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Article: Editorial:

Buroni, Silvia / Samy, Ramar Perumal

2023 Volume 14, Page(s) 1226865

Language	English
Publishing date	2023-06-06
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1226865
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Article ; Online: Design of novel pyrimidine based remdesivir analogues with dual target specificity for SARS CoV-2: A computational approach.

Dinesh, T V / Malgija, Beutline / Ponraj, Mano Ranjana / Muralakar, Pavankumar / Thathapudi, Jesse Joel / Kandasamy, Ruckmani / Alagarmalai, Jeyasankar / Balakrishnan, Anna Benedict / Ramar, Perumal Samy / James, Jannet Vennila / Bhagavathsingh, Jebasingh

International journal of biological macromolecules

2023 Volume 242, Issue Pt 1, Page(s) 124443

Abstract: As the world undergone unpreceded time of tragedy with the corona virus, many researchers have raised to showcase their scientific contributions in terms of novel configured anti-viral drugs until now. Herein, we designed pyrimidine based nucleotides and ...

Abstract	As the world undergone unpreceded time of tragedy with the corona virus, many researchers have raised to showcase their scientific contributions in terms of novel configured anti-viral drugs until now. Herein, we designed pyrimidine based nucleotides and assessed for the binding capability with SARS-CoV-2 viral replication targets of nsp12 RNA-dependent RNA polymerase and M
MeSH term(s)	Humans ; SARS-CoV-2/metabolism ; Molecular Docking Simulation ; COVID-19 ; COVID-19 Drug Treatment ; Antiviral Agents/chemistry ; RNA-Dependent RNA Polymerase/genetics ; Molecular Dynamics Simulation ; Pyrimidines/pharmacology
Chemical Substances	remdesivir (3QKI37EEHE) ; Antiviral Agents ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; Pyrimidines
Language	English
Publishing date	2023-05-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.124443
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Article ; Online: Diagnosis and biomarkers for ocular tuberculosis: From the present into the future.

Ludi, Zhang / Sule, Ashita Ashish / Samy, Ramar Perumal / Putera, Ikhwanuliman / Schrijver, Benjamin / Hutchinson, Paul Edward / Gunaratne, Jayantha / Verma, Indu / Singhal, Amit / Nora, Rina La Distia / van Hagen, P Martin / Dik, Willem A / Gupta, Vishali / Agrawal, Rupesh

Theranostics

2023 Volume 13, Issue 7, Page(s) 2088–2113

Abstract: Tuberculosis is an airborne disease caused ... ...

Abstract	Tuberculosis is an airborne disease caused by
MeSH term(s)	Humans ; Tuberculosis, Ocular/diagnosis ; Proteomics ; Tuberculosis/microbiology ; Sensitivity and Specificity ; Multiplex Polymerase Chain Reaction ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-04-01
Publishing country	Australia
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.81488
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Article ; Online: Purification of PaTx-II from the Venom of the Australian King Brown Snake and Characterization of Its Antimicrobial and Wound Healing Activities.

Samy, Ramar Perumal / Mackessy, Stephen P / Jeyasankar, Alagarmalai / Ponraj, Mano Ranjana / Franco, Octavio Luiz / Cooper, Matthew A / Kandasamy, Matheswaran / Mohanta, Tapan Kumar / Bhagavathsingh, Jebasingh / Vaiyapuri, Sakthivel

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: Infections caused by multi-drug-resistant (MDR) bacteria are a global threat to human health. As venoms are the source of biochemically diverse bioactive proteins and peptides, we investigated the antimicrobial activity and murine skin infection model- ... ...

Abstract	Infections caused by multi-drug-resistant (MDR) bacteria are a global threat to human health. As venoms are the source of biochemically diverse bioactive proteins and peptides, we investigated the antimicrobial activity and murine skin infection model-based wound healing efficacy of a 13 kDa protein. The active component PaTx-II was isolated from the venom of
MeSH term(s)	Humans ; Animals ; Mice ; Colubridae ; Staphylococcus aureus ; Australia ; Wound Healing ; Anti-Infective Agents/pharmacology ; Cnidarian Venoms/pharmacology ; Collagen/pharmacology ; Peptides/pharmacology ; Cytokines/pharmacology ; Mammals
Chemical Substances	parasicyonis toxin ; Anti-Infective Agents ; Cnidarian Venoms ; Collagen (9007-34-5) ; Peptides ; Cytokines
Language	English
Publishing date	2023-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24054359
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Article ; Online: Purification of PaTx-II from the Venom of the Australian King Brown Snake and Characterization of Its Antimicrobial and Wound Healing Activities

Ramar Perumal Samy / Stephen P. Mackessy / Alagarmalai Jeyasankar / Mano Ranjana Ponraj / Octavio Luiz Franco / Matthew A. Cooper / Matheswaran Kandasamy / Tapan Kumar Mohanta / Jebasingh Bhagavathsingh / Sakthivel Vaiyapuri

International Journal of Molecular Sciences, Vol 24, Iss 4359, p

2023 Volume 4359

Abstract	Infections caused by multi-drug-resistant (MDR) bacteria are a global threat to human health. As venoms are the source of biochemically diverse bioactive proteins and peptides, we investigated the antimicrobial activity and murine skin infection model-based wound healing efficacy of a 13 kDa protein. The active component PaTx-II was isolated from the venom of Pseudechis australis (Australian King Brown or Mulga Snake). PaTx-II inhibited the growth of Gram-positive bacteria in vitro, with moderate potency (MICs of 25 µM) observed against S. aureus , E. aerogenes, and P. vulgaris . The antibiotic activity of PaTx-II was associated with the disruption of membrane integrity, pore formation, and lysis of bacterial cells, as evidenced by scanning and transmission microscopy. However, these effects were not observed with mammalian cells, and PaTx-II exhibited minimal cytotoxicity (CC 50 > 1000 µM) toward skin/lung cells. Antimicrobial efficacy was then determined using a murine model of S. aureus skin infection. Topical application of PaTx-II (0.5 mg/kg) cleared S. aureus with concomitant increased vascularization and re-epithelialization, promoting wound healing. As small proteins and peptides can possess immunomodulatory effects to enhance microbial clearance, cytokines and collagen from the wound tissue samples were analyzed by immunoblots and immunoassays. The amounts of type I collagen in PaTx-II-treated sites were elevated compared to the vehicle controls, suggesting a potential role for collagen in facilitating the maturation of the dermal matrix during wound healing. Levels of the proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-10 (IL-10), factors known to promote neovascularization, were substantially reduced by PaTx-II treatment. Further studies that characterize the contributions towards efficacy imparted by in vitro antimicrobial and immunomodulatory activity with PaTx-II are warranted.
Keywords	wound ; antimicrobial ; antibiotic ; PaTx-II ; fusidic acid ointment ; Australian king brown snake venom ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A brief update on potential molecular mechanisms underlying antimicrobial and wound-healing potency of snake venom molecules.

Samy, Ramar Perumal / Sethi, Gautam / Lim, Lina H K

Biochemical pharmacology

2016 Volume 115, Page(s) 1–9

Abstract: Infectious diseases remain a significant cause of morbidity and mortality worldwide. A wide range of diverse, novel classes of natural antibiotics have been isolated from different snake species in the recent past. Snake venoms contain diverse groups of ... ...

Abstract	Infectious diseases remain a significant cause of morbidity and mortality worldwide. A wide range of diverse, novel classes of natural antibiotics have been isolated from different snake species in the recent past. Snake venoms contain diverse groups of proteins with potent antibacterial activity against a wide range of human pathogens. Some snake venom molecules are pharmacologically attractive, as they possess promising broad-spectrum antibacterial activities. Furthermore, snake venom proteins (SVPs)/peptides also bind to integrins with high affinity, thereby inhibiting cell adhesion and accelerating wound healing in animal models. Thus, SVPs are a potential alternative to chemical antibiotics. The mode of action for many antibacterial peptides involves pore formation and disruption of the plasma membrane. This activity often includes modulation of nuclear factor kappa B (NF-κB) activation during skin wound healing. The NF-κB pathway negatively regulates the transforming growth factor (TGF)-β1/Smad pathway by inducing the expression of Smad7 and eventually reducing in vivo collagen production at the wound sites. In this context, SVPs that regulate the NF-κB signaling pathway may serve as potential targets for drug development.
MeSH term(s)	Animals ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/therapeutic use ; Humans ; Snake Venoms/chemistry ; Snake Venoms/therapeutic use ; Wound Healing/drug effects
Chemical Substances	Anti-Infective Agents ; Snake Venoms
Language	English
Publishing date	2016-09-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2016.03.006
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Article ; Online: Animal venoms as antimicrobial agents.

Perumal Samy, Ramar / Stiles, Bradley G / Franco, Octavio L / Sethi, Gautam / Lim, Lina H K

Biochemical pharmacology

2017 Volume 134, Page(s) 127–138

Abstract: Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. ... ...

Abstract	Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens.
MeSH term(s)	Animals ; Anti-Infective Agents/isolation & purification ; Anti-Infective Agents/pharmacology ; Drug Resistance, Multiple, Bacterial/drug effects ; Drug Resistance, Multiple, Bacterial/physiology ; Humans ; Microbial Sensitivity Tests/methods ; Venoms/isolation & purification ; Venoms/pharmacology ; Wound Healing/drug effects ; Wound Healing/physiology
Chemical Substances	Anti-Infective Agents ; Venoms
Language	English
Publishing date	2017-06-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2017.03.005
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Article ; Online: Melioidosis: Clinical impact and public health threat in the tropics.

Perumal Samy, Ramar / Stiles, Bradley G / Sethi, Gautam / Lim, Lina H K

publication RETRACTED

PLoS neglected tropical diseases

2017 Volume 11, Issue 5, Page(s) e0004738

Abstract: This review briefly summarizes the geographical distribution and clinical impact of melioidosis, especially in the tropics. Burkholderia pseudomallei (a gram-negative bacterium) is the major causative agent for melioidosis, which is prevalent in ... ...

Abstract	This review briefly summarizes the geographical distribution and clinical impact of melioidosis, especially in the tropics. Burkholderia pseudomallei (a gram-negative bacterium) is the major causative agent for melioidosis, which is prevalent in Singapore, Malaysia, Thailand, Vietnam, and Northern Australia. Melioidosis patients are increasingly being recognized in other parts of the world. The bacteria are intrinsically resistant to many antimicrobial agents, but prolonged treatment, especially with combinations of antibiotics, may be effective. Despite therapy, the overall case fatality rate of septicemia in melioidosis remains significantly high. Intracellular survival of the bacteria within macrophages may progress to chronic infections, and about 10% of patients suffer relapses. In the coming decades, melioidosis will increasingly afflict travelers throughout many global regions. Clinicians managing travelers returning from the subtropics or tropics with severe pneumonia or septicemia should consider acute melioidosis as a differential diagnosis. Patients with open skin wounds, diabetes, or chronic renal disease are at higher risk for melioidosis and should avoid direct contact with soil and standing water in endemic regions. Furthermore, there are fears that B. pseudomallei may be used as a biological weapon. Technological advancements in molecular diagnostics and antibiotic therapy are improving the disease outcomes in endemic areas throughout Asia. Research and development efforts on vaccine candidates against melioidosis are ongoing.
MeSH term(s)	Animals ; Anti-Bacterial Agents/therapeutic use ; Australia/epidemiology ; Bacterial Vaccines/therapeutic use ; Biological Warfare Agents ; Burkholderia pseudomallei/pathogenicity ; Chronic Disease ; Drug Resistance, Bacterial ; Humans ; Malaysia/epidemiology ; Melioidosis/diagnosis ; Melioidosis/epidemiology ; Melioidosis/prevention & control ; Mice ; Public Health ; Singapore/epidemiology ; Soil Microbiology ; Thailand/epidemiology ; Vietnam/epidemiology ; Virulence ; Water Microbiology
Chemical Substances	Anti-Bacterial Agents ; Bacterial Vaccines ; Biological Warfare Agents
Language	English
Publishing date	2017-05-11
Publishing country	United States
Document type	Journal Article ; Review ; Retracted Publication
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0004738
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Article ; Online: DAMPs and influenza virus infection in ageing.

Samy, Ramar Perumal / Lim, Lina H K

Ageing research reviews

2015 Volume 24, Issue Pt A, Page(s) 83–97

Abstract: Influenza A virus (IAV) is a serious global health problem worldwide due to frequent and severe outbreaks. IAV causes significant morbidity and mortality in the elderly population, due to the ineffectiveness of the vaccine and the alteration of T cell ... ...

Abstract	Influenza A virus (IAV) is a serious global health problem worldwide due to frequent and severe outbreaks. IAV causes significant morbidity and mortality in the elderly population, due to the ineffectiveness of the vaccine and the alteration of T cell immunity with ageing. The cellular and molecular link between ageing and virus infection is unclear and it is possible that damage associated molecular patterns (DAMPs) may play a role in the raised severity and susceptibility of virus infections in the elderly. DAMPs which are released from damaged cells following activation, injury or cell death can activate the immune response through the stimulation of the inflammasome through several types of receptors found on the plasma membrane, inside endosomes after endocytosis as well as in the cytosol. In this review, the detriment in the immune system during ageing and the links between influenza virus infection and ageing will be discussed. In addition, the role of DAMPs such as HMGB1 and S100/Annexin in ageing, and the enhanced morbidity and mortality to severe influenza infection in ageing will be highlighted.
MeSH term(s)	Aging/immunology ; Aging/metabolism ; Animals ; Humans ; Influenza A virus/immunology ; Influenza, Human/immunology ; Influenza, Human/metabolism ; Influenza, Human/pathology ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/metabolism ; Orthomyxoviridae Infections/pathology
Language	English
Publishing date	2015-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2015.07.005
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Article ; Online: A-kinase anchor protein 12 (AKAP12) inhibits cell migration in breast cancer.

Soh, Regina You Zhen / Lim, Jia Pei / Samy, Ramar Perumal / Chua, Pei Jou / Bay, Boon Huat

Experimental and molecular pathology

2018 Volume 105, Issue 3, Page(s) 364–370

Abstract: A-kinase anchor protein 12 (AKAP12) also known as Gravin and SSeCKS, is a novel potent scaffold protein for many key signaling factors, such as protein kinase C (PKC), PKA, cyclins as well as F-actin. AKAP12 expression is known to be suppressed in ... ...

Abstract	A-kinase anchor protein 12 (AKAP12) also known as Gravin and SSeCKS, is a novel potent scaffold protein for many key signaling factors, such as protein kinase C (PKC), PKA, cyclins as well as F-actin. AKAP12 expression is known to be suppressed in several human malignancies including breast, prostate, gastric and colon cancers. In this study, we evaluated the role of AKAP12 in the migration of breast cancer cells, an important cellular process in cancer progression. AKAP12 gene expression was analyzed in human breast cancer tissues using the Gene expression-based Outcome for Breast cancer Online (GOBO) database and TissueScan array, followed by relapse free survival (RFS) analysis with the Kaplan-Meier Plotter. AKAP12 protein was then analyzed in normal MCF10A breast cell line and six different breast cancer cell lines (AU565, Hs578T, MCF7, MDA-MB-231, T47D and ZR751). After which, siRNA-mediated knockdown of AKAP12 was carried out in MCF10A, MDA-MB-231 and Hs578T cells, followed by phenotypic assays. AKAP12 was observed to be reduced in breast cancer tissues as analyzed by GOBO and TissueScan array. Kaplan Meier survival analysis revealed that patients with AKAP12 gene expression had a higher RFS survival. There was also decreased AKAP12 protein expression in breast cancer cell lines compared to MCF10A normal epithelial breast cell line. Knockdown of AKAP12 in both MCF10A cells and Hs578T cells induced cell migration but did not alter cell proliferation. Moreover, siAKAP12 in aggressive MDA-MB-231 breast cancer cells led to an increase in cell migration. Immunofluorescence analysis of AKAP12 depleted MCF10A cells also revealed formation of thick stress fibers which could affect cell migration. Hence, the findings in this study suggest that AKAP12 is a potential metastasis suppressor in breast cancer.
MeSH term(s)	A Kinase Anchor Proteins/genetics ; A Kinase Anchor Proteins/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Movement ; Databases as Topic ; Down-Regulation ; Female ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Transcriptome
Chemical Substances	A Kinase Anchor Proteins ; AKAP12 protein, human ; Cell Cycle Proteins
Language	English
Publishing date	2018-10-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2018.10.010
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