Combinatorial Effect of Temozolomide and Naringenin in Human Glioblastoma Multiforme Cell Lines.

Glioblastoma multiforme (GBM) is a grade IV, lethal, and the most common type of brain tumor. GBM can acquire resistance to temozolomide (TMZ) recommended for its treatment. Naringenin (NAG), a flavonoid generally found in grapefruit, has antioxidant, anti-proliferative, and anti-inflammatory properties. It has been reported that phytochemicals can reduce resistance and improve the efficacy of a chemo-resistant drug. The combinatorial effect of TMZ and NAG on cell proliferation was evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay, and the apoptosis in the U87MG and LN229 GBM cells were evaluated by change in fluorescence intensity. The effect of NAG and TMZ on anchorage-independent single-cell colony formation and cell migration was investigated. NAG and TMZ demonstrated enhanced cytotoxic effects on U87MG and LN229 cell lines. The combination index value being less than one indicated the synergistic action of the two drugs in restricting the growth of the cells. The NAG and TMZ together resulted in higher fluorescence intensity as compared to the alone drug. Further, the study showed a marked reduction in the migration of the cells and the formation of a single cell colony.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1952438.

In vitro & in vivo evaluations of PLGA nanoparticle based combinatorial drug therapy for baclofen and lamotrigine for neuropathic pain management.

AIM: Baclofen and Lamotrigine via PLGA nanoparticles were developed for nose-to-brain delivery for the treatment of Neuropathic pain. METHODS: Nanoparticles were prepared using the modified nano-precipitation method. The prepared NPs were characterised and further in vitro and in vivo studies were performed. RESULTS: The Bcf-Ltg-PLGA-NPs were ∼177.7 nm with >75%(w/w) drugs encapsulated. In vitro dissolution studies suggested zero-order release profiles following the Korsmeyer-Peppas model. In vitro cytotoxicity and staining studies on mammalian cells showed dose dependant cytotoxicity where nanoparticles were significantly less toxic (>95% cell-viability). ELISA studies on RAW-macrophages showed Bcf-Ltg-PLGA-NPs as a potential pro-inflammatory-cytokines inhibitor. In vivo gamma-scintigraphy studies on rats showed intra-nasal administration of 99mTc-Bcf-Ltg-PLGA-NPs showed Cmax 3.6%/g at Tmax = 1.5h with DTE% as 191.23% and DTP% = 38.61% in brain. Pharmacodynamics evaluations on C57BL/6J mice showed a significant reduction in licks/bites during inflammation-induced phase II pain. CONCLUSION: The findings concluded that the combination of these drugs into a single nanoparticle-based formulation has potential for pain management.

Baclofen and Lamotrigine loaded PLGA nanoparticles were prepared with a size of 177.7nm, PDI 0.057 and Zeta Potential −15.8 mVIn vitro cell lines based studies showed dose dependant cytotoxicity and Bcf-Ltg-PLGA-NPs were found to be pro-inflammatory cytokines inhibitorsIn vivo Pharmacokinetic studies showed C_max 3.6%/g at T_max = 1.5 h with Drug Targeting Efficiency 191.23% and Drug Target Organ Transport 38.61% in the brain for prepared nanoparticlesIn vivo pharmacodynamics studies showed a significant reduction in licks/bites during inflammation-induced phase II pain.

Synergistic antibacterial and anti-biofilm activity of nisin like bacteriocin with curcumin and cinnamaldehyde against ESBL and MBL producing clinical strains.

Bacteriocins are small peptides that can inhibit the growth of a diverse range of microbes. There is a need to identify bacteriocins that are effective against biofilms of resistant clinical strains. The present study focussed on the efficacy of purified nisin like bacteriocin-GAM217 against extended spectrum ß-lactamase (ESBL) and metallo-beta-lactamase (MBL) producing clinical strains. Bacteriocin-GAM217 when combined with curcumin and cinnamaldehyde, synergistically enhanced antibacterial activity against planktonic and biofilm cultures of Staphylococcus epidermidis and Escherichia coli. Bacteriocin-GAM217 and phytochemical combinations inhibited biofilm formation by >80%, and disrupted the biofilm for selected ESBL and MBL producing clinical strains. The anti-adhesion assay showed that these combinatorial compounds significantly lowered the attachment of bacteria to Vero cells and that they elicited membrane permeability and rapid killing as viewed by confocal microscopy. This study demonstrates that bacteriocin-GAM217 in combination with phytochemicals can be a potential anti-biofilm agent and thus has potential for biomedical applications.

Antibacterial Activity, Cytotoxicity, and the Mechanism of Action of Bacteriocin from Bacillus subtilis GAS101.

OBJECTIVE: The aim of this study was to purify and characterize bacteriocin from the soil isolate Bacillus subtilis GAS101, and to determine its antimicrobial as well as antibiofilm potential. The purified bacteriocin was further analyzed and evaluated for mammalian cell cytotoxicity and the possible mode of action. MATERIAL AND METHODS: Bacteriocin from B. subtilis GAS101 (an animal husbandry soil isolate) was partially purified and checked for antimicrobial and antibiofilm activity against gram-positive and gram-negative bacteria. The molecular weight of bacteriocin was determined using tricine SDS-PAGE gel. The stability of bacteriocin was investigated at various temperatures and pH levels, and its sensitivity towards 8 enzymes and 6 chemicals was determined. Cytotoxicity analysis was performed on a Vero cell line by a tetrazolium dye-based assay. Scanning electron microscopy (SEM) of bacteriocin-treated bacteria was carried out to determine the possible mode of action. RESULTS: Bacteriocin from B. subtilis GAS101 was a potential inhibitor of both the indicator organisms (Staphylococcus epidermidis and Escherichia coli), and had a molecular weight of approximately 6.5 kDa. An in situ gel assay showed a zone of inhibition corresponding to the estimated protein band size. Bacteriocin was stable and showed antibacterial activity in broad ranges of temperature (30-121°C) and pH (2-12). It was sensitive to 4 proteolytic enzymes, which indicated its proteinaceous nature. Bacteriocin showed > 70% cell viability on the mammalian Vero cell line. SEM depicted that the bacteriocin was able to disrupt the bacterial cell membrane as its probable mode of action. CONCLUSION: Thermostable and pH-tolerant bacteriocin from B. subtilis GAS101, of about 6.5 kDa, showed broad-spectrum antimicrobial and antibiofilm activity.

Intravaginal Delivery of Polyphenon 60 and Curcumin Nanoemulsion Gel.

Polyphenon 60 (P60) and curcumin (CUR) were loaded in a single nanoemulsion system and their combined antibacterial action was studied against uropathogenic Escherichia coli. To enhance availability at target organs and to inhibit enzymatic degradation in gastro intestinal tract, vaginal route of administration was explored. P60 + CUR nanoemulsion (NE) was formulated by ultra-sonication and optimized using Box-Behnken design. Optimized NE showed Z-average of 211.2 nm, polydispersity index of 0.343, and zeta potential of -32.7 mV. Optimized P60+ CUR NE was characterized by stability testing and transmission electron microscopy, and it was observed that NE was stable at 4°C for 30 days and monodisperse in nature with particle size of 195-205 nm. P60+ CUR NE was further formulated as gel and characterized by viscosity, growth curve analysis, and in vitro permeation studies. In vitro drug permeation studies in simulated vaginal media showed maximum permeation (84 ± 0.21%) of curcumin within 5 h and (91 ± 0.16%) of P60 within 8 h. Both the drugs maintained sustained permeation for 12 h. To investigate the transport via intravaginal route, gamma scintigraphy and biodistribution study of P60 + CUR NBG was performed on Sprague-Dawley rats using 99mtechnetium pertechnetate for radiolabeling to P60 molecule. Following intravaginal administration, P60 + CUR NBG dispersed in the kidney and urinary bladder with (3.07 ± 0.15) and (3.35 ± 0.45) percentage per gram after 3 h for P60 and CUR, respectively, and remained active for 12 h. Scintigraphy images suggested that the P60 + CUR NBG given by intravaginal route led to effective distribution of actives in urinary tract, and this observation was in agreement with the biodistribution results.

Antimicrobial Peptides as Anti-Infectives against Staphylococcus epidermidis.

Staphylococcus epidermidis has emerged as the main causative agent for graft-related and nosocomial infections. Rampant use of antibiotics and biofilm formed by the organism results in poor penetration of the drug and further aggravates the antibiotic resistance, emphasizing an urgent need to explore alternative treatment modalities. Antimicrobial peptides (AMPs), produced as effector molecules of the innate immunity of living organisms, have therapeutic potential that can be used to inhibit the growth of microbes. In addition, the susceptibility of a microbe to become resistant to an AMP is relatively low. The AMPs are amphipathic peptides of 12-100 residues, which have broad-spectrum activity against microbes. There are scattered reports of AMPs listed against S. epidermidis and there is an urgent need to systematically study the AMPs. Various natural AMPs as well as synthetic peptides have been investigated against S. epidermidis. These peptides have been shown to inhibit both planktonic culture and S. epidermidis biofilm effectively. The multiple modes of action in killing the organism minimize the chances for the development of resistance. This review focused on various natural and synthetic peptides that demonstrate activity against S. epidermidis.

Host-pathogen interactome analysis of Chikungunya virus envelope proteins E1 and E2.

The envelope proteins of Chikungunya virus (CHIKV) are known to play crucial roles in viral infection and spread. Although the role of envelope proteins in viral infection has been studied, the cellular interactors of these proteins are still elusive. In the present study, the ectodomains of CHIKV envelope proteins (E1 and E2) have been used for a high throughput yeast two-hybrid (Y2H) screening to identify the interacting host protein partners. Following a comparative analysis between the viral-host protein interaction data generated from Y2H and computational approach, five host proteins interacting with E1 and three host proteins interacting with E2 common to both datasets were identified. These associations were further verified independently by pull down and protein interaction ELISA. The identified interactions shed light on the possible cellular machinery that CHIKV might be employing during viral entry, trafficking, and evasion of immune system.

Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles.

The objective of the present investigation was to optimize diazepam (Dzp)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) to achieve delivery in the brain through intranasal administration. Dzp nanoparticles (DNP) were formulated by nanoprecipitation and optimized using Box-Behnken design. The influence of various independent process variables (polymer, surfactant, aqueous to organic (w/o) phase ratio, and drug) on resulting properties of DNP (z-average and drug entrapment) was investigated. Developed DNP showed z-average 148-337 d.nm, polydispersity index 0.04-0.45, drug entrapment 69-92%, and zeta potential in the range of -15 to -29.24 mV. Optimized DNP were further analyzed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), ex-vivo drug release, and in-vitro cytotoxicity. Ex-vivo drug release study via sheep nasal mucosa from DNP showed a controlled release of 64.4% for 24 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay performed on Vero cell line showed less toxicity for DNP as compared to Dzp suspension (DS). Gamma scintigraphy and biodistribution study of DNP and DS was performed on Sprague-Dawley rats using technetium-99m-labeled ((99m)Tc) Dzp formulations to investigate the nose-to-brain drug delivery pathway. Brain/blood uptake ratios, drug targeting efficiency, and direct nose-to-brain transport were found to be 1.23-1.45, 258, and 61% for (99m)Tc-DNP (i.n) compared to (99m)Tc-DS (i.n) (0.38-1.06, 125, and 1%). Scintigraphy images showed uptake of Dzp from nose-to-brain, and this observation was in agreement with the biodistribution results. These results suggest that the developed poly(D,L-lactide-co-glycolide) (PLGA) NP could serve as a potential carrier of Dzp for nose-to-brain delivery in outpatient management of status epilepticus.

Pseudomonas aeruginosa biofilm: potential therapeutic targets.

Pseudomonas aeruginosa is a gram-negative pathogen that has become an important cause of infection, especially in patients with compromised host defense mechanisms. It is frequently related to nosocomial infections such as pneumonia, urinary tract infections (UTIs) and bacteremia. The biofilm formed by the bacteria allows it to adhere to any surface, living or non-living and thus Pseudomonal infections can involve any part of the body. Further, the adaptive and genetic changes of the micro-organisms within the biofilm make them resistant to all known antimicrobial agents making the Pseudomonal infections complicated and life threatening. Pel, Psl and Alg operons present in P. aeruginosa are responsible for the biosynthesis of extracellular polysaccharide which plays an important role in cell-cell and cell-surface interactions during biofilm formation. Understanding the bacterial virulence which depends on a large number of cell-associated and extracellular factors is essential to know the potential drug targets for future studies. Current novel methods like small molecule based inhibitors, phytochemicals, bacteriophage therapy, photodynamic therapy, antimicrobial peptides, monoclonal antibodies and nanoparticles to curtail the biofilm formed by P. aeruginosa are being discussed in this review.

Combinatorial antimicrobial effect of curcumin with selected phytochemicals on Staphylococcus epidermidis.

Staphylococcus epidermidis is reported to be the main causative agent of nosocomial infections. It has become increasingly difficult to treat this micro-organism because of the emergence of new antibiotic-resistant strains and its ability to form biofilm on medical associated devices. Phytochemicals acting in synergy are effective in killing the micro-organisms by lowering the doses, and synergistic compounds evade the development of resistance due to different mechanism of action. This study aims to determine the synergistic antimicrobial potential of curcumin with cinnamaldehyde, eugenol, and ellagic acid against S. epidermidis. Curcumin with ellagic acid as well as eugenol were found to have additive antimicrobial effect, whereas, in combination, curcumin and cinnamaldehyde were found to have synergistic effect against S. epidermidis (fractional inhibitory concentration index (FICI) = 0.5). Synergy between curcumin and cinnamaldehyde was established by time-kill kinetics and was further evaluated for antibiofilm activity. The dose required to inhibit biofilm formation was reduced to half than that needed to inhibit its planktonic culture (minimal inhibitory concentration (MIC) of curcumin = 3.12 µg/ml; MIC of cinnamaldehyde = 15.62 µg/ml; FICI = 0.248). Both curcumin and cinnamaldehyde disrupted the bacterial membrane for killing the bacteria as determined by permeability studies on Escherichia coli ML-35p.

An Insight into Emerging Phytocompounds for Glioblastoma Multiforme Therapy.

Despite intense research in the field of glioblastoma multiforme (GBM) therapeutics, the resistance against approved therapy remains an issue of concern. The resistance against the therapy is widely reported due to factors like clonal selection, involvement of multiple developmental pathways, and majorly defective mismatch repair (MMR) mediated by O6- methylguanine DNA methyltransferase (MGMT). Phytotherapy is one of the most effective alternatives to overcome resistance. It involves plant-based compounds, divided into several classes: alkaloids; phenols; terpenes; organosulfur compounds. The phytocompounds comprised in these classes are extracted or processed from certain plant sources. They can target various proteins of molecular pathways associated with the progression and survival of GBM. Phytocompounds have also shown promise as immunomodulatory agents and are being explored for immune checkpoint inhibition. Therefore, research and innovations are required to understand the mechanism of action of such phytocompounds against GBM to develop efficacious treatments for the same. This review gives insight into the potential of phytochemical-based therapeutic options for GBM treatment.

Comparative analysis of α-pinene alone and combined with temozolomide in human glioblastoma cells.

α-Pinene (PEN) is a phyto compound present in terpene plants. In traditional medicine, PEN has been used for its anti-inflammatory, pain-relieving, and bronchodilator properties. The effect of PEN in combination with temozolomide (TMZ) in glioblastoma multiforme (GBM) cells has been evaluated. The action of the PEN + TMZ combination on cell migration, soft-agar, and cell death was determined in LN229 and U87MG human glioblastoma cells. In combination, PEN with TMZ showed a synergistic inhibitory effect in the GBM cells. The PEN + TMZ treatment showed a higher fluorescent intensity and reduced the percentage of wound area closure compared to the compound alone. The compounds in combination also resulted in a reduction in single-cell colony formation. To conclude, the study showed that plant-derived PEN enhanced the effectiveness of standard chemotherapeutic, TMZ, in LN229 and U87MG cells.

MicroRNA as a potential biomarker for systemic lupus erythematosus: pathogenesis and targeted therapy.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with hyperactive innate and adaptive immune systems that cause dermatological, cardiovascular, renal, and neuropsychiatric problems in patients. SLE's multifactorial nature and complex pathogenesis present significant challenges in its clinical classification. In addition, unpredictable treatment responses in patients emphasize the need for highly specific and sensitive SLE biomarkers that can assist in understanding the exact pathogenesis and, thereby, lead to the identification of novel therapeutic targets. Recent studies on microRNA (miRNA), a non-coding region involved in the regulation of gene expression, indicate its importance in the development of the immune system and thus in the pathogenesis of various autoimmune disorders such as SLE. miRNAs are fascinating biomarker prospects for SLE categorization and disease monitoring owing to their small size and high stability. In this paper, we have discussed the involvement of a wide range of miRNAs in the regulation of SLE inflammation and how their modulation can be a potential therapeutic approach.

Intraviral protein interactions of Chandipura virus.

Chandipura virus (CHPV) is an emerging rhabdovirus responsible for several outbreaks of fatal encephalitis among children in India. The characteristic structure of the virus is a result of extensive and specific interplay among its five encoded proteins. The revelation of interactions among CHPV proteins can help in gaining insight into viral architecture and pathogenesis. In the current study, we carried out comprehensive yeast two-hybrid (Y2H) analysis to elucidate intraviral protein-protein interactions. All of the interactions identified by Y2H were assessed for reliability by GST pull-down and ELISA. A total of eight interactions were identified among four viral proteins. Five of these interactions are being reported for the first time for CHPV. Among these, the glycoprotein (G)-nucleocapsid (N) interaction could be considered novel, as this has not been reported for any members of the family Rhabdoviridae. This study provides a framework within which the roles of the identified protein interactions can be explored further for understanding the biology of this virus at the molecular level.

Deciphering the human cellular interactors of alphavirus unique domain of chikungunya virus.

The life-threatening re-emerged chikungunya virus (CHIKV) can cause an epidemic outbreak and still has no vaccine available so far. Alphavirus unique domain (AUD) of CHIKV nsP3 is a multifunctional domain that remains conserved among alphaviruses and is critical for CHIKV replication. The understanding of AUD-host protein-protein interactions and their association with the cellular processes concerning CHIKV infection are not well studied. In the current study, the protein-protein interactions of AUD and its human host were elucidated by screening of universal human cDNA library using yeast two-hybrid system. The chosen interactions were further validated by GST pull-down assay, and their network mapping was analyzed. The study revealed that the identified interactors are linked with the vesicle trafficking and transcription corepressor activities. Further, the interfacial residues of interactions between viral and host proteins were predicted, which will further provide the new platform to develop novel antivirals.

Antiviral Peptides: Identification and Validation.

Despite rapid advances in the human healthcare, the infection caused by certain viruses results in high morbidity and mortality accentuate the importance for development of new antivirals. The existing antiviral drugs are limited, due to their inadequate response, increased rate of resistance and several adverse side effects. Therefore, one of the newly emerging field "peptide-based therapeutics" against viruses is being explored and seems promising. Over the last few years, a lot of scientific effort has been made for the identification of novel and potential peptide-based therapeutics using various advanced technologies. Consequently, there are more than 60 approved peptide drugs available for sale in the market of United States, Europe, Japan, and some Asian countries. Moreover, the number of peptide drugs undergoing the clinical trials is rising gradually year by year. The peptide-based antiviral therapeutics have been approved for the Human immunodeficiency virus (HIV), Influenza virus and Hepatitis virus (B and C). This review enlightens the various peptide sources and the different approaches that have contributed to the search of potential antiviral peptides. These include computational approaches, natural and biological sources (library based high throughput screening) for the identification of lead peptide molecules against their target. Further the applications of few advanced techniques based on combinatorial chemistry and molecular biology have been illustrated to measure the binding parameters such as affinity and kinetics of the screened interacting partners. The employment of these advanced techniques can contribute to investigate antiviral peptide therapeutics for emerging infections.

Computational analysis of human host binding partners of chikungunya and dengue viruses during coinfection.

Mosquito-borne viral diseases like chikungunya and dengue infections can cause severe illness and have become major public health concerns. Chikungunya virus (CHIKV) and dengue virus (DENV) infections share similar primary clinical manifestations and are transmitted by the same vector. Thus, the probability of their coinfection gets increased with more severe clinical complications in the patients. The present study was undertaken to elucidate the common human interacting partners of CHIKV and DENV proteins during coinfection. The viral-host protein-protein interactome was constructed using Cytoscape. Subsequently, significant host interactors were identified during coinfection. The network analysis elucidated 57 human proteins interacting with both CHIKV and DENV, represented as hub-bottlenecks. The functional and biological analyses of the 40 hub-bottlenecks revealed that they are associated with phosphoinositide 3-kinases (PI3K)/AKT, p53 signaling pathways, regulation of cell cycle and apoptosis during coinfection. Moreover, the molecular docking analysis uncovered the tight and robust binding of selected hub-bottlenecks with CHIKV/DENV proteins. Additionally, 23 hub-bottlenecks were predicted as druggable candidates that could be targeted to eradicate the host-viral interactions. The elucidated common host binding partners during DENV and CHIKV coinfection as well as indicated approved drugs can support the therapeutics development.

Computational approach to decipher cellular interactors and drug targets during co-infection of SARS-CoV-2, Dengue, and Chikungunya virus.

The world is reeling under severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and it will be frightening if compounded by other co-existing infections. The co-occurrence of the Dengue virus (DENV) and Chikungunya virus (CHIKV) has been into existence, but recently the co-infection of DENV and SARS-CoV-2 has been reported. Thus, the possibility of DENV, CHIKV, and SARS-CoV-2 co-infection could be predicted in the future with enhanced vulnerability. It is essential to elucidate the host interactors and the connected pathways to understand the biological insights. The in silico approach using Cytoscape was exploited to elucidate the common human proteins interacting with DENV, CHIKV, and SARS-CoV-2 during their probable co-infection. In total, 17 interacting host proteins were identified showing association with envelope, structural, non-structural, and accessory proteins. Investigating the functional and biological behaviour using PANTHER, UniProtKB, and KEGG databases uncovered their association with several cellular pathways including, signaling pathways, RNA processing and transport, cell cycle, ubiquitination, and protein trafficking. Withal, exploring the DrugBank and Therapeutic Target Database, total seven druggable host proteins were predicted. Among all integrin beta-1, histone deacetylase-2 (HDAC2) and microtubule affinity-regulating kinase-3 were targeted by FDA approved molecules/ drugs. Furthermore, HDAC2 was predicted to be the most significant target, and some approved drugs are available against it. The predicted druggable targets and approved drugs could be investigated to obliterate the identified interactions that could assist in inhibiting viral infection.

Identification of Peptide Binders to Truncated Recombinant Chikungunya Virus Envelope Protein 2 Using Phage Display Technology and Their In Silico Characterization.

AIM: To identify and characterize peptide binders to truncated recombinant chikungunya virus envelope protein 2. BACKGROUND: Despite extensive research on the chikungunya virus (CHIKV), the specific antiviral treatment's unavailability has stressed the need for the urgent development of therapeutics. The Envelope protein 2 (E2) of CHIKV that displays putative receptor binding sites and specific epitopes for virus neutralizing antibodies is a critical target for the therapeutic intervention. OBJECTIVE: The study aims to identify the unique peptides that can bind to truncated E2 protein of CHIKV and further explore their properties as potential therapeutic candidate. METHODS: A stretch of CHIKV-E2 (rE2), which is prominently exposed on the surface of virion, was used as bait protein to identify peptide binders to the CHIKV-rE2 using a 12-mer phage display peptide library. Three rounds of biopanning yielded several peptide binders to CHIKV-rE2 and their binding affinities were compared by phage ELISA. Additionally, a fully flexible-blind docking simulation investigated the possible binding modes of the selected peptides. Furthermore, the selected peptides were characterized and their ADMET properties were explored in silico. RESULTS: Five peptides were identified as potential binders based on their robust reactivity to the bait protein. The selected peptides appeared to interact with the crucial residues that were notably exposed on the surface of E1-E2 trimeric structure. The explored in silico studies suggested their non-allergenicity, non-toxicity and likeliness to be antiviral. CONCLUSION: The potential binding peptides of CHIKV-rE2 protein were identified using phage display technology and characterized in silico. The selected peptides could be further used for the development of therapeutics against the CHIKV infection.>.

Antiviral therapeutics for chikungunya virus.

Introduction: Chikungunya virus (CHIKV), a reemerging human arthropod borne virus, can causes global epidemic outbreaks and has become a serious health concern due to the unavailability of any antiviral therapy/vaccine. Extensive research has been conducted to target different proteins from CHIKV to curtail the spread of virus.Areas covered: This review provides an overview of the granted patents including the current status of antiviral strategies targeting CHIKV.Expert opinion: Under the current scenario, potential molecules and different approaches have been utilized to suppress CHIKV infection. MV-CHIKV and VRC-CHKVLP059-00-VP vaccine candidates have successfully completed phase I clinical trials and ribavirin (inhibitor) has shown significant inhibition of CHIKV replication and could be the most promising candidates. The drug resistance and toxicity can be modulated by using the inhibitors/drugs in combination. Moreover, nanoparticle formulations can improve the efficacy and bioavailability of drugs.