Displaying publications 1 - 20 of 359 in total

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  1. Discovery of plant-based phytochemical as effective antivirals that target the non-structural protein C of the Nipah virus through computational methods
    Sureshan M, Prabhu D, Joshua SN, Sasikumar SV, Rajamanikandan S, Govindhapriya M, et al.
    J Biomol Struct Dyn, 2024 Apr;42(7):3568-3578.
    PMID: 37222609 DOI: 10.1080/07391102.2023.2214236
    Nipah Virus (NiV) belongs to the Paramyxoviridae family and was first identified during an outbreak in Malaysia. Some initial symptoms include mild fever, headache and sore throat, which could escalate to respiratory illness and brain inflammation. The mortality rate of NiV infection can range from 40% to 75%, which is quite high. This is mainly due to the lack of efficient drugs and vaccines. In most instances, NiV is transmitted from animals to humans. Non-Structural Proteins (C, V and W) of the Nipah virus impede the host immune response by obstructive the JAK/STAT pathway. However, Non-Structural Proteins - C (NSP-C) plays a vital role in NiV pathogenesis, which includes IFN antagonist activity and viral RNA production. In the present study, the full-length structure of NiV-NSP-C was predicted using computational modelling, and the stability of the structure was analysed using 200 ns molecular dynamic (MD) simulation. Further, the structure-based virtual screening identified five potent phytochemicals (PubChem CID: 9896047, 5885, 117678, 14887603 and 5461026) with better binding affinity against NiV-NSP-C. DFT studies clearly showed that the phytochemicals had higher chemical reactivity, and the complex MD simulation depicted that the identified inhibitors exhibited stable binding with NiV-NSP-C. Furthermore, experimental validation of these identified phytochemicals would likely control the infection of NiV.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Antiviral Agents/metabolism; Antiviral Agents/pharmacology
  2. Serum Stabilities and Antiviral Activities of Chemically Modified Peptides Against Dengue Serotypes 1-4
    Lee MF, Anasir MI, Poh CL
    J Pharm Sci, 2024 Mar;113(3):587-595.
    PMID: 38103687 DOI: 10.1016/j.xphs.2023.12.009
    Dengue presents a major public health concern in over 100 countries due to the absence of an effective vaccine and antiviral therapy against all four dengue virus (DENV) serotypes. Several antiviral peptides were previously reported to inhibit at least three or all four DENV serotypes. Chemical modifications such as d-amino acid substitutions, polyethylene glycol (PEG)ylation, and cyclization could be applied to peptides to improve their biological activities and stability in serum. The PEGylated peptide 3 (PEG-P3) was identified to be the most promising antiviral candidate as it demonstrated good inhibitory effects against all four DENV serotypes during the pre- and post-infection stages, Based on the RP-HPLC and LC/MS analysis, peptide 4 was identified to be more stable in human serum than peptide 3, with 78.9 % and 41.6 % of the peptides remaining after 72 h of incubation in human serum, respectively. Both peptides were also able to retain their antiviral activities against specific DENV serotypes after 72 h incubation in human serum. PEG-P3 was found to be more stable than the unmodified peptide 3 with 89.4 % of PEG-P3 remaining in the human serum after 72 h of incubation. PEG-P3 was able to retain its inhibitory effects against DENV-1 to 4 after 72 h of incubation in human serum. This study provided insights into the antiviral activities and stabilities of the unmodified and chemically modified peptides in human serum.
    Matched MeSH terms: Antiviral Agents/therapeutic use
  3. Assessing the impact of direct-acting antivirals on hepatitis C complications: a systematic review and meta-analysis
    Yew KC, Tan QR, Lim PC, Low WY, Lee CY
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Mar;397(3):1421-1431.
    PMID: 37728622 DOI: 10.1007/s00210-023-02716-x
    Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.
    Matched MeSH terms: Antiviral Agents/therapeutic use
  4. Fulltext Shaping the future of antiviral Treatment: Spotlight on Nucleobase-Containing drugs and their revolutionary impact
    Wong XK, Ng CS, Yeong KY
    Bioorg Chem, 2024 Mar;144:107150.
    PMID: 38309002 DOI: 10.1016/j.bioorg.2024.107150
    Nucleobases serve as essential molecular frameworks present in both natural and synthetic compounds that exhibit notable antiviral activity. Through molecular modifications, novel nucleobase-containing drugs (NCDs) have been developed, exhibiting enhanced antiviral activity against a wide range of viruses, including the recently emerged SARS‑CoV‑2. This article provides a detailed examination of the significant advancements in NCDs from 2015 till current, encompassing various aspects concerning their mechanisms of action, pharmacology and antiviral properties. Additionally, the article discusses antiviral prodrugs relevant to the scope of this review. It fills in the knowledge gap by examining the structure-activity relationship and trend of NCDs as therapeutics against a diverse range of viral diseases, either as approved drugs, clinical candidates or as early-stage development prospects. Moreover, the article highlights on the status of this field of study and addresses the prevailing limitations encountered.
    Matched MeSH terms: Antiviral Agents/pharmacology; Antiviral Agents/therapeutic use
  5. Fighting nature with nature: antiviral compounds that target retroviruses
    Siew ZY, Asudas E, Khoo CT, Cho GH, Voon K, Fang CM
    Arch Microbiol, 2024 Feb 28;206(3):130.
    PMID: 38416180 DOI: 10.1007/s00203-024-03846-3
    The human immunodeficiency virus (HIV) is a type of lentivirus that targets the human immune system and leads to acquired immunodeficiency syndrome (AIDS) at a later stage. Up to 2021, there are millions still living with HIV and many have lost their lives. To date, many anti-HIV compounds have been discovered in living organisms, especially plants and marine sponges. However, no treatment can offer a complete cure, but only suppressing it with a life-long medication, known as combined antiretroviral therapy (cART) or highly active antiretroviral therapy (HAART) which are often associated with various adverse effects. Also, it takes many years for a discovered compound to be approved for clinical use. Thus, by employing advanced technologies such as automation, conducting systematic screening and testing protocols may boost the discovery and development of potent and curative therapeutics for HIV infection/AIDS. In this review, we aim to summarize the antiretroviral therapies/compounds and their associated drawbacks since the discovery of azidothymidine. Additionally, we aim to provide an updated analysis of the most recent discoveries of promising antiretroviral candidates, along with an exploration of the current limitations within antiretroviral research. Finally, we intend to glean insightful perspectives and propose future research directions in this crucial area of study.
    Matched MeSH terms: Antiviral Agents/pharmacology; Antiviral Agents/therapeutic use
  6. Informatics and Computational Approaches for the Discovery and Optimization of Natural Product-Inspired Inhibitors of the SARS-CoV-2 2'-O-Methyltransferase
    Hanna GS, Benjamin MM, Choo YM, De R, Schinazi RF, Nielson SE, et al.
    J Nat Prod, 2024 Feb 23;87(2):217-227.
    PMID: 38242544 DOI: 10.1021/acs.jnatprod.3c00875
    The urgent need for new classes of orally available, safe, and effective antivirals─covering a breadth of emerging viruses─is evidenced by the loss of life and economic challenges created by the HIV-1 and SARS-CoV-2 pandemics. As frontline interventions, small-molecule antivirals can be deployed prophylactically or postinfection to control the initial spread of outbreaks by reducing transmissibility and symptom severity. Natural products have an impressive track record of success as prototypic antivirals and continue to provide new drugs through synthesis, medicinal chemistry, and optimization decades after discovery. Here, we demonstrate an approach using computational analysis typically used for rational drug design to identify and develop natural product-inspired antivirals. This was done with the goal of identifying natural product prototypes to aid the effort of progressing toward safe, effective, and affordable broad-spectrum inhibitors of Betacoronavirus replication by targeting the highly conserved RNA 2'-O-methyltransferase (2'-O-MTase). Machaeriols RS-1 (7) and RS-2 (8) were identified using a previously outlined informatics approach to first screen for natural product prototypes, followed by in silico-guided synthesis. Both molecules are based on a rare natural product group. The machaeriols (3-6), isolated from the genus Machaerium, endemic to Amazonia, inhibited the SARS-CoV-2 2'-O-MTase more potently than the positive control, Sinefungin (2), and in silico modeling suggests distinct molecular interactions. This report highlights the potential of computationally driven screening to leverage natural product libraries and improve the efficiency of isolation or synthetic analog development.
    Matched MeSH terms: Antiviral Agents/pharmacology
  7. Advancements in Nipah virus treatment: Analysis of current progress in vaccines, antivirals, and therapeutics
    Mishra G, Prajapat V, Nayak D
    Immunology, 2024 Feb;171(2):155-169.
    PMID: 37712243 DOI: 10.1111/imm.13695
    Nipah virus (NiV) causes severe encephalitis in humans. Three NiV strains NiV-Malaysia (NiVM ), NiV Bangladesh (NiVB ), and NiV India (NiVI reported in 2019) have been circulating in South-Asian nations. Sporadic outbreak observed in South-East Asian countries but human to human transmission raises the concern about its pandemic potential. The presence of the viral genome in reservoir bats has further confirmed that NiV has spread to the African and Australian continents. NiV research activities have gained momentum to achieve specific preparedness goals to meet any future emergency-as a result, several potential vaccine candidates have been developed and tested in a variety of animal models. Some of these candidate vaccines have entered further clinical trials. Research activities related to the discovery of therapeutic monoclonal antibodies (mAbs) have resulted in the identification of a handful of candidates capable of neutralizing the virion. However, progress in discovering potential antiviral drugs has been limited. Thus, considering NiV's pandemic potential, it is crucial to fast-track ongoing projects related to vaccine clinical trials, anti-NiV therapeutics. Here, we discuss the current progress in NiV-vaccine research and therapeutic options, including mAbs and antiviral medications.
    Matched MeSH terms: Antiviral Agents
  8. In-vitro and in-silico anti-HSV-1 activity of a marine steroid from the jellyfish Cassiopea andromeda venom
    Shamsian S, Nabipour I, Mohebbi G, Baghban N, Zare M, Zandi K, et al.
    Microb Pathog, 2024 Jan;186:106486.
    PMID: 38056601 DOI: 10.1016/j.micpath.2023.106486
    In this study, we investigated the potential in vitro anti-HSV-1 activities of the Cassiopea andromeda jellyfish tentacle extract (TE) and its fractions, as well as computational work on the thymidine kinase (TK) inhibitory activity of the identified secondary metabolites. The LD50, secondary metabolite identification, preparative and analytical chromatography, and in silico TK assessment were performed using the Spearman-Karber, GC-MS, silica gel column chromatography, RP-HPLC, LC-MS, and docking methods, respectively. The antiviral activity of TE and the two purified compounds Ca2 and Ca7 against HSV-1 in Vero cells was evaluated by MTT and RT-PCR assays. The LD50 (IV, mouse) values of TE, Ca2, and Ca7 were 104.0 ± 4, 5120 ± 14, and 197.0 ± 7 (μg/kg), respectively. They exhibited extremely effective antiviral activity against HSV-1. The CC50 and MNTD of TE, Ca2, and Ca7 were (125, 62.5), (25, 12.5), and (50, 3.125) μg/ml, respectively. GC-MS analysis of the tentacle extract revealed seven structurally distinct chemical compositions. Four of the seven compounds had a steroid structure. According to the docking results, all compounds showed binding affinity to the active sites of both thymidine kinase chains. Among them, the steroid compound Pregn-5-ene-3,11-dione, 17,20:20,21 bis [methylenebis(oxy)]-, cyclic 3-(1,2-ethane diyl acetal) (Ca2) exhibited the highest affinity for both enzyme chains, surpassing that of standard acyclovir. In silico data confirmed the experimental results. We conclude that the oxosteroid Ca2 may act as a potent agent against HSV-1.
    Matched MeSH terms: Antiviral Agents/pharmacology; Antiviral Agents/chemistry
  9. Fulltext Revolutionizing Antiviral Therapeutics: Unveiling Innovative Approaches for Enhanced Drug Efficacy
    Megantara S, Rusdin A, Budiman A, Shamsuddin S, Mohtar N, Muchtaridi M
    Int J Nanomedicine, 2024;19:2889-2915.
    PMID: 38525012 DOI: 10.2147/IJN.S447721
    Since the beginning of the coronavirus pandemic in late 2019, viral infections have become one of the top three causes of mortality worldwide. Immunization and the use of immunomodulatory drugs are effective ways to prevent and treat viral infections. However, the primary therapy for managing viral infections remains antiviral and antiretroviral medication. Unfortunately, these drugs are often limited by physicochemical constraints such as low target selectivity and poor aqueous solubility. Although several modifications have been made to enhance the physicochemical characteristics and efficacy of these drugs, there are few published studies that summarize and compare these modifications. Our review systematically synthesized and discussed antiviral drug modification reports from publications indexed in Scopus, PubMed, and Google Scholar databases. We examined various approaches that were investigated to address physicochemical issues and increase activity, including liposomes, cocrystals, solid dispersions, salt modifications, and nanoparticle drug delivery systems. We were impressed by how well each strategy addressed physicochemical issues and improved antiviral activity. In conclusion, these modifications represent a promising way to improve the physicochemical characteristics, functionality, and effectiveness of antivirals in clinical therapy.
    Matched MeSH terms: Antiviral Agents/therapeutic use
  10. Bell Palsy: Facts and Current Research Perspectives
    Rajangam J, Lakshmanan AP, Rao KU, Jayashree D, Radhakrishnan R, Roshitha B, et al.
    CNS Neurol Disord Drug Targets, 2024;23(2):203-214.
    PMID: 36959147 DOI: 10.2174/1871527322666230321120618
    Bell palsy is a non-progressive neurological condition characterized by the acute onset of ipsilateral seventh cranial nerve paralysis. People who suffer from this type of facial paralysis develop a droop on one side of their face, or sometimes both. This condition is distinguished by a sudden onset of facial paralysis accompanied by clinical features such as mild fever, postauricular pain, dysgeusia, hyperacusis, facial changes, and drooling or dry eyes. Epidemiological evidence suggests that 15 to 23 people per 100,000 are affected each year, with a recurrence rate of 12%. It could be caused by ischaemic compression of the seventh cranial nerve, which could be caused by viral inflammation. Pregnant women, people with diabetes, and people with respiratory infections are more likely to have facial paralysis than the general population. Immune, viral, and ischemic pathways are all thought to play a role in the development of Bell paralysis, but the exact cause is unknown. However, there is evidence that Bell's hereditary proclivity to cause paralysis is a public health issue that has a greater impact on patients and their families. Delay or untreated Bell paralysis may contribute to an increased risk of facial impairment, as well as a negative impact on the patient's quality of life. For management, antiviral agents such as acyclovir and valacyclovir, and steroid treatment are recommended. Thus, early diagnosis accompanied by treatment of the uncertain etiology of the disorder is crucial. This paper reviews mechanistic approaches, and emerging medical perspectives on recent developments that encounter Bell palsy disorder.
    Matched MeSH terms: Antiviral Agents/therapeutic use
  11. Fulltext Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline
    Awan AAY, Berenguer MC, Bruchfeld A, Fabrizi F, Goldberg DS, Jia J, et al.
    Ann Intern Med, 2023 Dec;176(12):1648-1655.
    PMID: 38079642 DOI: 10.7326/M23-2391
    DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO.

    METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence.

    RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

    Matched MeSH terms: Antiviral Agents/therapeutic use
  12. Fulltext Inhibition of SARS-CoV-2 3CL protease by the anti-viral chimeric protein RetroMAD1
    Chan LC, Mat Yassim AS, Ahmad Fuaad AAH, Leow TC, Sabri S, Radin Yahaya RS, et al.
    Sci Rep, 2023 Nov 17;13(1):20178.
    PMID: 37978223 DOI: 10.1038/s41598-023-47511-z
    COVID-19 results from SARS-CoV-2, which mutates frequently, challenging current treatments. Therefore, it is critical to develop new therapeutic drugs against this disease. This study explores the interaction between SARS-CoV-2 3CLpro and RetroMAD1, a well-characterized coronavirus protein and potential drug target, using in-silico methods. The analysis through the HDOCK server showed stable complex formation with a binding energy of -12.3, the lowest among reference drugs. The RetroMAD1-3CLpro complex underwent a 100 ns molecular dynamics simulation (MDS) in an explicit solvation system, generating various trajectories, including RMSD, RMSF, hydrogen bonding, radius of gyration, and ligand binding energy. MDS results confirmed intact interactions within the RetroMAD1-3CLpro complex during simulations. In vitro experiments validated RetroMAD1's ability to inhibit 3CLpro enzyme activity and prevent SARS-CoV-2 infection in human bronchial cells. RetroMAD1 exhibited antiviral efficacy comparable to Remdesivir without cytotoxicity at effective concentrations. These results suggest RetroMAD1 as a potential drug candidate against SARS-CoV-2, warranting further in vivo and clinical studies to assess its efficiency.
    Matched MeSH terms: Antiviral Agents/therapeutic use
  13. Drug repurposing for COVID-19: current evidence from randomized controlled adaptive platform trials and living systematic reviews
    Augustin Y, Staines HM, Velavan TP, Kamarulzaman A, Kremsner PG, Krishna S
    Br Med Bull, 2023 Sep 12;147(1):31-49.
    PMID: 37312588 DOI: 10.1093/bmb/ldac037
    INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally.

    SOURCES OF DATA: Recent published literature.

    AREAS OF AGREEMENT: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.

    AREAS OF CONTROVERSY: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.

    GROWING POINTS: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.

    AREAS TIMELY FOR DEVELOPING RESEARCH: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.

    Matched MeSH terms: Antiviral Agents/therapeutic use
  14. Viral hepatitis in Asia-Pacific: a post-COVID-19 reset
    Wallace J, Hamid S, Mohamed R, Wong T
    Lancet Gastroenterol Hepatol, 2023 Sep;8(9):778-780.
    PMID: 37348526 DOI: 10.1016/S2468-1253(23)00161-9
    Matched MeSH terms: Antiviral Agents/therapeutic use
  15. Fulltext Pathway to global elimination of hepatitis B: HBV cure is just the first step
    Howell J, Seaman C, Wallace J, Xiao Y, Scott N, Davies J, et al.
    Hepatology, 2023 Sep 01;78(3):976-990.
    PMID: 37125643 DOI: 10.1097/HEP.0000000000000430
    Hepatitis B (HBV) is a major cause of global morbidity and mortality, and the leading cause of liver cancer worldwide. Significant advances have recently been made toward the development of a finite HBV treatment that achieves permanent loss of HBsAg and HBV DNA (so-called "HBV cure"), which could provide the means to eliminate HBV as a public health threat. However, the HBV cure is just one step toward achieving WHO HBV elimination targets by 2030, and much work must be done now to prepare for the successful implementation of the HBV cure. In this review, we describe the required steps to rapidly scale-up future HBV cure equitably. We present key actions required for successful HBV cure implementation, integrated within the World Health Organization (WHO) Global Health Sector Strategy (GHSS) 2022-2030 framework. Finally, we highlight what can be done now to progress toward the 2030 HBV elimination targets using available tools to ensure that we are preparing, but not waiting, for the cure.
    Matched MeSH terms: Antiviral Agents/therapeutic use
  16. Fulltext Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities
    Chowdhary S, Deka R, Panda K, Kumar R, Solomon AD, Das J, et al.
    Mol Pharm, 2023 Aug 07;20(8):3698-3740.
    PMID: 37486263 DOI: 10.1021/acs.molpharmaceut.2c01080
    Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.
    Matched MeSH terms: Antiviral Agents/pharmacology; Antiviral Agents/therapeutic use
  17. Current status in cellular-based therapies for prevention and treatment of COVID-19
    Hattab D, Amer MFA, Mohd Gazzali A, Chuah LH, Bakhtiar A
    Crit Rev Clin Lab Sci, 2023 Aug;60(5):321-345.
    PMID: 36825325 DOI: 10.1080/10408363.2023.2177605
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) outbreaks that resulted in a catastrophic threat to global health, with more than 500 million cases detected and 5.5 million deaths worldwide. Patients with a COVID-19 infection presented with clinical manifestations ranging from asymptomatic to severe symptoms, resulting in acute lung injury, acute respiratory distress syndrome, and even death. Immune dysregulation through delayed innate immune response or impairment of the adaptive immune response is the key contributor to the pathophysiology of COVID-19 and SARS-CoV-2-induced cytokine storm. Symptomatic and supportive therapy is the fundamental strategy in treating COVID-19 infection, including antivirals, steroid-based therapies, and cell-based immunotherapies. Various studies reported substantial effects of immune-based therapies for patients with COVID-19 to modulate the over-activated immune system while simultaneously refining the body's ability to destroy the virus. However, challenges may arise from the complexity of the disease through the genetic variance of the virus itself and patient heterogeneity, causing increased transmissibility and heightened immune system evasion that rapidly change the intervention and prevention measures for SARS-CoV-2. Cell-based therapy, utilizing stem cells, dendritic cells, natural killer cells, and T cells, among others, are being extensively explored as other potential immunological approaches for preventing and treating SARS-CoV-2-affected patients the similar process was effectively proven in SARS-CoV-1 and MERS-CoV infections. This review provides detailed insights into the innate and adaptive immune response-mediated cell-based immunotherapies in COVID-19 patients. The immune response linking towards engineered autologous or allogenic immune cells for either treatment or preventive therapies is subsequently highlighted in an individual study or in combination with several existing treatments. Up-to-date data on completed and ongoing clinical trials of cell-based agents for preventing or treating COVID-19 are also outlined to provide a guide that can help in treatment decisions and future trials.
    Matched MeSH terms: Antiviral Agents/therapeutic use
  18. Fulltext COVID-19 Therapeutic Potential of Natural Products
    Low Z, Lani R, Tiong V, Poh C, AbuBakar S, Hassandarvish P
    Int J Mol Sci, 2023 May 31;24(11).
    PMID: 37298539 DOI: 10.3390/ijms24119589
    Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.
    Matched MeSH terms: Antiviral Agents/pharmacology; Antiviral Agents/therapeutic use
  19. Fulltext Viral Protein Accumulation of Zika Virus Variants Links with Regulation of Innate Immunity for Differential Control of Viral Replication, Spread, and Response to Interferon
    Lu AY, Gustin A, Newhouse D, Gale M
    J Virol, 2023 May 31;97(5):e0198222.
    PMID: 37162358 DOI: 10.1128/jvi.01982-22
    Asian lineage Zika virus (ZIKV) strains emerged globally, causing outbreaks linked with critical clinical disease outcomes unless the virus is effectively restricted by host immunity. We have previously shown that retinoic acid-inducible gene-I (RIG-I) senses ZIKV to trigger innate immunity to direct interferon (IFN) production and antiviral responses that can control ZIKV infection. However, ZIKV proteins have been demonstrated to antagonize IFN. Here, we conducted in vitro analyses to assess how divergent prototypic ZIKV variants differ in virologic properties, innate immune regulation, and infection outcome. We comparatively assessed African lineage ZIKV/Dakar/1984/ArD41519 (ZIKV/Dakar) and Asian lineage ZIKV/Malaysia/1966/P6740 (ZIKV/Malaysia) in a human epithelial cell infection model. De novo viral sequence determination identified amino acid changes within the ZIKV/Dakar genome compared to ZIKV/Malaysia. Viral growth analyses revealed that ZIKV/Malaysia accumulated viral proteins and genome copies earlier and to higher levels than ZIKV/Dakar. Both ZIKV strains activated RIG-I/IFN regulatory factor (IRF3) and NF-κB pathways to induce inflammatory cytokine expression and types I and III IFNs. However, ZIKV/Malaysia, but not ZIKV/Dakar, potently blocked downstream IFN signaling. Remarkably, ZIKV/Dakar protein accumulation and genome replication were rescued in RIG-I knockout (KO) cells late in acute infection, resulting in ZIKV/Dakar-mediated blockade of IFN signaling. We found that RIG-I signaling specifically restricts viral protein accumulation late in acute infection where early accumulation of viral proteins in infected cells confers enhanced ability to limit IFN signaling, promoting viral replication and spread. Our results demonstrate that RIG-I-mediated innate immune signaling imparts restriction of ZIKV protein accumulation, which permits IFN signaling and antiviral actions controlling ZIKV infection. IMPORTANCE ZIKV isolates are classified under African or Asian lineages. Infection with emerging Asian lineage-derived ZIKV strains is associated with increased incidence of neurological symptoms that were not previously reported during infection with African or preemergent Asian lineage viruses. In this study, we utilized in vitro models to compare the virologic properties of and innate immune responses to two prototypic ZIKV strains from distinct lineages: African lineage ZIKV/Dakar and Asian lineage ZIKV/Malaysia. Compared to ZIKV/Dakar, ZIKV/Malaysia accumulates viral proteins earlier, replicates to higher levels, and robustly blocks IFN signaling during acute infection. Early accumulation of ZIKV/Malaysia NS5 protein confers enhanced ability to antagonize IFN signaling, dampening innate immune responses to promote viral spread. Our data identify the kinetics of viral protein accumulation as a major regulator of host innate immunity, influencing host-mediated control of ZIKV replication and spread. Importantly, these findings provide a novel framework for evaluating the virulence of emerging variants.
    Matched MeSH terms: Antiviral Agents/pharmacology
  20. Fulltext Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections
    Loo CY, Lee WH, Zhou QT
    Pharm Res, 2023 May;40(5):1015-1036.
    PMID: 37186073 DOI: 10.1007/s11095-023-03520-1
    With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents (e.g. ribavirin, palivizumab and valaciclovir) have been successfully developed for the treatment of respiratory virus infections such as influenza, respiratory syncytial virus and SARS-CoV-2 infections. These therapeutics are conventionally delivered via oral, intramuscular or injection route and are associated with several adverse events due to systemic toxicity. The inherent in vivo instability of biological therapeutics may hinder them from being administered without proper formulations. Therefore, we have witnessed a boom in nanotechnology coupled with a needle-free administration approach such as the inhalation route for the delivery of complex therapeutics to treat respiratory infections. This review discussed the recent advances in the inhalation strategies of nanoformulations that target virus respiratory infections.
    Matched MeSH terms: Antiviral Agents/therapeutic use
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