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Rational Drug Discovery of HCV Helicase Inhibitor: Improved Docking Accuracy with Multiple Seeding in AutoDock Vina and In Situ Minimization

Lim SK, Othman R, Yusof R, Heh CH

Curr Comput Aided Drug Des, 2017;13(2):160-169.
PMID: 27903217 DOI: 10.2174/1573409912666161130122622

BACKGROUND: Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximately 3% of the global populations. Despite the current several direct antiviral agents in the treatment of Hepatitis C, the standard treatment for HCV infection is accompanied by several drawbacks, such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants.
OBJECTIVES: To discover potential inhibitors for HCV helicase through an optimized in silico approach.
METHODS: In this study, a homology model (HCV Genotype 3 helicase) was used as the target and screened through a benzopyran-based virtual library. Multiple-seedings of AutoDock Vina and in situ minimization were to account for the non-deterministic nature of AutoDock Vina search algorithm and binding site flexibility, respectively. ADME/T and interaction analyses were also done on the top hits via FAFDRUG3 web server and Discovery Studio 4.5.
RESULTS: This study involved the development of an improved flow for virtual screening via implemention of multiple-seeding screening approach and in situ minimization. With the new docking protocol, the redocked standards have shown better RMSD value in reference to their native conformations. Ten benzopyran-like compounds with satisfactory physicochemical properties were discovered to be potential inhibitors of HCV helicase. ZINC38649350 was identified as the most potential inhibitor.
CONCLUSION: Ten potential HCV helicase inhibitors were discovered via a new docking optimization protocol with better docking accuracy. These findings could contribute to the discovery of novel HCV antivirals and serve as an alternative approach of in silico rational drug discovery.
Antiviral actions of flavanoid-derived compounds on dengue virus type-2

Muhamad M, Kee LY, Rahman NA, Yusof R

Int J Biol Sci, 2010 May 23;6(3):294-302.
PMID: 20567498

Dengue viruses, mosquito-borne members of the Flaviviridae family, are the causative agents of dengue fever and its associated complications, dengue haemorrhagic fever and dengue shock syndrome. To date, more than 2.5 billion people in over 100 countries are at risk of infection, and approximately 20 million infections were reported annually. There is currently no treatment or vaccine available for dengue infection. This study employed a whole-cell organism model or in vitro methods to study the inhibitory property of the flavanoid-derived compounds against DENV2 activity. Results showed that at concentration not exceeding the maximum non-toxic dose (MNTD), these compounds completely prevented DENV2 infection in HepG2 cells as indicated by the absence of cytophatic effects. The in vitro antiviral activity assessed in HepG2 cells employing virus inhibition assay showed high inhibitory activity in a dose dependent manner. At concentration below MNTD, compounds exhibited inhibitory activity against DENV2 with a range of potency strengths of 72% to 100%. The plaque forming unit per ml (pfu/ml) was reduced prominently with a maximum reduction of 98% when the infected HepG2 cells were treated with the highest non-toxic dose of compounds. The highly potent activity of the compounds against DENV2 infection strongly suggests their potential as a lead antiviral agent for dengue.
Fulltext Effectiveness of school-based child sexual abuse intervention among school children in the new millennium era: Systematic review and meta-analyses

Che Yusof R, Norhayati MN, Mohd Azman Y

Front Public Health, 2022;10:909254.
PMID: 35937243 DOI: 10.3389/fpubh.2022.909254

INTRODUCTION: School-based child sexual abuse intervention programs were developed to educate the school children to protect them from sexual abuse. The programs were evaluated to make sure the interventions were effective in reducing child sexual abuse cases (CSA). This review aimed to determine the effectiveness of the school-based child sexual abuse intervention programs in the new millennium era (2000-2021) in improving the knowledge, skills, and attitude of school children under 18 years old toward child sexual abuse.
METHODS: A systematic search was conducted through MEDLINE (PubMed), EBSCO, and SCOPUS databases to collect full English articles related to school-based CSA intervention programs published from 2000 to 2021.
RESULTS: A total of 29 studies from randomized control trial and quasi-experimental from several countries was analyzed. Comparisons within group of pre-post intervention for knowledge, skills, and attitude were measured by standardized mean difference (SMD) and 95% CI of -1.06 (95% CI: -1.29, -0.84), -0.91 (95% CI: -1.2, -0.61), and -0.51 (95% CI: -3.61, 0.58), respectively. Meanwhile for between intervention and control group comparisons, the SMD of knowledge was 0.9 (95% CI: 0.63, 1.18), skills was 0.39 (95% CI: 0.07, 0.71), and attitude was 1.76 (95% CI: 0.46, 3.07).
CONCLUSION: The programs were found to be effective in improving the knowledge, skills, and attitude of the students from pre-intervention to post-intervention and between the intervention and control groups.Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022312383, identifier: CRD42022312383.
Evaluation of neutralizing antibodies produced by papaya mosaic virus nanoparticles fused to the E2EP3 peptide epitope of Chikungunya envelope

Nor Rashid N, Teoh TC, Al-Harbi SJ, Yusof R, Rothan HA

Trop Biomed, 2021 Mar 01;38(1):36-41.
PMID: 33797522 DOI: 10.47665/tb.38.1.007

Chikungunya virus (CHIKV) infection is the cause of acute symptoms and chronic symmetrical polyarthritis associated with long-term morbidity and mortality. Currently, there is no available licensed vaccine or particularly useful drug for human use against CHIKV infection. This study was conducted to evaluate the efficacy of antibodies produced by papaya mosaic virus (PapMV) nanoparticles fused to E2EP3 peptide of CHIKV envelope as a recombinant CHIKV vaccine. PapMV, PapMV-C- E2EP3, and E2EP3-N-PapMV were produced in E. coli with an approximate size of 27 to 30 kDa. ICR mice (5 to 6 weeks of age) were injected subcutaneously with 25 micrograms of vaccine construct, and ELISA measured the titer of CHIKV specific IgG antibodies. The results showed that both recombinant proteins E2EP3-N-PapMV and PapMVC-E2EP3 were able to induce IgG antibodies production in immunized mice against CHIKV while immunization with recombinant PapMV showed no IgG antibodies induction. The neutralizing activity of the antibodies generated by either E2EP3-N-PapMV or PapMV-C-E2EP3 exhibited similar inhibition to CHIKV replication in Vero cells using the cells based antibody neutralizing assay and analyzed by plaque formation assay. This study showed the effectiveness of nanoparticles vaccine generated by fusing epitope peptide of CHIKV envelope to papaya mosaic virus envelope in inducing a robust immune response in mice against CHIKV. The data showed that levels of neutralizing antibodies correlate with a protective immune response CHIKV replication.
Fulltext Tetrabutylammonium bromide (TBABr)-based deep eutectic solvents (DESs) and their physical properties

Yusof R, Abdulmalek E, Sirat K, Rahman MB

Molecules, 2014 Jun 13;19(6):8011-26.
PMID: 24932572 DOI: 10.3390/molecules19068011

Density, viscosity and ionic conductivity data sets of deep eutectic solvents (DESs) formed by tetrabutylammonium bromide (TBABr) paired with ethlyene glycol, 1,3-propanediol, 1,5-pentanediol and glycerol hydrogen bond donors (HBDs) are reported. The properties of DES were measured at temperatures between 303 K and 333 K for HBD percentages of 66.7% to 90%. The effects of HBDs under different temperature and percentages are systematically analyzed. As expected, the measured density and viscosity of the studied DESs decreased with an increase in temperature, while ionic conductivity increases with temperature. In general, DESs made of TBABr and glycerol showed the highest density and viscosity and the lowest ionic conductivity when compared to other DESs. The presence of an extra hydroxyl group on glycerol in a DES affected the properties of the DES.
Fulltext Arteriovenous Malformation Hemorrhage in Pregnancy: A Systematic Review and Meta-Analysis

Che Yusof R, Norhayati MN, Mohd Azman Y

Int J Environ Res Public Health, 2022 Oct 13;19(20).
PMID: 36293763 DOI: 10.3390/ijerph192013183

Hemorrhage of arteriovenous malformation (AVM) is a rare condition during pregnancy. This study was proposed to pool the proportion of AVM hemorrhage per pregnancy. A systematic review and meta-analysis with three databases were performed to review the studies published until April 2022. The Newcastle Ottawa Scale was used for risk assessment of data quality. The meta-analysis was conducted by a generic inverse variance of double arcsine transformation with a random model using Stata software. Twelve studies were included in this review. The pooled proportion of AVM hemorrhage per pregnancy was 0.16 (95% CI: 0.08, 0.26). The subgroup analyses were carried out based on world regions and study designs, and the study duration with the highest proportion of each subgroup was Europe [0.35 (95% CI: 0.02, 0.79)], with retrospective review [0.18 (95% CI: 007, 0.32)] and 10 to 20 years of study duration [0.37 (95% CI: 0.06, 0.77)]. The AVM hemorrhage per pregnancy in this review was considered low. However, the conclusion must be carefully interpreted since this review had a small study limitation.
Fulltext Finding Lead Compounds for Dengue Antivirals from a Collection of Old Drugs through In Silico Target Prediction and Subsequent In Vitro Validation

Abdullah ZL, Chee HY, Yusof R, Mohd Fauzi F

ACS Omega, 2023 Sep 12;8(36):32483-32497.
PMID: 37720780 DOI: 10.1021/acsomega.3c02607

Dengue virus (DENV) infection is one of the most widely spread flavivirus infections. Despite the fatality it could cause, no antiviral treatment is currently available to treat the disease. Hence, this study aimed to repurpose old drugs as novel DENV NS3 inhibitors. Ligand-based (L-B) and proteochemometric (PCM) prediction models were built using 62,354 bioactivity data to screen for potential NS3 inhibitors. Selected drugs were then subjected to the foci forming unit reduction assay (FFURA) and protease inhibition assay. Finally, molecular docking was performed to validate these results. The in silico studies revealed that both models performed well in the internal and external validations. However, the L-B model showed better accuracy in the external validation in terms of its sensitivity (0.671). In the in vitro validation, all drugs (zileuton, trimethadione, and linalool) were able to moderately inhibit the viral activities at the highest concentration tested. Zileuton showed comparable results with linalool when tested at 2 mM against the DENV NS3 protease, with a reduction of protease activity at 17.89 and 18.42%, respectively. Two new compounds were also proposed through the combination of the selected drugs, which are ziltri (zilueton + trimethadione) and zilool (zileuton + linalool). The molecular docking study confirms the in vitro observations where all drugs and proposed compounds were able to achieve binding affinity ≥ -4.1 kcal/mol, with ziltri showing the highest affinity at -7.7 kcal/mol, surpassing the control, panduratin A. The occupation of both S1 and S2 subpockets of NS2B-NS3 may be essential and a reason for the lower binding energy shown by the proposed compounds compared to the screened drugs. Based on the results, this study provided five potential new lead compounds (ziltri, zilool, zileuton, linalool, and trimethadione) for DENV that could be modified further.
Fulltext Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication

Rothan HA, Bahrani H, Mohamed Z, Abd Rahman N, Yusof R

PLoS One, 2014;9(4):e94561.
PMID: 24722532 DOI: 10.1371/journal.pone.0094561

Dengue virus (DENV) broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1) and plectasin (PLSN) were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN) as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro) with half-maximal inhibitory concentration (IC50) 0.5±0.1 μM. The real-time proliferation assay (RTCA) and the end-point proliferation assay (MTT assay) showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities.
Association of dietary patterns with sociodemographic and health-related factors among coronary artery disease (CAD) patients

Esmaili H, Mohd Yusof R, Abu Saad H, Ghaemian A, Darani Zad N

Ecol Food Nutr, 2015;54(1):4-19.
PMID: 25347717 DOI: 10.1080/03670244.2014.930031

This study aimed to identify the association of dietary patterns with sociodemographic and health-related characteristics among coronary artery disease patients. In this cross-sectional study, the participants were 250 patients coronary artery disease aged ≥ 40 years old. Data collection was done using questionnaires related to sociodemographics, health-related factors, and food-frequency intake information. Three dietary patterns (traditional, western, and healthy) were obtained using principal component analysis. The result showed that dietary patterns were associated with sociodemographic and health-related factors. According to the result, all the factors were taken very seriously when planning a promotional program for healthy lifestyle in prevention of CAD.
Biosensing enhancement of dengue virus using microballoon mixers on centrifugal microfluidic platforms

Aeinehvand MM, Ibrahim F, Harun SW, Djordjevic I, Hosseini S, Rothan HA, et al.

Biosens Bioelectron, 2015 May 15;67:424-30.
PMID: 25220800 DOI: 10.1016/j.bios.2014.08.076

Dengue is the current leading cause of death among children in several Latin American and Asian countries. Due to poverty in areas where the disease is prevalent and the high cost of conventional diagnostic systems, low cost devices are needed to reduce the burden caused by dengue infection. Centrifugal microfluidic platforms are an alternative solution to reduce costs and increase the availability of a rapid diagnostic system. The rate of chemical reactions in such devices often depends on the efficiency of the mixing techniques employed in their microfluidic networks. This paper introduces a micromixer that operates by the expansion and contraction of a microballoon to produce a consistent periodical 3D reciprocating flow. We established that microballoons reduced mixing time of 12 μl liquids from 170 min, for diffusional mixing, to less than 23 s. We have also tested the effect of the microballoon mixers on the detection of the dengue virus. The results indicate that employing a microballoon mixer enhances the detection sensitivity of the dengue virus by nearly one order of magnitude compared to the conventional ELISA method.
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.
Fulltext Three-dimensional culture environment increases the efficacy of platelet rich plasma releasate in prompting skin fibroblast differentiation and extracellular matrix formation

Rothan HA, Djordjevic I, Bahrani H, Paydar M, Ibrahim F, Abd Rahmanh N, et al.

Int J Med Sci, 2014;11(10):1029-38.
PMID: 25136258 DOI: 10.7150/ijms.8895

Platelet rich plasma clot- releasate (PRCR) shows significant influence on tissue regeneration in clinical trials. Although, the mechanism of PRCR effect on fibroblast differentiation has been studied on 2D culture system, a detailed investigation is needed to establish the role of PRCR in cell seeded in 3D scaffolds. Therefore, a study was conducted to evaluate the influence of PRCR in fibroblasts (DFB) differentiation and extracellular matrix formation on both 3D and 2D culture systems. Cell viability was measured using MTT assay and DFB differentiation was evaluated by determining the expression levels of nucleostamin and alpha smooth muscle actin (α-SMA), using indirect immunostaining and Western blotting. The expression levels of extracellular matrix genes (collagen-I, collagen-III, fibronectin and laminin) and focal adhesion formation gene (integrin beta-1) were measured using Real-time PCR. The PRCR at 10% showed significant effect on cells viability compared with 5% and 20% in both culture environments. The decrease in the expression levels of nucleostamin and the increase in α-SMA signify the DFB differentiation to myofibroblast-like cells that was prominently greater in 3D compared to 2D culture. In 3D culture systems, the total collage production, expression levels of the extracellular matrix gene and the focal adhesion gene were increased significantly compared to 2D culture. In conclusion, 3D culture environments enhances the proliferative and differentiation effects of PRCR on DFB, thereby potentially increases the efficacy of DFB for future tissue engineering clinical application.
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.
Current approaches in antiviral drug discovery against the Flaviviridae family

Baharuddin A, Hassan AA, Sheng GC, Nasir SB, Othman S, Yusof R, et al.

Curr Pharm Des, 2014;20(21):3428-44.
PMID: 24001228

Viruses belonging to the Flaviviridae family primarily spread through arthropod vectors, and are the major causes of illness and death around the globe. The Flaviviridae family consists of 3 genera which include the Flavivirus genus (type species, yellow fever virus) as the largest genus, the Hepacivirus (type species, hepatitis C virus) and the Pestivirus (type species, bovine virus diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted by mosquitoes and ticks that take over host cell machinery in order to propagate. However, hepaciviruses and pestiviruses are not antropod-borne. Despite the extensive research and public health concern associated with flavivirus diseases, to date, there is no specific treatment available for any flavivirus infections, though commercially available vaccines for yellow fever, Japanese encephalitis and tick-born encephalitis exist. Due to the global threat of viral pandemics, there is an urgent need for new drugs. In many countries, patients with severe cases of flavivirus infections are treated only by supportive care, which includes intravenous fluids, hospitalization, respiratory support, and prevention of secondary infections. This review discusses the strategies used towards the discovery of antiviral drugs, focusing on rational drug design against Dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), Yellow Fever virus (YFV) and Hepatitis C virus (HCV). Only modified peptidic, nonpeptidic, natural compounds and fragment-based inhibitors (typically of mass less than 300 Da) against structural and non-structural proteins are discussed.
Fulltext Differential proteome analysis of chikungunya virus infection on host cells

Thio CL, Yusof R, Abdul-Rahman PS, Karsani SA

PLoS One, 2013;8(4):e61444.
PMID: 23593481 DOI: 10.1371/journal.pone.0061444

Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus that has caused multiple unprecedented and re-emerging outbreaks in both tropical and temperate countries. Despite ongoing research efforts, the underlying factors involved in facilitating CHIKV replication during early infection remains ill-characterized. The present study serves to identify host proteins modulated in response to early CHIKV infection using a proteomics approach.
Fragment-based molecular design of new competitive dengue Den2 Ns2b/Ns3 inhibitors from the components of fingerroot (Boesenbergia rotunda)

Frimayanti N, Zain SM, Lee VS, Wahab HA, Yusof R, Abd Rahman N

In Silico Biol. (Gedrukt), 2011;11(1-2):29-37.
PMID: 22475750 DOI: 10.3233/ISB-2012-0442

Publication year=2011-2012
The use of two-dimension electrophoresis to identify serum biomarkers from patients with dengue haemorrhagic fever

Thayan R, Huat TL, See LL, Tan CP, Khairullah NS, Yusof R, et al.

Trans R Soc Trop Med Hyg, 2009 Apr;103(4):413-9.
PMID: 19203772 DOI: 10.1016/j.trstmh.2008.12.018

Dengue infection is a major public health problem affecting millions of people living in tropical countries. With no suitable vaccines and specific antiviral drugs, treatment for dengue is usually symptomatic and supportive. Early diagnosis and recognition of severe disease is therefore crucial for better management of the patient. Two-dimension electrophoresis was used to identify disease-associated proteins that can be used for diagnosis and as drug targets for treatment. Two markers, identified by mass spectrometry analysis as alpha1-antitrypsin and NS1 proteins were found to be upregulated in dengue fever (DF; n=10) and dengue haemorrhagic fever (DHF; n=10) patients compared with healthy individuals (n=8). Both alpha1-antitrypsin and NS1 proteins were overexpressed two-fold in DHF patients compared with DF patients. Our study suggests that alpha1-antitrypsin and NS1 protein could be used as biomarkers as early indicators of DHF risk among patients with suspected dengue infection.
Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites

Othman R, Kiat TS, Khalid N, Yusof R, Newhouse EI, Newhouse JS, et al.

J Chem Inf Model, 2008 Aug;48(8):1582-91.
PMID: 18656912 DOI: 10.1021/ci700388k

A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.
Patients with nasopharyngeal carcinoma demonstrate enhanced serum and tissue ceruloplasmin expression

Doustjalali SR, Yusof R, Govindasamy GK, Bustam AZ, Pillay B, Hashim OH

J. Med. Invest., 2006 Feb;53(1-2):20-8.
PMID: 16537992

The proteomics approach was adopted to study the simultaneous expression of serum proteins in patients with nasopharyngeal carcinoma (NPC). We have subjected unfractionated whole sera of ten newly diagnosed Malaysian Chinese patients with WHO type III NPC to two-dimensional gel electrophoresis (2-DE) and image analysis. The results obtained were then compared to that generated from sera of ten normal healthy controls of the same ethnic group and range of age. Our data demonstrated that the serum high abundance 2-DE protein profiles of NPC patients were generally similar to that of the controls, with exception of the ceruloplasmin (CPL) spots (identified by mass spectrometric analysis and MASCOT database search), which showed higher expression. The enhanced expression of CPL in the patients' sera was confirmed by competitive ELISA. Immunohistochemical analysis of nasopharyngeal lesions of NPC patients demonstrated moderate to strong positive CPL staining in the cytoplasm of cells at the regions of malignancy but only weak cytoplasmic staining at normal epithelial lining areas. When follow-up 2-DE and ELISA studies were performed on five of the NPC patients who responded positively to six months treatment, the difference in CPL expression was no longer significant.
Fulltext Inhibition of dengue NS2B-NS3 protease and viral replication in Vero cells by recombinant retrocyclin-1

Rothan HA, Han HC, Ramasamy TS, Othman S, Rahman NA, Yusof R

BMC Infect Dis, 2012;12:314.
PMID: 23171075 DOI: 10.1186/1471-2334-12-314

Global resurgence of dengue virus infections in many of the tropical and subtropical countries is a major concern. Therefore, there is an urgent need for the development of successful drugs that are both economical and offer a long-lasting protection. The viral NS2B-NS3 serine protease (NS2B-NS3pro) is a promising target for the development of drug-like inhibitors, which are not available at the moment. In this study, we report retrocyclin-1 (RC-1) production in E. coli as a recombinant peptide to test against dengue NS2B-NS3pro.

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