Displaying publications 1 - 20 of 53 in total

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  1. Wong CY, Cheong SK, Mok PL, Leong CF
    Pathology, 2008 Jan;40(1):52-7.
    PMID: 18038316
    AIMS: Adult human bone marrow contains a population of mesenchymal stem cells (MSC) that contributes to the regeneration of tissues such as bone, cartilage, muscle, tendon, and fat. In recent years, it has been shown that functional stem cells exist in the adult bone marrow, and they can contribute to renal remodelling or reconstitution of injured renal glomeruli, especially mesangial cells. The purpose of this study is to examine the ability of MSC isolated from human bone marrow to differentiate into mesangial cells in glomerular injured athymic mice.

    METHODS: MSC were isolated from human bone marrow mononuclear cells based on plastic adherent properties and expanded in vitro in the culture medium. Human mesenchymal stem cells (hMSC) were characterised using microscopy, immunophenotyping, and their ability to differentiate into adipocytes, chondrocytes, and osteocytes. hMSC were then injected into athymic mice, which had induced glomerulonephropathy (GN).

    RESULTS: Test mice (induced GN and infused hMSC) were shown to have anti-human CD105(+) cells present in the kidneys and were also positive to anti-human desmin, a marker for mesangial cells. Furthermore, immunofluorescence assays also demonstrated that anti-human desmin(+) cells in the glomeruli of these test mice were in the proliferation stage, being positive to anti-human Ki-67.

    CONCLUSIONS: These findings indicate that hMSC found in renal glomeruli differentiated into mesangial cells in vivo after glomerular injury occurred.

  2. Tong JB, Sanjiv R, Elderdery A, Wu X, Rajesh R, Suresh Kumar S, et al.
    Med J Malaysia, 2023 Jul;78(4):534-540.
    PMID: 37518929
    INTRODUCTION: The meniscus plays an important role in maintaining homeostasis to facilitate the normal function of the knee joint. It is one of the most commonly injured areas of the knee joint. Meniscal-related injuries can lead to significantly decreased athletic ability, and their incidence has increased yearly. It has been found that most meniscal injuries are irreparable, and meniscectomy can increase the predisposition to knee osteoarthritis. Tissue engineering technology on meniscus repairing and transplantation has received widespread attention recently. This review aimed to analyse the scientific literature regarding the potential applications of tissue engineering on meniscus repairing and transplantation procedures.

    METHOD AND MATERIALS: The electronic search was carried out using PubMed/MEDLINEⓇdatabases with the keywords "tissue engineering AND meniscus" spanning the period of publications from Jan 1980 until Dec 2022.

    RESULTS: The literature search identified 405 references in PubMed/MEDLINE, and 179 were selected following the eligibility requirements. The research analysis showed that the existing meniscal tissue engineering studies used a wide variety of seed cells, cytokines, bioactive materials and 3D structures. Each showed distinct advantages and disadvantages in terms of biocompatibility, degradability, mechanical strength, porosity, and etc. It was noted that 3D printing technology is promising for tissue engineering meniscus research. In addition, the optimal use of compression and hydrostatic pressure to markedly improve the functional properties of tissue-engineering meniscal can serve as an useful strategy.

    CONCLUSION: This review analysed the different approaches employed for meniscus tissue engineering and regeneration. Meniscal tissue engineering still faces several major challenges in terms of seed cells, choice of materials and 3D printing strategies, which should be effectively overcome to harness the full potential of this technology.

  3. Teh SW, Koh AE, Tong JB, Wu X, Samrot AV, Rampal S, et al.
    Front Cell Dev Biol, 2021;9:634131.
    PMID: 34490233 DOI: 10.3389/fcell.2021.634131
    Bone fractures have a high degree of severity. This is usually a result of the physical trauma of diseases that affect bone tissues, such as osteoporosis. Due to its highly vascular nature, the bone is in a constant state of remodeling. Although those of younger ages possess bones with high regenerative potential, the impact of a disrupted vasculature can severely affect the recovery process and cause osteonecrosis. This is commonly seen in the neck of femur, scaphoid, and talus bone. In recent years, mesenchymal stem cell (MSC) therapy has been used to aid in the regeneration of afflicted bone. However, the cut-off in blood supply due to bone fractures can lead to hypoxia-induced changes in engrafted MSCs. Researchers have designed several oxygen-generating biomaterials and yielded varying degrees of success in enhancing tissue salvage and preserving cellular metabolism under ischemia. These can be utilized to further improve stem cell therapy for bone repair. In this review, we touch on the pathophysiology of these bone fractures and review the application of oxygen-generating biomaterials to further enhance MSC-mediated repair of fractures in the three aforementioned parts of the bone.
  4. Teh SW, Mok PL, Abd Rashid M, Bastion MC, Ibrahim N, Higuchi A, et al.
    Int J Mol Sci, 2018 Feb 13;19(2).
    PMID: 29438279 DOI: 10.3390/ijms19020558
    Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.
  5. Teh SW, Elderdery A, Rampal S, Subbiah SK, Mok PL
    Contemp Oncol (Pozn), 2023;27(4):255-262.
    PMID: 38405210 DOI: 10.5114/wo.2023.135364
    INTRODUCTION: Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin malignancy, representing around 20% of all skin cancers. It is the main cause of death due to non-melanoma skin cancer every year. Metastatic cutaneous SCC is associated with poor prognosis in patients and warrants a more effective and specific approach such as disruption of genes associated with cancer metastasis.

    MATERIAL AND METHODS: Matrix metalloproteinases (MMPs) are enzymes involved in cancer progression and are regarded as major oncotargets. Among others, MMP9 plays critical roles in tumour progression, angiogenesis, and invasion of cutaneous SCC. We aimed to determine whether the MMP9 gene is a suitable gene target for anti-cancer therapy for cutaneous SCC. We performed clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 transfection of guide RNA (gRNA) targeting the MMP9 gene into human cutaneous SCC cell line A431.

    RESULTS: Following CRISPR transfection treatment, the viability (p < 0.01) and migratory activities (p < 0.0001) of in vitro cutaneous SCC cells were found to be reduced significantly. The use of quantitative polymerase chain reaction (qPCR) also revealed downregulation of the mRNA expression levels of cancer-promoting genes TGF-β, FGF, PI3K, VEGF-A, and vimentin. Direct inhibition of the MMP9 gene was shown to decrease survivability and metastasis of cutaneous SCC cell line A431.

    CONCLUSIONS: Our findings provided direct evidence that MMP9 is important in the viability, proliferation, and metastasis of cutaneous SCC cells. It serves as a positive foundation for future CRISPR-based targeted anti-cancer therapies in treating skin cancer and other forms of malignancies that involve MMPs as the key determinants.

  6. Sivan PP, Syed S, Mok PL, Higuchi A, Murugan K, Alarfaj AA, et al.
    Stem Cells Int, 2016;2016:8304879.
    PMID: 27293447 DOI: 10.1155/2016/8304879
    Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.
  7. Shirley Ding SL, Leow SN, Munisvaradass R, Koh EH, Bastion ML, Then KY, et al.
    Eye (Lond), 2016 Oct;30(10):1293-1309.
    PMID: 27285322 DOI: 10.1038/eye.2016.94
    Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions.
  8. Satar NA, Fakiruddin KS, Lim MN, Mok PL, Zakaria N, Fakharuzi NA, et al.
    Oncol Rep, 2018 Aug;40(2):669-681.
    PMID: 29845263 DOI: 10.3892/or.2018.6461
    Through the specific identification and direct targeting of cancer stem cells (CSCs), it is believed that a better treatment efficacy of cancer may be achieved. Hence, the present study aimed to identify a CSC subpopulation from adenocarcinoma cells (A549) as a model of non‑small cell lung cancer (NSCLC). Ιnitially, we sorted two subpopulations known as the triple‑positive (EpCAM+/CD166+/CD44+) and triple‑negative (EpCAM-/CD166-/CD44-) subpopulation using fluorescence-activated cell sorting (FACS). Sorted cells were subsequently evaluated for proliferation and chemotherapy-resistance using a viability assay and were further characterized for their clonal heterogeneity, self-renewal characteristics, cellular migration, alkaline dehydrogenase (ALDH) activity and the expression of stemness-related genes. According to our findings the triple‑positive subpopulation revealed significantly higher (P<0.01) proliferation activity, exhibited better clonogenicity, was mostly comprised of holoclones and had markedly bigger (P<0.001) spheroid formation indicating a better self-renewal capacity. A relatively higher resistance to both 5‑fluouracil and cisplatin with 80% expression of ALDH was observed in the triple‑positive subpopulation, compared to only 67% detected in the triple‑negative subpopulation indicated that high ALDH activity contributed to greater chemotherapy-resistance characteristics. Higher percentage of migrated cells was observed in the triple‑positive subpopulation with 56% cellular migration being detected, compared to only 19% in the triple‑negative subpopulation on day 2. This was similarly observed on day 3 in the triple‑positive subpopulation with 36% higher cellular migration compared to the triple‑negative subpopulation. Consistently, elevated levels of the stem cell genes such as REX1 and SSEA4 were also found in the triple‑positive subpopulation indicating that the subpopulation displayed a strong characteristic of pluripotency. In conclusion, our study revealed that the triple‑positive subpopulation demonstrated similar characteristics to CSCs compared to the triple‑negative subpopulation. It also confirmed the feasibility of using the triple‑positive (EpCAM+/CD166+/CD44+) marker as a novel candidate marker that may lead to the development of novel therapies targeting CSCs of NSCLC.
  9. Samrot AV, Sean TC, Bhavya KS, Sahithya CS, Chan-Drasekaran S, Palanisamy R, et al.
    Pathogens, 2021 Feb 01;10(2).
    PMID: 33535649 DOI: 10.3390/pathogens10020145
    Leptospirosis is a perplexing conundrum for many. In the existing literature, the pathophysiological mechanisms pertaining to leptospirosis is still not understood in full. Considered as a neglected tropical zoonotic disease, leptospirosis is culminating as a serious problem worldwide, seemingly existing as co-infections with various other unrelated diseases, including dengue and malaria. Misdiagnosis is also common as non-specific symptoms are documented extensively in the literature. This can easily lead to death, as the severe form of leptospirosis (Weil's disease) manifests as a complex of systemic complications, especially renal failure. The virulence of Leptospira sp. is usually attributed to the outer membrane proteins, including LipL32. With an armament of virulence factors at their disposal, their ability to easily adhere, invade and replicate within cells calls for a swift refinement in research progress to establish their exact pathophysiological framework. As an effort to reconstitute the current knowledge on leptospirosis, the basis of leptospiral infection, including its risk factors, classification, morphology, transmission, pathogenesis, co-infections and clinical manifestations are highlighted in this review. The various diagnostic techniques are also outlined with emphasis on their respective pros and cons.
  10. Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.
    Front Cell Dev Biol, 2021;9:637270.
    PMID: 34291043 DOI: 10.3389/fcell.2021.637270
    Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.
  11. Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.
    Front Cell Dev Biol, 2021;9:800659.
    PMID: 35178398 DOI: 10.3389/fcell.2021.800659
    [This corrects the article DOI: 10.3389/fcell.2021.637270.].
  12. Rayzah M, Elderdery AY, Alzerwi NAN, Alzahrani B, Alsrhani A, Alsultan A, et al.
    Plants (Basel), 2023 Sep 05;12(18).
    PMID: 37765338 DOI: 10.3390/plants12183174
    An aqueous extract of Syzygium cumini seeds was utilized to green synthesize titanium dioxide nanoparticles (TiO2 NPs). UV-Visible, DLS, FTIR, XRD, FESEM, TEM, SAED, EDAX, and photoluminescence spectroscopy techniques were employed to characterize the prepared TiO2 nanoparticles. The rutile crystal structure of TiO2 NPs was revealed by XRD study. The TEM and FESEM images of the TiO2 NPs revealed an average particle size of 50-100 nm. We employed EDAX to investigate the elemental compositions of TiO2 NPs. The O-Ti-O stretching bands appeared in the FTIR spectrum of TiO2 NPs at wavenumbers of 495 cm-1. The absorption edge peaks of TiO2 NPs were found in the UV-vis spectra at 397 nm. The MTT study revealed that TiO2 NPs effectively inhibited the growth of liver cancer Hep3 and Hep-G2 cells. The results of the corresponding fluorescent staining assays showed that TiO2 NPs significantly increased ROS generation, decreased MMP, and induced apoptosis in both liver cancer Hep3 and Hep-G2 cells. TiO2 nanoparticles lessened SOD, CAT, and GSH levels while augmenting MDA contents in Hep3 and Hep-G2 cells. In both Hep3 and Hep-G2 cells treated with TiO2 NPs, the Bax, CytC, p53, caspase-3, -8, and -9 expressions were remarkably augmented, while Bcl-2 expression was reduced. Overall, these findings revealed that formulated TiO2 NPs treatment considerably inhibited growth and triggered apoptosis in Hep3 and HepG2 cells.
  13. Munisvaradass R, Kumar S, Govindasamy C, Alnumair KS, Mok PL
    Int J Mol Sci, 2017 Sep 08;18(9).
    PMID: 28885562 DOI: 10.3390/ijms18091797
    Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non-transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours.
  14. Mok PL, Leong CF, Cheong SK
    Malays J Pathol, 2013 Jun;35(1):17-32.
    PMID: 23817392 MyJurnal
    Mesenchymal stem cells (MSC) are multipotent, self-renewing cells that can be found mainly in the bone marrow, and other post-natal organs and tissues. The ease of isolation and expansion, together with the immunomodulatory properties and their capability to migrate to sites of inflammation and tumours make them a suitable candidate for therapeutic use in the clinical settings. We review here the cellular mechanisms underlying the emerging applications of MSC in various fields.
  15. Mok PL, Cheong SK, Leong CF, Chua KH, Ainoon O
    Tissue Cell, 2012 Aug;44(4):249-56.
    PMID: 22560724 DOI: 10.1016/j.tice.2012.04.002
    Mesenchymal stromal cells (MSC) are an attractive cell-targeting vehicle for gene delivery. MIDGE (an acronym for Minimalistic, Immunologically Defined Gene Expression) construct is relatively safer than the viral or plasmid expression system as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. The objective of this study was to test the ability of the human MSC (hMSC) to deliver the erythropoietin (EPO) gene in a nude mice model following nucleofection using a MIDGE construct. hMSC nucleofected with MIDGE encoding the EPO gene was injected subcutaneously in Matrigel at the dorsal flank of nude mice. Subcutaneous implantation of nucleofected hMSC resulted in increased hemoglobin level with presence of human EPO in the peripheral blood of the injected nude mice in the first two weeks post-implantation compared with the control groups. The basal layer of the hair shaft in the dermal layer was found to be significantly positive for immunohistochemical staining of a human EPO antibody. However, only a few basal layers of the hair shaft were found to be positively stained for CD105. In conclusion, hMSC harboring MIDGE-EPO could deliver and transiently express the EPO gene in the nude mice model. These cells could be localized to the hair follicle and secreted EPO protein might have possible role in hair regeneration.
  16. Mok PL, Cheong SK, Leong CF, Chua KH, Ainoon O
    Cytotechnology, 2012 Mar;64(2):203-16.
    PMID: 22160354 DOI: 10.1007/s10616-011-9413-2
    Human mesenchymal stromal cell (hMSC) is a potential target for cell and gene therapy-based approaches against a variety of different diseases. Whilst cationic lipofection has been widely experimented, the Nucleofector technology is a relatively new non-viral transfection method designed for primary cells and hard-to-transfect cell lines. Herein, we compared the efficiency and viability of nucleofection with cationic lipofection, and used the more efficient transfection method, nucleofection, to deliver a construct of minimalistic, immunologically defined gene expression encoding the erythropoietin (MIDGE-EPO) into hMSC. MIDGE construct is relatively safer than the viral and plasmid expression systems as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. Using a plasmid encoding the luciferase gene, we demonstrated a high transfection efficiency using the U-23 (21.79 ± 1.09%) and C-17 (5.62 ± 1.09%) pulsing program in nucleofection. The cell viabilities were (44.93 ± 10.10)% and (21.93 ± 5.72)%, respectively 24 h post-nucleofection. On the other hand, lipofection treatment only yielded less than 0.6% efficiencies despite showing higher viabilities. Nucleofection did not affect hMSC renewability, immunophenotype and differentiation potentials. Subsequently, we nucleofected MIDGE-EPO using the U-23 pulsing program into hMSC. The results showed that, despite a low nucleofection efficiency with this construct, the EPO protein was stably expressed in the nucleofected cells up to 55 days when determined by ELISA or immunocytochemical staining. In conclusion, nucleofection is an efficient non-viral transfection approach for hMSC, which when used in conjunction with a MIDGE construct, could result in extended and stable transgene expression in hMSC.
  17. Mok PL, Cheong SK, Leong CF
    Malays J Pathol, 2008 Jun;30(1):11-9.
    PMID: 19108406 MyJurnal
    Mesenchymal stem cells are pluripotent progenitors that could be found in human bone marrow. Mesenchymal stem cells are capable of renewing themselves without differentiation in long-term culture. These cells also have low immunogenicity and can suppress alloreactive T cell responses. In the current study, mesenchymal stem cells isolated and propagated previously from the bone marrow of a megaloblastic anaemia patient were tested for their capabilities to differentiate into adipocytes, chondrocytes and osteoblasts in vitro. The differentiated cells were determined by Oil Red O, Alcian Blue-PAS and Alizarin Red S staining, and reverse transcriptase-polymerase chain reaction to determine the expression of mRNA specific for adipogenesis, chondrogenesis and osteogenesis. The results showed that the fibroblast-like cells were capable of differentiating into adipocytes, chondrocytes and osteoblasts upon chemical induction. The adipocytes, chondrocytes and osteoblasts were stained positively to Oil Red O, Alcian Blue-PAS and Alizarin Red S respectively. The differentiated cells were also found to express mRNA specific for adipogenesis ('peroxisome proliferation-activated receptor gamma2' and lipoprotein lipase), chondrogenesis (collagen type II) and osteogenesis (osteocalcin, osteopontin and alkaline phosphatase). In conclusion, this research has successfully isolated fibroblast-like cells from human bone marrow and these cells demonstrated morphological, cytochemical and immunochemical characteristics similar to mesenchymal stem cells. These cells maintain their proliferative properties and could be differentiated into the mesoderm lineage. The success of this study is vital because mesenchymal stem cells can be used in cellular therapy to regenerate or replace damaged tissues, or as a vehicle for therapeutic gene delivery in the future.
  18. Mok PL, Cheong SK, Leong CF, Othman A
    Cytotherapy, 2008;10(2):116-24.
    PMID: 18368590 DOI: 10.1080/14653240701816996
    Mesenchymal stromal cells (MSC) are pluripotent progenitor cells that can be found in human bone marrow (BM). These cells have low immunogenicity and could suppress alloreactive T-cell responses. In the current study, MSC were tested for their capacity to carry and deliver the erythropoietin (EPO) gene in vitro.
  19. Mok PL, Koh AE, Farhana A, Alsrhani A, Alam MK, Suresh Kumar S
    Saudi J Biol Sci, 2021 Apr;28(4):2502-2509.
    PMID: 33551661 DOI: 10.1016/j.sjbs.2021.01.051
    COVID-19 is a rapidly emerging infectious disease caused by the SARS-CoV-2 virus currently spreading throughout the world. To date, there are no specific drugs formulated for it, and researchers around the globe are racing against the clock to investigate potential drug candidates. The repurposing of existing drugs in the market represents an effective and economical strategy commonly utilized in such investigations. In this study, we used a multiple-sequence alignment approach for preliminary screening of commercially-available drugs on SARS-CoV sequences from the Kingdom of Saudi Arabia (KSA) isolates. The viral genomic sequences from KSA isolates were obtained from GISAID, an open access repository housing a wide variety of epidemic and pandemic virus data. A phylogenetic analysis of the present 164 sequences from the KSA provinces was carried out using the MEGA X software, which displayed high similarity (around 98%). The sequence was then analyzed using the VIGOR4 genome annotator to construct its genomic structure. Screening of existing drugs was carried out by mining data based on viral gene expressions from the ZINC database. A total of 73 hits were generated. The viral target orthologs were mapped to the SARS-CoV-2 KSA isolate sequence by multiple sequence alignment using CLUSTAL OMEGA, and a list of 29 orthologs with purchasable drug information was generated. The results showed that the SARS CoV replicase polyprotein 1a had the highest sequence similarity at 79.91%. Through ZINC data mining, tanshinones were found to have high binding affinities to this target. These compounds could be ideal candidates for SARS-CoV-2. Other matches ranged between 27 and 52%. The results of this study would serve as a significant endeavor towards drug discovery that would increase our chances of finding an effective treatment or prevention against COVID19.
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