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Fulltext Investigation of twenty selected medicinal plants from Malaysia for anti-Chikungunya virus activity

Chan YS, Khoo KS, Sit NWW

Int Microbiol, 2016 Sep;19(3):175-182.
PMID: 28494087 DOI: 10.2436/20.1501.01.275

Chikungunya virus is a reemerging arbovirus transmitted mainly by Aedes mosquitoes. As there are no specific treatments available, Chikungunya virus infection is a significant public health problem. This study investigated 120 extracts from selected medicinal plants for anti-Chikungunya virus activity. The plant materials were subjected to sequential solvent extraction to obtain six different extracts for each plant. The cytotoxicity and antiviral activity of each extract were examined using African monkey kidney epithelial (Vero) cells. The ethanol, methanol and chloroform extracts of Tradescantia spathacea (Commelinaceae) leaves showed the strongest cytopathic effect inhibition on Vero cells, resulting in cell viabilities of 92.6% ± 1.0% (512 μg/ml), 91.5% ± 1.7% (512 μg/ml) and 88.8% ± 2.4% (80 μg/ml) respectively. However, quantitative RT-PCR analysis revealed that the chloroform extract of Rhapis excelsa (Arecaceae) leaves resulted in the highest percentage of reduction of viral load (98.1%), followed by the ethyl acetate extract of Vernonia amygdalina (Compositae) leaves (95.5%). The corresponding 50% effective concentrations (EC50) and selectivity indices for these two extracts were 29.9 ± 0.9 and 32.4 ± 1.3 μg/ml, and 5.4 and 5.1 respectively. Rhapis excelsa and Vernonia amygdalina could be sources of anti-Chikungunya virus agents. [Int Microbiol 19(3):175-182 (2016)].

Matched MeSH terms: Antiviral Agents/isolation & purification
Fulltext Evaluation of luciferase and GFP-expressing Nipah viruses for rapid quantitative antiviral screening

Lo MK, Nichol ST, Spiropoulou CF

Antiviral Res, 2014 Jun;106:53-60.
PMID: 24680955 DOI: 10.1016/j.antiviral.2014.03.011

Nipah virus (NiV) outbreaks have occurred in Malaysia, India, and Bangladesh, and the virus continues to cause annual outbreaks of fatal human encephalitis in Bangladesh due to spillover from its bat host reservoir. Due to its high pathogenicity, its potential use for bio/agro-terrorism, and to the current lack of approved therapeutics, NiV is designated as an overlap select agent requiring biosafety level-4 containment. Although the development of therapeutic monoclonal antibodies and soluble protein subunit vaccines have shown great promise, the paucity of effective antiviral drugs against NiV merits further exploration of compound libraries using rapid quantitative antiviral assays. As a proof-of-concept study, we evaluated the use of fluorescent and luminescent reporter NiVs for antiviral screening. We constructed and rescued NiVs expressing either Renilla luciferase or green fluorescent protein, and characterized their reporter signal kinetics in different cell types as well as in the presence of several inhibitors. The 50% effective concentrations (EC50s) derived for inhibitors against both reporter viruses are within range of EC50s derived from virus yield-based dose-response assays against wild-type NiV (within 1Log10), thus demonstrating that both reporter NiVs can serve as robust antiviral screening tools. Utilizing these live NiV-based reporter assays requires modest instrumentation, and circumvents the time and labor-intensive steps associated with cytopathic effect or viral antigen-based assays. These reporter NiVs will not only facilitate antiviral screening, but also the study of host cell components that influence the virus life cycle.

Matched MeSH terms: Antiviral Agents/isolation & purification*
Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication

Chen CJ, Michaelis M, Hsu HK, Tsai CC, Yang KD, Wu YC, et al.

J Ethnopharmacol, 2008 Oct 30;120(1):108-11.
PMID: 18762235 DOI: 10.1016/j.jep.2008.07.048

Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by the SARS coronavirus (SARS-CoV). The development of new antiviral agents for SARS-CoV is an important issue. We tried to find potential resource from Traditional Chinese medicine (TCM) for development of new drugs against SARS-CoV.

Matched MeSH terms: Antiviral Agents/isolation & purification
Hepatitis B virus peptide inhibitors: solution structures and interactions with the viral capsid

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

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

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

Matched MeSH terms: Antiviral Agents/isolation & purification
REPORT- Some ethanobotanically important plants from Cholistan area for anti avian influenza virus (AIV) H9N2 screening

Shahzad MI, Ashraf H, Aslam A, Parveen S, Kamran Z, Naz N, et al.

Pak J Pharm Sci, 2019 Nov;32(6):2751-2756.
PMID: 31969311

Avian influenza or bird flu is a common problem of domestic and wild birds. Some of its strains are able to cross the species barrier and cause infection in various members of class Mammalia. In view of relatively lesser efficacy of vaccines, antiviral therapies remain the only choice for the sustenance of mammals acquiring this highly devastating infection. This study is based on the evaluation of antiviral potential of methanol extracts of eleven selected Cholistani plants. The methanol extracts were prepared by using dried plants material followed by concentrating in a rotary evaporator and finally air dried before dissolving in nanopure water. The suspension was filter sterilized and subjected to in ovo antiviral assays. The allantoic fluids were harvested and haemagglutinin (HA) titers were determined. Among the eleven plants evaluated all methanol extracts were found effective against AIV H9N2 except S. baryosma extract. The medicinal plants O. compressa, N. procumbens, and S. surattense were found to be more effective than others and they retained HA titers at 0 after challenge. The next in order were extracts of O. esculentum, H. salicornicum and S. fruticosa which kept HA titers at 4, 8 and 16 respectively. The extracts of H. recurvum, P. antidotale, S. icolados and A. aspera were found less effective than above mentioned plant extracts and they kept the HA titers at 32, 64, 128 and 256 respectively. These results led us to conclude that the medicinal plants of Cholistan region are a rich source of antiviral agent(s) against AIV H9N2 and could be a source of cost effective alternate therapeutics.

Matched MeSH terms: Antiviral Agents/isolation & purification
Fulltext Virucidal activity of Garcinia parvifolia leaf extracts in animal cell culture

Adnan A, Allaudin ZN, Hani H, Loh HS, Khoo TJ, Ting KN, et al.

BMC Complement Altern Med, 2019 Jul 10;19(1):169.
PMID: 31291936 DOI: 10.1186/s12906-019-2586-5

BACKGROUND: Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities. In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity. Garcinia parvifolia is used in traditional medicine. Currently, the antiviral activity of G. parvifolia is not known.
METHODS: This study was conducted to determine the effects of ethyl acetate (45 L Ea), ethanol (45 L Et), and hexane (45 L H) leaf extracts of G. parvifolia on the infectivity of pseudorabies virus (PrV) in Vero cells. The antiviral effects of the extracts were determined by cytopathic effect (CPE), inhibition, attachment, and virucidal assays.
RESULTS: The 50% cytotoxicity concentration (CC50) values obtained were 237.5, 555.0, and

Matched MeSH terms: Antiviral Agents/isolation & purification
Fulltext Potential Antiviral Agents from Marine Fungi: An Overview

Moghadamtousi SZ, Nikzad S, Kadir HA, Abubakar S, Zandi K

Mar Drugs, 2015 Jul;13(7):4520-38.
PMID: 26204947 DOI: 10.3390/md13074520

Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity.

Matched MeSH terms: Antiviral Agents/isolation & purification*
Interests and policies of the state of Sarawak, Malaysia regarding intellectual property rights for plant derived drugs

Chung FJ

J Ethnopharmacol, 1996 Apr;51(1-3):201-4.
PMID: 9213617

Sarawak, on the island of Borneo, is known internationally for its rich rain forests, flora and fauna. Its rain forests, occupying two-thirds of its geographical area shelters 2500 tree species, 5500 flowering plants and over 20 000 different kinds of animals and insects. Such abundance of plants, and in particular, in the variety thereof, have attracted the attention of scientists involved in the field of research into their potential medicinal value. Recent discovery that two species of Calophyllum tree in the rain forests of Sarawak produce active anti-HIV agents, has, no doubt, intensified interest in the State's plant resources for scientific research.

Matched MeSH terms: Antiviral Agents/isolation & purification
Fulltext Screening of antiviral activities in medicinal plants extracts against dengue virus using dengue NS2B-NS3 protease assay

Rothan HA, Zulqarnain M, Ammar YA, Tan EC, Rahman NA, Yusof R

Trop Biomed, 2014 Jun;31(2):286-96.
PMID: 25134897 MyJurnal

Dengue virus infects millions of people worldwide and there is no vaccine or anti-dengue therapeutic available. Screening large numbers of medicinal plants for anti-dengue activities is an alternative strategy in order to find the potent therapeutic compounds. Therefore, this study was designed to identify anti-dengue activities in nineteen medicinal plant extracts that are used in traditional medicine. Local medicinal plants Vernonia cinerea, Hemigraphis reptans, Hedyotis auricularia, Laurentia longiflora, Tridax procumbers and Senna angustifolia were used in this study. The highest inhibitory activates against dengue NS2B-NS3pro was observed in ethanolic extract of S. angustifolia leaves, methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems. These findings were further verified by in vitro viral inhibition assay. Methanolic extract of V. cinerea leaves, ethanol extract of T. procumbens stems and at less extent ethanolic extract of S. angustifolia leaves were able to maintain the normal morphology of DENV2-infected Vero cells without causing much cytopathic effects (CPE). The percentage of viral inhibition of V. cinerea and T. procumbens extracts were significantly higher than S. angustifolia extract as measured by plaque formation assay and RT-qPCR. In conclusion, The outcome of this study showed that the methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems possessed high inhibitory activates against dengue virus that worth more investigation.

Matched MeSH terms: Antiviral Agents/isolation & purification
Fulltext Effect of Carica papaya Leaf Extract Capsule on Platelet Count in Patients of Dengue Fever with Thrombocytopenia

Gadhwal AK, Ankit BS, Chahar C, Tantia P, Sirohi P, Agrawal RP

J Assoc Physicians India, 2016 06;64(6):22-26.
PMID: 27739263

OBJECTIVE: Thrombocytopenia in dengue fever is a common and serious complication. However, no specific treatment is available for dengue fever induced thrombocytopenia. In few countries (Pakistan, Malaysia, Sri Lanka and other Asian countries) the leaf extract of Carica papaya has been effectively used for thrombocytopenia. So, the study is planned to access effect of Carica papaya leaf extract on platelet count in dengue fever patients.

METHODS: All participants were randomised into two groups, study group and control group; the study group was given papaya leaf extract capsule of 500 mg once daily and routine supportive treatment for consecutive five days. The controls were given only routine supportive treatment. Daily complete blood counts, platelet counts and haematocrit level, liver function test, renal function test of both groups were observed.

RESULTS: On the first day platelet count of study group and control group was (59.82±18.63, 61.06±20.03 thousands, p value 0.36). On the 2nd day platelet count of both study and control groups was not significantly different (61.67±19.46 and 59.93±19.52 thousands, p value 0.20) but on 3rd day platelet count of study group was significantly higher than control group (82.96±16.72, 66.45±17.36 thousands, p value < 0.01). On 4th and 5th day platelet count of study group (122.43±19.36 and 112.47±17.49 thousands respectively) was also significantly higher than the control group (88.75±21.65 and 102.59±19.35 thousands) (p value < 0.01). On 7th day platelet count of study group and control group were not significantly different (124.47±12.35 and 122.46±19.76 thousands respectively, p value 0.08). Average hospitalization period of study group v/s control group was 3.65±0.97 v/s 5.42±0.98 days (p value < 0.01). Average platelet transfusion requirement in study group was significantly less than control group (0.685 units per patient v/s 1.19 units per patient) (p value <0.01).

CONCLUSIONS: It is concluded that Carica papaya leaf extract increases the platelet count in dengue fever without any side effect and prevents the complication of thrombocytopenia. So, it can be used in dengue fever with thrombocytopenia patients.

Matched MeSH terms: Antiviral Agents/isolation & purification
5'-Methoxyarmillane, a Bioactive Sesquiterpenoid Aryl Ester from the Fungus Armillaria ostoyae

Orban AM, Eichberg J, Marner M, Breuer S, Patras MA, Mettal U, et al.

Chembiochem, 2024 Nov 04;25(21):e202400168.
PMID: 38738599 DOI: 10.1002/cbic.202400168

Higher fungi of the genus Armillaria belonging to the phylum Basidiomycota produce bioactive sesquiterpenoid aryl esters called melleolides. A bioactivity-guided discovery process led to the identification of the new melleolide 5'-methoxyarmillane (1) in organic extracts from the mycelium of Armillaria ostoyae. Remarkably, supplementation of rapeseed oil to the culture medium potato dextrose broth increased the production of 1 by a factor of six during the course of the 35 days fermentation. Compound 1 was isolated and its structure elucidated by UHPLC-QTOF-HR-MS/MS and NMR spectroscopy. It showed toxicity against Madin-Darby canine kidney II (MDCK II, IC50 19.2 μg/mL, 44.1 μM) and human lung cancer Calu-3 cells (IC50 15.2 μg/mL, 34.9 μM) as well as moderate bioactivity against Mycobacterium tuberculosis (MIC 8 mg/mL, 18.4 μM) and Mycobacterium smegmatis (MIC 16 mg/mL, 36.8 μM), but not against Staphylococcus aureus, Escherichia coli, Candida albicans, and Septoria tritici. No inhibitory effects of 1 against the influenza viruses H3N2, H1N1pdm, B/Malaysia, and B/Massachusetts were observed.

Matched MeSH terms: Antiviral Agents/isolation & purification
Fulltext Inhibitory activities of microalgal extracts against Epstein-Barr virus DNA release from lymphoblastoid cells

Kok YY, Chu WL, Phang SM, Mohamed SM, Naidu R, Lai PJ, et al.

J Zhejiang Univ Sci B, 2011 May;12(5):335-45.
PMID: 21528487 DOI: 10.1631/jzus.B1000336

This study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus, Synechococcus elongatus, and Spirulina platensis against Epstein-Barr virus (EBV) in three Burkitt's lymphoma (BL) cell lines, namely Akata, B95-8, and P3HR-1. The antiviral activity was assessed by quantifying the cell-free EBV DNA using real-time polymerase chain reaction (PCR) technique. The methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in reducing cell-free EBV DNA (EC(50)<0.01 µg/ml) with a high therapeutic index (>28000). After fractionation by column chromatography, the fraction from Synechococcus elongatus (SEF1) reduced the cell-free EBV DNA most effectively (EC(50)=2.9 µg/ml, therapeutic index>69). Upon further fractionation by high performance liquid chromatography (HPLC), the sub-fraction SEF1'a was most active in reducing the cell-free EBV DNA (EC(50)=1.38 µg/ml, therapeutic index>14.5). This study suggests that microalgae could be a potential source of antiviral compounds that can be used against EBV.

Matched MeSH terms: Antiviral Agents/isolation & purification*
Fulltext Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide

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

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

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

Matched MeSH terms: Antiviral Agents/isolation & purification

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