Rational drug discovery: Ellagic acid as a potent dual-target inhibitor against hepatitis C virus genotype 3 (HCV G3) NS3 enzymes.

Structure-based virtual screening (SBVS) has served as a popular strategy for rational drug discovery. In this study, we aimed to discover novel benzopyran-based inhibitors that targeted the NS3 enzymes (NS3/4A protease and NS3 helicase) of HCV G3 using a combination of in silico and in vitro approaches. With the aid of SBVS, six novel compounds were discovered to inhibit HCV G3 NS3/4A protease and two phytochemicals (ellagic acid and myricetin) were identified as dual-target inhibitors that inhibited both NS3/4A protease and NS3 helicase in vitro (IC50  = 40.37 ± 5.47 nm and 6.58 ± 0.99 µm, respectively). Inhibitory activities against the replication of HCV G3 replicons were further assessed in a cell-based system with four compounds showed dose-dependent inhibition. Compound P8 was determined to be the most potent compound from the cell-based assay with an EC50 of 19.05 µm. The dual-target inhibitor, ellagic acid, was determined as the second most potent (EC50  = 32.37 µm) and the most selective in its inhibitory activity against the replication of HCV replicons, without severely affecting the viability of the host cells (selectivity index > 6.18).

A Microfluidic Lab-on-a-Disc (LOD) for Antioxidant Activities of Plant Extracts.

Antioxidants are an important substance that can fight the deterioration of free radicals and can easily oxidize when exposed to light. There are many methods to measure the antioxidant activity in a biological sample, for example 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant activity test, which is one of the simplest methods used. Despite its simplicity, the organic solvent that has been used to dilute DPPH is easily evaporated and degraded with respect to light exposure and time. Thus, it needs to be used at the earliest convenient time prior to the experiment. To overcome this issue, a rapid and close system for antioxidant activity is required. In this paper, we introduced the Lab-on-a-Disc (LoD) method that integrates the DPPH antioxidant activity test on a microfluidic compact disc (CD). We used ascorbic acid, quercetin, Areca catechu, Polygonum minus, and Syzygium polyanthum plant extracts to compare the results of our proposed LoD method with the conventional method. Contrasted to the arduous laborious conventional method, our proposed method offer rapid analysis and simple determination of antioxidant. This proposed LoD method for antioxidant activity in plants would be a platform for the further development of antioxidant assay.

The Importance of Some Plant Extracts as Skin Anti-aging Resources: A Review.

BACKGROUND: Skin is the largest and most visible organ of the body. Many of its functions include temperature regulation, immunity from microorganisms, maintaining electrolyte balance, and protection from physical injuries, chemical agents and ultraviolet (UV) radiation. Aging occurs in every layer of the skin, primarily due to the degradation of its components. Induction of degradative enzymes and the abundant production of reactive oxygen species lead to skin aging. Understanding the complexity of skin structure and factors contributing to the skin aging will help us impede the aging process. Applications of anti-aging products are a common method to prevent or repair damages that lead to aging. CONCLUSION: This review will provide information on the causes and indicators of skin aging as well as examine studies that have used plants to produce anti-aging products.

A combination of doxycycline and ribavirin alleviated chikungunya infection.

Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY and RIBA was determined to be 10.95±2.12 µM and 15.51±1.62 µM respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 µM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease.

Inhibitory effects of a peptide-fusion protein (Latarcin-PAP1-Thanatin) against chikungunya virus.

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.

Boesenbergia rotunda: From Ethnomedicine to Drug Discovery.

Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.

Inhibitory potential of Quercus lusitanica extract on dengue virus type 2 replication.

This study reports the in vitro inhibitory potential of crude extract of Quercus lusitanica (Q. lusitanica) seeds on the replication of dengue virus type 2 (DEN-2). In vitro antiviral activity of Q. lusitanica extract, assessed in C6/36 cells (cloned cells of Aedes albopictus larvae) employing a virus inhibition assay, showed dose-dependent inhibition. The Q. lusitanica extract at its maximum non-toxic concentration of 0.25 mg/ml completely inhibited 10-1,000 TCID50 of virus, as indicated by the absence of cytopathic effect (CPE). The low dose of Q. lusitanica (0.032 mg/ml) showed 100% inhibition with 10 TCID50 of virus, but only 50% and 25% inhibition with 100 and 1,000 TCID50, respectively. The NS1 is a glycoprotein present in all flaviviruses and appears essential for virus viability. To further evaluate Q. lusitanica extract as an antiviral compound, we investigated the effect of Q. lusitanica extract on the NS1 protein expression of infected C6/36 cells through proteomics technique. The result showed downregulation of NS1 protein expression of infected C6/36 cells after treatment with this extract. In conclusion, we found that Q. lusitanica extract has a good inhibitory effect on the replication of dengue virus type 2, both in conventional cell culture and proteomics technique.