Refined homology model of cytochrome bcc complex B subunit for virtual screening of potential anti-tuberculosis agents

Abstract

Cytochrome bcc complex is important for ATP synthesis and cellular activity, as a crucial step in the terminal reduction of oxygen in aerobic electron transport chains. The b subunit of cytochrome bcc complex (QcrB) has been reported as a promising anti-tuberculosis target, with many novel anti-tuberculosis scaffolds reported. However, the 3D structure of mycobacterium tuberculosis (M. tuberculosis) QcrB has not been released, making it hard to understand the interactions between QcrB and its inhibitors as well as to develop novel anti-tuberculosis scaffolds. Herein we built the optimal homology model of M. tuberculosis QcrB using the M. smegmatis QcrB structure as template, which was refined through all-atom molecular dynamics simulation. Then, the binding modes of known inhibitors were predicted through molecular docking method, along with molecular dynamics simulation and binding free energy calculation to verify the accuracy of docking results and stability of the protein-inhibitor complexes. The informative key residues within QcrB site enabled us to perform structure-based virtual library screening to obtain potential M. tuberculosis QcrB inhibitors, which were validated through molecular dynamics simulation and MM-GBSA calculation and analyzed through pharmacokinetic properties prediction. Our research would provide a deeper insight into the interactions between M. tuberculosis QcrB and its inhibitors, which boosts to develop novel therapy against tuberculosis.

Communicated by Ramaswamy H. Sarma     

Synthesis,molecular docking,binding free energy calculation and molecular dynamics simulation studies of benzothiazol-2-ylcarbamodithioates as Staphylococcus aureus MurD inhibitors

Abstract

A new series of benzothiazol-2-ylcarbamodithioate functional compounds 5a-f has been designed, synthesized and characterized by spectral data. These compounds were screened for their in vitro antibacterial activity against strains of Staphylococcus aureus (NCIM 5021, NCIM 5022 and methicillin-resistant isolate 43300), Bacillus subtilis (NCIM 2545), Escherichia coli (NCIM 2567), Klebsiella pneumoniae (NCIM 2706) and Psudomonas aeruginosa (NCIM 2036). Compounds 5a and 5d exhibited significant activity against all the tested bacterial strains. Specifically, compounds 5a and 5d showed potent activity against K. pneumoniae (NCIM 2706), while compound 5a also displayed potent activity against S. aureus (NCIM 5021). Compound 5d showed minimum IC₅₀ value of 13.37?μM against S. aureus MurD enzyme. Further, the binding interactions of compounds 5a-f in the catalytic pocket have been investigated using the extra-precision molecular docking and binding free energy calculation by MM-GBSA approach. A 30?ns molecular dynamics simulation of 5d/modeled S. aureus MurD enzyme was performed to determine the stability of the predicted binding conformation.     

The identification of novel,high affinity AQP9 inhibitors in an intracellular binding site

Abstract

Background: The involvement of aquaporin (AQP) water and small solute channels in the etiology of several diseases, including cancer, neuromyelitis optica and body fluid imbalance disorders, has been suggested previously. Furthermore, results obtained in a mouse model suggested that AQP9 function contributes to hyperglycemia in type-2 diabetes. In addition, the physiological role of several AQP family members remains poorly understood. Small molecule inhibitors of AQPs are therefore desirable to further study AQP physiological and pathophysiological functions. Methods: The binding of recently established AQP9 inhibitors to a homology model of AQP9 was investigated by molecular dynamics simulations and molecular docking. Putative inhibitor binding sites identified with this procedure were modified by site-directed mutagenesis. Active compounds were measured in a mammalian cell water permeability assay of mutated AQP9 isoforms and tested for changes in inhibitory effects. Controls: Three independent cell lines were established for each mutated AQP9 isoform and functionality of mutant isoforms was established. Principal findings: We have identified putative binding sites of recently established AQP9 inhibitors. This information facilitated successful identification of novel AQP9 inhibitors with low micromolar IC50 values in a cell based assay by in silico screening of a compound library targeting specifically this binding site. Significance: We have established a successful strategy for AQP small molecule inhibitor identification. AQP inhibitors may be relevant as experimental tools, to enhance our understanding of AQP function, and in the treatment of various diseases.     

A profound computational study to prioritize the natural compound inhibitors against the P. falciparum orotidine-5-monophosphate decarboxylase enzyme

Abstract

In the current contribution, a multicomplex-based pharmacophore modeling approach was employed on the structural proteome of Plasmodium falciparum orotidine-5-monophosphate decarboxylase enzyme (PfOMPDC). Among the constructed pharmacophore models, the representative hypotheses were selected as the primary filter to screen the molecules with the complementary features responsible for showing inhibition. Thereafter, auxiliary evaluations were performed on the screened candidates via drug-likeness and molecular docking studies. Subsequently, the stability of the docked protein-ligand complexes was scrutinized by employing molecular dynamics simulations and molecular mechanics-Poisson Boltzmann surface area based free binding energy calculations. The stability the docked candidates was compared with the highly active crystallized inhibitor (3S9Y-FNU) to seek more potential candidates. All the docked molecules displayed stable dynamic behavior and high binding free energy in comparison to 3S9Y-FNU. The employed workflow resulted in the retrieval of five drug-like candidates with diverse scaffolds that may show inhibitory activity against PfOMPDC and could be further used as the novel scaffold to develop novel antimalarials.

Communicated by Ramaswamy H. Sarma     

Molecular dynamics analysis of the effects of GTP,GDP and benzimidazole derivative on structural dynamics of a cell division protein FtsZ from Mycobacterium tuberculosis

Abstract

The prevailing multi-drug resistance in Mycobacterium tuberculosis continues to remain one of the main challenges to combat tuberculosis. Hence, it becomes imperative to focus on novel drug targets. Filamenting temperature-sensitive mutant Z (FtsZ) is an essential cell division protein, a eukaryotic tubulin homologue and a promising drug target. During cytokinesis, FtsZ polymerises in the presence of GTP to form Z-ring and recruits other proteins at this site that eventually lead to the formation of daughter cells. Benzimidazoles were experimentally shown to inhibit Mtb-FtsZ, with one of the benzimidazole derivatives, M1, being reported to have the minimum inhibitory concentration (MIC) value of 3.13 µg/mL. In the present study, mechanism of destabilisation of FtsZ in the presence of M1 was computationally investigated in the presence of its substrate GTP/GDP employing molecular dynamics (MD) simulation analysis, principal component analysis (PCA), molecular mechanics combined with the generalised Born and surface area continuum salvation (MM-GBSA) and density functional theory (DFT). From the analyses, it is proposed that binding of M1 in the inter-domain cleft induces structural changes in the GTP-binding region that affect GTP binding, thus switching the preference of this protein towards depolymerised state and eventually inhibiting the cell division. Hence, this study provides mechanistic insights into the design of novel benzimidazole inhibitors against Mtb-FtsZ.

Communicated by Ramaswamy H. Sarma     

Communication of γ Phage Lysin plyG Enzymes Binding toward SrtA for Inhibition of Bacillus Anthracis: Protein–Protein Interaction and Molecular Dynamics Study

Abstract

Bacillus anthracis is a pathogenic, Gram-positive bacterium which chiefly affects the livestock of animals and humans through acute disease anthrax. All around the globe this bio-threat organism damages millions of lives in every year and also most of the drugs were not responding properly in inhibition against this diseased pathogen. In recent development, phage therapy is considered as alternative solution to treat this serious infectious disease. In this study, we elucidated the binding of γ phage lysin plyG enzymes toward the SrtA along with its activator peptide LPXTG. Through protein–protein docking and molecular dynamics simulation studies, we showed the distinguished structure complementarity of SrtA and plyG complex. Especially, MD simulation relates strong and stable interaction occurs between the protein complex structures. These results suggest that additional experimental studies on our approach will lead to availability of better inhibitor against the SrtA.     

Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain

Abstract

Glutathione (GU), an endogenous antioxidant tripeptide, is frequently transferred in the human brain through N-methyl-d-aspartate receptor (NMDAR), profusely expressed at the blood–brain barrier (BBB) junction. GU, also modifies the characteristics of tight junction proteins (occludin and claudin) at the site of BBB by depolarizing the enzyme, protein tyrosine phosphatase that manifests its usefulness for passive delivery of nanocarriers to the brain. GU, thus, represents itself as an ideal ligand for the surface decoration of nanocarriers to successfully administer them across the brain via receptor-mediated drug delivery pathway. Hence, we have employed here, in-silico approaches to identify the potential GU-like molecules, as appropriate ligand(s) for surface engineering of nanoconstruct with the purpose of attaining targeted drug delivery to the brain. Structure-based virtual screening methods was used to filter PubChem database for the identification of bioactive compounds with >95% structure similarity with GU. We have further screened the compounds against NMDAR using molecular docking approach. Top hits were selected based on their high binding affinities and selectivity towards NMDAR, and their binding pattern was analysed in detail. Finally, all atom molecular dynamics simulation for 100?ns was carried out on free NMDAR and in-presence of the selected GU-like compound, gamma-l-glutamyl-l-cysteine to evaluate complex stability and structural dynamics. In conclusion, gamma-l-glutamyl-l-cysteine may act as potential binding partner of NMDAR which can further be evaluated in drug delivery system to brain across the BBB.

Communicated by Ramaswamy H. Sarma     

In vitro,fluorescence-quenching and computational studies on the interaction between lipoxygenase and 5-hydroxy-3′,4′,7-trimethoxyflavone from Lippia nodiflora L.

Abstract

Lippia nodiflora L. is extensively used in traditional medicine for several medicinal purposes, including their use in inflammatory disorders. In this study, the folk use of L. nodiflora was validated using the isolated natural compound, 5-hydroxy-3′,4′,7-trimethoxyflavone (HTMF) by in vitro, fluorescence spectroscopic and molecular modeling studies with lipoxygenase (LOX), because LOX plays an essential role in inflammatory responses. In this perspective, the methanol extract and HTMF are shown to demonstrate prominent inhibitory activity against soybean lipoxygenase, with an IC₅₀ value of 21.12 and 23.97?µg/ml, respectively. The data obtained from the spectroscopic method revealed that the quenching of intrinsic fluorescence of LOX is produced as a result of the complex formation of LOX–HTMF. The binding mode analysis of HTMF within the LOX enzyme suggested that hydrogen bond formation, hydrophobic interaction and π–π stacking could account for the binding of HTMF. Molecular dynamics results indicated the interaction of HTMF with LOX and the stability of ligand–enzyme complex was maintained throughout the simulation. The computational results are reliable with experimental facts and provided a good representation for understanding the binding mode of HTMF inside the active site of lipoxygenase enzyme.     

Insights into the Substrate Specificity of a Thioesterase Rv0098 of Mycobacterium Tuberculosis through X-ray Crystallographic and Molecular Dynamics Studies

Abstract

The crystal structure of Rv0098, a long-chain fatty acyl-CoA thioesterase from Mycobacterium tuberculosis with bound dodecanoic acid at the active site provided insights into the mode of substrate binding but did not reveal the structural basis of substrate specificities of varying chain length. Molecular dynamics studies demonstrated that certain residues of the substrate binding tunnel are flexible and thus modulate the length of the tunnel. The flexibility of the loop at the base of the tunnel was also found to be important for determining the length of the tunnel for accommodating appropriate substrates. A combination of crystallographic and molecular dynamics studies thus explained the structural basis of accommodating long chain substrates by Rv0098 of M. tuberculosis.     

Synthesis and in vitro characterization of oxytocin receptor targeted PEGylated immunoliposomes for drug delivery to the uterus

Abstract

Targeted delivery of therapeutics to the uterus is an important goal in the treatment of obstetric complications, such as preterm labour, postpartum hemorrhage, and dysfunctional labour. Current treatment for these obstetric complications is challenging, as there are limited effective and safe therapeutic options available. We have developed a targeted drug delivery system for the uterus by conjugating anti-oxytocin receptor (OTR) antibodies to the surface of PEGylated liposomes (OTR-PEG-ILs). The functionality of the OTR-PEG-ILs has previously been evaluated on human and murine myometrial tissues as well as in vivo in a murine model of preterm labour. The aim of this study was to report the pharmaceutical synthesis and characterization of the OTR-PEG-ILs and investigate their specific cellular interaction with OTR-expressing myometrial cells in vitro. Immunoliposomes composed of 1,2-distearoyl-sn-glycero-2-phosphocholine (DSPC) and cholesterol were prepared using an optimized method for the coupling of low concentrations of antibody to liposomes. The liposomes were characterized for particle size, antibody conjugation, drug encapsulation, liposome stability, specificity of binding, cellular internalization, mechanistic pathway of cellular uptake, and cellular toxicity. Cellular association studies demonstrated specific binding of OTR-PEG-ILs to OTRs and significant cellular uptake following binding. Evaluation of the mechanistic pathway of cellular uptake indicated that they undergo internalization through both clathrin- and caveolin-mediated mechanisms. Furthermore, cellular toxicity studies have shown no significant effect of OTR-PEG-ILs or the endocytotic inhibitors on cell viability. This study further supports oxytocin receptors as a novel pharmaceutical target for drug delivery to the uterus.     

Molecular insights of benzodipyrazole as CDK2 inhibitors: combined molecular docking,molecular dynamics,and 3D QSAR studies

Abstract

Benzodipyrazoles have been previously evaluated for their in vitro CDK2 inhibitory activity. In the current investigation, we identified a six-feature common pharmacophore model (AADDRR.33) which is predicted to be responsible for CDK2 inhibition. An efficient 3D QSAR (r^2?=?0.98 and q^2?=?0.82) model was also constructed by employing PLS regression analysis. From the molecular docking studies, we examined the binding patterns of compound 7aa with the target protein and also calculated the binding energy using MM-GBSA calculations. Three hydrogen bonds with Lys 33, Glu 81, and Leu 83 are conserved even after 1000?ps run in a molecular dynamics simulation. We identified the slight displacement in bond lengths and the conformational changes occurred during the dynamics. The results also elucidated the protein residue–ligand interaction fractions which clearly explained the involvement of non-H-bond interactions.     

In silico trial to test COVID-19 candidate vaccines: a case study with UISS platform

Background

In 2018, about 10 million people were found infected by tuberculosis, with approximately 1.2 million deaths worldwide. Despite these numbers have been relatively stable in recent years, tuberculosis is still considered one of the top 10 deadliest diseases worldwide. Over the years, Mycobacterium tuberculosis has developed a form of resistance to first-line tuberculosis treatments, specifically to isoniazid, leading to multi-drug-resistant tuberculosis. In this context, the EU and Indian DBT funded project STriTuVaD—In Silico Trial for Tuberculosis Vaccine Development—is supporting the identification of new interventional strategies against tuberculosis thanks to the use of Universal Immune System Simulator (UISS), a computational framework capable of predicting the immunity induced by specific drugs such as therapeutic vaccines and antibiotics.

Results

Here, we present how UISS accurately simulates tuberculosis dynamics and its interaction within the immune system, and how it predicts the efficacy of the combined action of isoniazid and RUTI vaccine in a specific digital population cohort. Specifically, we simulated two groups of 100 digital patients. The first group was treated with isoniazid only, while the second one was treated with the combination of RUTI vaccine and isoniazid, according to the dosage strategy described in the clinical trial design. UISS-TB shows to be in good agreement with clinical trial results suggesting that RUTI vaccine may favor a partial recover of infected lung tissue.

Conclusions

In silico trials innovations represent a powerful pipeline for the prediction of the effects of specific therapeutic strategies and related clinical outcomes. Here, we present a further step in UISS framework implementation. Specifically, we found that the simulated mechanism of action of RUTI and INH are in good alignment with the results coming from past clinical phase IIa trials.

     

Structure-based screening and molecular dynamics simulations offer novel natural compounds as potential inhibitors of Mycobacterium tuberculosis isocitrate lyase

Mycobacterium tuberculosis is the etiological agent of tuberculosis in humans and is responsible for more than two million deaths annually. M. tuberculosis isocitrate lyase (MtbICL) catalyzes the first step in the glyoxylate cycle, plays a pivotal role in the persistence of M. tuberculosis, which acts as a potential target for an anti-tubercular drug. To identify the potential anti-tuberculosis compound, we conducted a structure-based virtual screening of natural compounds from the ZINC database (n = 1,67,748) against the MtbICL structure. The ligands were docked against MtbICL in three sequential docking modes that resulted in 340 ligands having better docking score. These compounds were evaluated for Lipinski and ADMET prediction, and 27 compounds were found to fit well with re-docking studies. After refinement by molecular docking and drug-likeness analyses, three potential inhibitors (ZINC1306071, ZINC2111081, and ZINC2134917) were identified. These three ligands and the reference compounds were further subjected to molecular dynamics simulation and binding energy analyses to compare the dynamic structure of protein after ligand binding and the stability of the MtbICL and bound complexes. The binding free energy analyses were calculated to validate and capture the intermolecular interactions. The results suggested that the three compounds had a negative binding energy with ?96.462, ?143.549, and ?122.526 kJ mol^?1 for compounds with IDs ZINC1306071, ZINC2111081, and ZINC2134917, respectively. These lead compounds displayed substantial pharmacological and structural properties to be drug candidates. We concluded that ZINC2111081 has a great potential to inhibit MtbICL and would add to the drug discovery process against tuberculosis.     

Combined pharmacophore modeling, 3D-QSAR and docking studies to identify novel HDAC inhibitors using drug repurposing

Abstract

Histone deacetylases (HDACs), a critical family of epigenetic enzymes, has emerged as a promising target for antitumor drugs. Here, we describe our protocol of virtual screening in identification of novel potential HDAC inhibitors through pharmacophore modeling, 3D-QSAR, molecular docking and molecular dynamics (MD) simulation. Considering the limitation of current virtual screening works, drug repurposing strategy was applied to discover druggable HDAC inhibitor. The ligand-based pharmacophore and 3D-QSAR models were established, and their reliability was validated by different methods. Then, the DrugBank database was screened, followed by molecular docking. MD simulation (100?ns) was performed to further study the stability of ligand binding modes. Finally, results indicated the hit DB03889 with high in silico inhibitory potency was suitable for further experimental analysis.

Communicated by Ramaswamy H. Sarma     

Folding profiles of antimicrobial scorpion venom-derived peptides on hydrophobic surfaces: a molecular dynamics study

Abstract

Most helical antimicrobial peptides (AMPs) are usually unfolded in aqueous solution; however they acquire their secondary structure in the presence of a hydrophobic environment such as lipid membranes. Being the biological membranes the main target of many AMPs it is necessary to understand their way of action. Pandinin 2 (Pin2) is an alpha-helical AMP isolated from the venom of the African scorpion Pandinus imperator which shows high antimicrobial activity against Gram-positive bacteria and it is less active against Gram-negative bacteria, nevertheless, it has strong hemolytic activity. Its chemically synthesized Pin2GVG analog has low hemolytic activity while keeping its antimicrobial activity. With the aim of exploring the partition and subsequent folding of these peptides, in this work we report the results of extensive molecular dynamics simulations of Pin2 and Pin2GVG peptides in the presence of 2 hydrophobic environments such as dodecyl-phosphocholine (DPC) micelle and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocoline (POPC) membrane. Our results indicate that Pin2 folds in DPC with a 79% of alpha-helical content, which is in agreement with the experimental results, while in POPC it has 62.5% of alpha-helical content. On the other hand, Pin2GVG presents a higher percentage of alpha-helical structure in POPC and a smaller content in DPC when compared with Pin2. These results can help to better choose the starting structures in future molecular dynamics simulations of AMPs, because these peptides can adopt slightly different conformations depending on the hydrophobic environment.

Communicated by Ramaswamy H. Sarma     

Probing the acting mode and advantages of RMC-4550 as an Src-homology 2 domain-containing protein tyrosine phosphatase (SHP2) inhibitor at molecular level through molecular docking and molecular dynamics

Abstract

The over-activation of Ras/mitogen-activated protein kinase (MAPK) signaling pathway associated with a variety of cancers is usually related with abnormal activation of Src-homology 2 domain-containing protein tyrosine phosphatase (SHP2). For this purpose, SHP2 has attracted extensive interest as a potential target for cancer treatment. RMC-4550, as a newly developed selective inhibitor of SHP2, possesses an overwhelming advantage over the previous generation inhibitor SHP099 in terms of in vitro activity. However, the binding mode of SHP2 with RMC-4550 and the reason for the high efficiency of RMC-4550 as SHP2 inhibitor at molecular level are still unclear. Therefore, in this study, the binding mode of RMC-4550 with SHP2 and the superiorities of RMC-4550 as inhibitor at binding affinity and dynamic interactive behavior with SHP2 were probed by molecular docking and molecular dynamics (MD) simulations. By comparing the results of molecular docking, it was found that SHP2 formed more tight interaction with RMC-4550 than that with SHP099. Subsequently, a series of post-dynamic analyses on three simulation trajectories (SHP2^WT, SHP2^SHP099 and SHP2^RMC-4550) were performed and found that the SHP2 protein bound with RMC-4550 maintained a firmer interaction between N-Src-homology 2 (N-SH2) and PTP domain throughout the MD simulation, leading to a more stable protein conformation. The finding here provides new clues for the design of SHP2 inhibitor against the over-activation of Ras/MAPK pathway.

Communicated by Ramaswamy H. Sarma     

Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox: part II

Abstract

Acknowledging the importance of studies toward the development of measures against terrorism and bioterrorism, this study aims to contribute to the design of new prototypes of potential drugs against smallpox. Based on a former study, nine synthetic feasible prototypes of selective inhibitors for thymidylate kinase from Variola virus (VarTMPK) were designed and submitted to molecular docking, molecular dynamics simulations and binding energy calculations. The compounds are simplifications of two more complex scaffolds, with a guanine connected to an amide or alcohol through a spacer containing ether and/or amide groups, formerly suggested as promising for the design of selective inhibitors of VarTMPK. Our study showed that, despite the structural simplifications, the compounds presented effective energy values in interactions with VarTMPK and HssTMPK and that the guanine could be replaced by a simpler imidazole ring linked to a –NH₂ group, without compromising the affinity for VarTMPK. It was also observed that a positive charge in the imidazole ring is important for the selectivity toward VarTMPK and that an amide group in the spacer does not contribute to selectivity. Finally, prototype 3 was pointed as the most promising to be synthesized and experimentally evaluated.

Communicated by Ramaswamy H. Sarma     

Design,synthesis and molecular modelling studies of some pyrazole derivatives as carbonic anhydrase inhibitors

Abstract

In this study, newly synthesised compounds 6, 8, 10 and other compounds (1–5, 7 and 9) and their inhibitory properties against the human isoforms hCA I and hCA II were reported for the first time. Compounds 1–10 showed effective inhibition profiles with K _I values in the range of 5.13–16.9?nM for hCA I and of 11.77–67.39?nM against hCA II, respectively. Molecular docking studies were also performed with Glide XP to get insight into the inhibitory activity and to evaluate the binding modes of the synthesised compounds to hCA I and II. More rigorous binding energy calculations using MM-GBSA protocol which agreed well with observed activities were then performed to improve the docking scores. Results of in silico calculations showed that all compounds obey drug likeness properties. The new compounds reported here might be promising lead compounds for the development of new potent inhibitors as alternatives to classical hCA inhibitors.     

Experimental and theoretical investigations of Dy(III) complex with 2,2′-bipyridine ligand: DNA and BSA interactions and antimicrobial activity study

Abstract

In this study, the interactions of a novel metal complex [Dy(bpy)₂Cl₃.OH₂] (bpy is 2,2'-bipyridine) with fish salmon DNA (FS-DNA) and bovine serum albumin (BSA) were investigated by experimental and theoretical methods. All results suggested significant binding between the Dy(III) complex with FS-DNA and BSA. The binding constants (K_b), Stern-Volmer quenching constants (K_SV) of Dy(III)-complex with FS-DNA and BSA at various temperatures as well as thermodynamic parameters using Van’t Hoff equation were obtained. The experimental results from absorption, ionic strength, iodide ion quenching, ethidium bromide (EtBr) quenching studies and positive ΔH? and ΔS? suggested that hydrophobic groove-binding mode played a predominant role in the binding of Dy(III)-complex with FS-DNA. Indeed, the molecular docking results for DNA-binding were in agreement with experimental data. Besides, the results found from experimental and molecular modeling indicated that the Dy(III)-complex bound to BSA via Van der Waals interactions. Moreover, the results of competitive tests by phenylbutazone, ibuprofen, and hemin (as a site-I, site-II and site-III markers, respectively) considered that the site-III of BSA is the most possible binding site for Dy(III)-complex. In addition, Dy(III) complex was concurrently screened for its antimicrobial activities. The presented data provide a promising platform for the development of novel metal complexes that target nucleic acids and proteins with antimicrobial activity.

Communicated by Ramaswamy H. Sarma