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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
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
Fulltext Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis

Chan Y, Ng SW, Mehta M, Anand K, Kumar Singh S, Gupta G, et al.

Med Hypotheses, 2020 Nov;144:110298.
PMID: 33254489 DOI: 10.1016/j.mehy.2020.110298

Outbreaks of influenza infections in the past have severely impacted global health and socioeconomic growth. Antivirals and vaccines are remarkable medical innovations that have been successful in reducing the rates of morbidity and mortality from this disease. However, the relentless emergence of drug resistance has led to a worrisome increase in the trend of influenza outbreaks, characterized by worsened clinical outcomes as well as increased economic burden. This has prompted the need for breakthrough innovations that can effectively manage influenza outbreaks. This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections.

Matched MeSH terms: Antiviral Agents/therapeutic use
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/therapeutic use
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
Nipah and Hendra virus infectious diseases

Yoneda M

Nippon Rinsho, 2016 12;74(12):1973-1978.
PMID: 30550652

Nipah and Hendra virus were first identified in mid 1990s in Australia and Malaysia, caus- ing epidemics with high mortality rate in affected animals and humans. Since their first emer- gence, they continued to re-emerge in Australia and South East Asia almost every year. Nipah and Hendra virus were classified in the new genus Henipavirus because of their un- common features amongst Paramyxoviridae. Henipaviruses are zoonotic paramyxoviruses with a broad tropism, and cause severe acute respiratory disease and encephalitis. Their high virulence and wide host range make them to be given Biosecurity Level 4 status. This review summarizes details of Henipavirus emergence, reservoir hosts and pathology, and introduce recent progress in vaccines and antivirals.

Matched MeSH terms: Antiviral Agents/therapeutic use
Systematic review on current antiviral therapy in COVID-19 pandemic

Perveen RA, Nasir M, Talha KA, Selina F, Islam MA

Med J Malaysia, 2020 11;75(6):710-716.
PMID: 33219182

INTRODUCTION: Currently, there are several attempts to find an effective antiviral drugs against the COVID-19. Although majority of the COVID-19 patients have mild to moderate clinical events, up to 5-10% may have severe, life threatening events that urgently require effective drugs. The purpose of this systematic review is to evaluate the effectiveness of antiviral therapies in the treatment of COVID-19.
METHODS: An extensive search was performed in PubMed, EMBASE, Cochrane Library for randomised controlled trials (RCTs), prospective case series studies that evaluated therapies COVID-19. The outcomes searched for were mortality, recovery rate, length of hospital stay and clinical improvement from January to May 15, 2020. Independent reviewers searched, identified, screened, and related studies were included.
RESULTS: Total of five RCTs on 439 patients and seventeen case series involving 1656 patients were found in the specified review period that reported the use of Lopinavir, Ritonavir, Remdesivir. Oseltamivir, Ribavirin in patients with COVID-19; but none of which showed efficacy of antiviral therapy. Such current findings impede researchers from recommending an appropriate and effective antiviral therapy against COVID-19, making it a serious concern for the global community.
DISCUSSION: In the present pandemic and any future epidemics, all the related authorities should pursue many more RCTs, cohort and case series for a prospective outcome in the management and treatment guidelines.

Matched MeSH terms: Antiviral Agents/therapeutic use
Synthetic and Semi-synthetic Drugs as a Promising Therapeutic Option for the Treatment of COVID-19

Shirbhate E, Patel P, Patel VK, Veerasamy R, Sharma PC, Sinha BN, et al.

Mini Rev Med Chem, 2021;21(8):1004-1016.
PMID: 33280595 DOI: 10.2174/1389557520666201204162103

The novel coronavirus disease-19 (COVID-19) is a global pandemic that emerged from Wuhan, China, and has spread all around the world, affecting 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 updates of August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine exists. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID- 19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in clinical uses or studies on COVID-19 and also focuses on the mode of action of drugs being repositioned against COVID-19.

Matched MeSH terms: Antiviral Agents/therapeutic use*
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
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/therapeutic use
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
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

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