Recently, researchers are interested in designing alternative drugs based on AMPs because they have found that a large number of bacterial strains have become resistant to available antibiotics. However, researchers have encountered obstacles in the AMPs designing process as experiments to extract AMPs from protein sequences are costly and require a long set-up time. Therefore, a computational tool for AMPs prediction is needed to resolve this problem. In this study, an integrated algorithm is newly introduced to predict AMPs by integrating sequence alignment and support vector machine- (SVM-) LZ complexity pairwise algorithm. It was observed that, when all sequences in the training set are used, the sensitivity of the proposed algorithm is 95.28% in jackknife test and 87.59% in independent test, while the sensitivity obtained for jackknife test and independent test is 88.74% and 78.70%, respectively, when only the sequences that has less than 70% similarity are used. Applying the proposed algorithm may allow researchers to effectively predict AMPs from unknown protein peptide sequences with higher sensitivity.

Matched MeSH terms: Peptides/pharmacology*
Effects of macrophage colony-stimulating factor on microglial responses to lipopolysaccharide and beta amyloid

Vidyadaran S, Ooi YY, Subramaiam H, Badiei A, Abdullah M, Ramasamy R, et al.

Cell Immunol, 2009;259(1):105-10.
PMID: 19577228 DOI: 10.1016/j.cellimm.2009.06.005

A challenge for studies involving microglia cultures is obtaining sufficient cells for downstream experiments. Macrophage colony-stimulating factor (M-CSF) has been used to improve yield of microglia in culture. However, the effects of M-CSF on activation profiles of microglia cultures are still unclear. Microglia activation is characterised by upregulation of co-stimulatory molecules and an inflammatory phenotype. The aim of this study is to demonstrate whether M-CSF supplementation alters microglial responses in resting and activated conditions. Microglia derived from mixed glia cultures and the BV-2 microglia cell line were cultivated with/without M-CSF and activated with lipopolysaccharide (LPS) and beta amyloid (Abeta). We show M-CSF expands primary microglia without affecting microglial responses to LPS and Abeta, as shown by the comparable expression of MHC class II and CD40 to microglia grown without this growth factor. M-CSF supplementation in BV-2 cells had no effect on nitric oxide (NO) production. Therefore, M-CSF can be considered for improving microglia yield in culture without introducing activation artefacts.

Matched MeSH terms: Amyloid beta-Peptides/pharmacology*
Fulltext Intracellular Targeting Mechanisms by Antimicrobial Peptides

Le CF, Fang CM, Sekaran SD

Antimicrob Agents Chemother, 2017 04;61(4).
PMID: 28167546 DOI: 10.1128/AAC.02340-16

Antimicrobial peptides (AMPs) are expressed in various living organisms as first-line host defenses against potential harmful encounters in their surroundings. AMPs are short polycationic peptides exhibiting various antimicrobial activities. The principal antibacterial activity is attributed to the membrane-lytic mechanism which directly interferes with the integrity of the bacterial cell membrane and cell wall. In addition, a number of AMPs form a transmembrane channel in the membrane by self-aggregation or polymerization, leading to cytoplasm leakage and cell death. However, an increasing body of evidence has demonstrated that AMPs are able to exert intracellular inhibitory activities as the primary or supportive mechanisms to achieve efficient killing. In this review, we focus on the major intracellular targeting activities reported in AMPs, which include nucleic acids and protein biosynthesis and protein-folding, protease, cell division, cell wall biosynthesis, and lipopolysaccharide inhibition. These multifunctional AMPs could serve as the potential lead peptides for the future development of novel antibacterial agents with improved therapeutic profiles.

Matched MeSH terms: Antimicrobial Cationic Peptides/pharmacology*

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