|
1
|
Darvishi M, Amiri R, Ghannad E, Mehrabkhani S, Rastgar N, Razaghi M, Bansal J, Chahar M, Rajput P, Saffarfar H, Ali-Khiavi P, Mobed A, Yazdani Y. Nanodiagnostics in global eradication of hepatitis C virus. Clin Chim Acta 2025; 565:120013. [PMID: 39447823 DOI: 10.1016/j.cca.2024.120013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/20/2024] [Accepted: 10/20/2024] [Indexed: 10/26/2024]
Abstract
Hepatitis C, caused by the hepatitis C virus (HCV), is a prevalent liver disease with severe outcomes, including cirrhosis and hepatocellular carcinoma. Traditional diagnostic methods primarily detect antiviral antibodies (anti-HCV) or viral RNA, but these approaches have limitations. Anti-HCV antibodies may take 2-4 weeks to develop in acute cases and can be absent in some individuals, leading to undiagnosed early-stage infections. This poses significant challenges for public health, particularly in resource-limited settings where early detection is crucial. This article explores the development of biosensors engineered to directly detect HCV surface antigens, such as envelope proteins. These biosensors provide a promising solution for earlier and more accurate diagnosis by identifying viral components at the initial stages of infection. By focusing on direct detection of viral antigens, these innovations could enhance early diagnosis, facilitate timely intervention, and reduce virus transmission. We evaluate the advancements in biosensor technology over the past decade and their potential to improve HCV detection in clinical and field settings, ultimately supporting global efforts to eliminate HCV as a public health threat.
Collapse
Affiliation(s)
- Mohammad Darvishi
- Darvishi M. Associate Professor of Infectious Disease, School of Aerospace and Subaquatic Medicine, Infectious Diseases & Tropical Medicine Research Center (IDTMC), AJA University of Medical Sciences, Tehran, Iran
| | - Reza Amiri
- Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
| | - Emad Ghannad
- Faculty of Pharmacy, Guilan University of Medical Sciences
| | - Samir Mehrabkhani
- Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
| | - Nassim Rastgar
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahkameh Razaghi
- Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences
| | - Jaya Bansal
- Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjeri, Mohali 140307, Punjab, India
| | - Mamata Chahar
- Department of Chemistry, NIMS Institute of Engineering & Technology, NIMS University Rajasthan, Jaipur, India
| | - Pranchal Rajput
- School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India
| | - Hossein Saffarfar
- Cardiovascular Research Center, Tehran, Tehran University of Medical Sciences, Tehran, Iran
| | - Payam Ali-Khiavi
- Medical faculty, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmad Mobed
- Social Determinants of Health Research Center, Health Management and Safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Yalda Yazdani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
|
2
|
Samma AA, Ko CK, Sahra M, Fitrayani N, Thios FV, Permana AD. Validation of spectrophotometric and colorimetric method for the specific quantification of sofosbuvir From luminar capsule microneedle in liver tissue through ex vivo and in vivo applications. ANNALES PHARMACEUTIQUES FRANÇAISES 2024:S0003-4509(24)00170-6. [PMID: 39613187 DOI: 10.1016/j.pharma.2024.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 11/22/2024] [Accepted: 11/23/2024] [Indexed: 12/01/2024]
Abstract
An antiviral prodrug that has received regulatory approval and primarily employed in the treatment of hepatitis C is sofosbuvir (SOF). It is therefore imperative to develop advanced delivery methods for SOF in order to address existing absor ption issue and maximize the efficacy. In this study, we developed microneedle-integrated SOF (MN-SOF) which were elongated with branches and coated capsules to form luminar capsule microneedles (LUCAMs). To facilitate the formulation of LUCAMs, analytical methods for SOF in ethanol, artificial intestinal fluid (AIF), and artificial gastric fluid (AGF) were developed using a UV-vis spectrophotometer and colorimetric techniques in liver tissue. These methods were validated by combi ning the samples with ammonium metavanadate reagent. The validation process was conducted in order to ensure the accuracy, precision, linearity, specificity, and sensitivity of the methods. These methods exhibited a correlation coefficient of 0.9999, with a coefficient of variation below 25%. The methods demonstrate high accuracy and precision, with relative standard deviation (RSD) values ranging from 0.67% to 9.42% across different medium. The limit of detection (LOD) and limit of quantification (LOQ) values of SOF on each calibration curve of ethanol, artificial gastric fluid (AGF), artificial intestinal fluid (AIF), and rabbit liver tissue are 0.54μg/mL and 1.65μg/mL; 0.54μg/mL and 1.64μg/mL; 0.39μg/mL and 1.21μg/mL; 0.27μg/mL and 0.83μg/mL. As a significant outcome, the analytical method was validated and demonstrated suitability for determining the amount of SOF in the LUCAMs formulation through in vitro solubility, ex vivo permeation profiles, and in vivo drug delivery studies.
Collapse
Affiliation(s)
- Abigael Alik Samma
- Faculty of Pharmacy, Hasanuddin University, Makassar, 90245 South Sulawesi, Indonesia
| | - Christopher Kosasi Ko
- Faculty of Pharmacy, Hasanuddin University, Makassar, 90245 South Sulawesi, Indonesia
| | - Musyfira Sahra
- Faculty of Pharmacy, Hasanuddin University, Makassar, 90245 South Sulawesi, Indonesia
| | - Nurul Fitrayani
- Faculty of Pharmacy, Hasanuddin University, Makassar, 90245 South Sulawesi, Indonesia
| | | | - Andi Dian Permana
- Faculty of Pharmacy, Hasanuddin University, Makassar, 90245 South Sulawesi, Indonesia.
| |
Collapse
|
|
3
|
McSteen BW, Ying XH, Lucero C, Jesudian AB. Viral etiologies of acute liver failure. World J Virol 2024; 13:97973. [PMID: 39323454 PMCID: PMC11401000 DOI: 10.5501/wjv.v13.i3.97973] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/07/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024] Open
Abstract
Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.
Collapse
Affiliation(s)
- Brian W McSteen
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Xiao-Han Ying
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Catherine Lucero
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| | - Arun B Jesudian
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| |
Collapse
|
|
4
|
Sannathimmappa MB, Zehri L, Al Zadjali AAM, Albalushi HMA, Al Saadi BAAH, Aravindakshan R, Al-Risi ES, Al-Maqbali S, Nambiar V. Risk factors and outcome of hepatitis C infection among patients in a secondary care hospital: A 5-year retrospective study. JOURNAL OF EDUCATION AND HEALTH PROMOTION 2024; 13:208. [PMID: 39297119 PMCID: PMC11410161 DOI: 10.4103/jehp.jehp_1326_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 11/06/2023] [Indexed: 09/21/2024]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection, predominantly transmitted by exposure to infected blood, remains one of the major public health problems worldwide. This study aims to identify the risk factors of HCV transmission and its chronic complications among the study group. MATERIALS AND METHODS This retrospective study was approved by the Research and Ethical Review and Approve Committee (RERAC) of Oman and conducted at a secondary-care hospital situated in the North Batinah region of Oman. The study population included all HCV cases confirmed by positive serology and reverse-transcription polymerase chain reaction tests during their presence at the hospital between January 2017 and December 2022. The relevant data of the study population were retrieved from the hospital electronic health record system. The data were analyzed using the Statistical Package for the Social Sciences (SPSS), Version 26.0. RESULTS A total of 177 HCV confirmed cases were included in the study. HCV infection was predominant among males (74%) and individuals of the age group of 21-60 years (74.6%). Genotyping was possible only in 107 cases. Among HCV genotypes, genotype 3 (58.9%) was the most frequently identified, followed by genotype 1 (34.6%). Hemodialysis (21.5%), history of blood transfusion (16.4%), and injection drug use (11.9%) were the major risk factors for HCV infection, while cirrhosis (7.3%) and fatty liver disease (4%) were the most frequently observed chronic HCV complications. HCV infection in the spouse/partner (21.5%), alcohol use (7.3%), and co-infection with hepatitis B virus (2.3%) and human immunodeficiency virus (1.7%) were the other significant factors detected in our study population. CONCLUSIONS HCV is a multi-factorial disease leading to severe chronic complications, thus representing a public health threat. This clearly emphasizes the cruciality of HCV community awareness campaigns and enhancement of Omani national guidelines for early screening of high-risk groups as well as effective management of HCV-infected cases to reduce the substantial burden of the disease on patients as well as the healthcare system.
Collapse
Affiliation(s)
- Mohan B Sannathimmappa
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, National University of Science and Technology, Sohar Campus, Sultanate of Oman
| | - Latifa Zehri
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, National University of Science and Technology, Sohar Campus, Sultanate of Oman
| | - Ayat A M Al Zadjali
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, National University of Science and Technology, Sohar Campus, Sultanate of Oman
| | - Halima M A Albalushi
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, National University of Science and Technology, Sohar Campus, Sultanate of Oman
| | - Buthaina A A H Al Saadi
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, National University of Science and Technology, Sohar Campus, Sultanate of Oman
| | - Rajeev Aravindakshan
- Department of Community Medicine, All India Institute of Medical Sciences, Mangalagiri, Andhra Pradesh, India
| | - Elham S Al-Risi
- Department of Pathology and Blood Bank, Sohar Hospital, Oman
| | | | - Vinod Nambiar
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, National University of Science and Technology, Sohar Campus, Sultanate of Oman
| |
Collapse
|
|
5
|
Alshiban NM, Aleyiydi MS, Nassar MS, Alhumaid NK, Almangour TA, Tawfik YM, Damiati LA, Almutairi AS, Tawfik EA. Epidemiologic and clinical updates on viral infections in Saudi Arabia. Saudi Pharm J 2024; 32:102126. [PMID: 38966679 PMCID: PMC11223122 DOI: 10.1016/j.jsps.2024.102126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/06/2024] Open
Abstract
In the past two decades, the world has witnessed devastating pandemics affecting the global healthcare infrastructure and disrupting society and the economy worldwide. Among all pathogens, viruses play a critical role that is associated with outbreaks due to their wide range of species, involvement of animal hosts, easily transmitted to humans, and increased rates of infectivity. Viral disease outbreaks threaten public health globally due to the challenges associated with controlling and eradicating them. Implementing effective viral disease control programs starts with ongoing surveillance data collection and analyses to detect infectious disease trends and patterns, which is critical for maintaining public health. Viral disease control strategies include improved hygiene and sanitation facilities, eliminating arthropod vectors, vaccinations, and quarantine. The Saudi Ministry of Health (MOH) and the Public Health Authority (also known as Weqayah) in Saudi Arabia are responsible for public health surveillance to control and prevent infectious diseases. The notifiable viral diseases based on the Saudi MOH include hepatitis diseases, viral hemorrhagic fevers, respiratory viral diseases, exanthematous viral diseases, neurological viral diseases, and conjunctivitis. Monitoring trends and detecting changes in these viral diseases is essential to provide proper interventions, evaluate the established prevention programs, and develop better prevention strategies. Therefore, this review aims to highlight the epidemiological updates of the recently reported viral infections in Saudi Arabia and to provide insights into the recent clinical treatment and prevention strategies.
Collapse
Affiliation(s)
- Noura M. Alshiban
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| | - Munirah S. Aleyiydi
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| | - Majed S. Nassar
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| | - Nada K. Alhumaid
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| | - Thamer A. Almangour
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Yahya M.K. Tawfik
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Laila A. Damiati
- Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 23218, Saudi Arabia
| | | | - Essam A. Tawfik
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| |
Collapse
|
|
6
|
Jonas MM, Romero R, Rosenthal P, Lin CH, Verucchi G, Wen J, Balistreri WF, Whitworth S, Bansal S, Leung DH, Narkewicz MR, Gonzalez-Peralta RP, Mangia A, Karnsakul W, Rao GS, Shao J, de Jong J, Parhy B, Osinusi A, Kersey K, Murray KF, Sokal EM, Schwarz KB. Sofosbuvir-velpatasvir in children 3-17 years old with hepatitis C virus infection. J Pediatr Gastroenterol Nutr 2024; 78:1342-1354. [PMID: 38644678 DOI: 10.1002/jpn3.12045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 02/20/2023] [Accepted: 03/13/2023] [Indexed: 04/23/2024]
Abstract
BACKGROUND The safety and efficacy of sofosbuvir-velpatasvir in children aged 3-17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. METHODS In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir-velpatasvir 400/100 mg tablet (12-17 years), 200/50 mg low dose tablet or oral granules (3-11 years and ≥17 kg), or 150/37.5 mg oral granules (3-5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group. FINDINGS Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3-5-year-olds, 93% (68/73) among 6-11-year-olds, and 95% (97/102) among 12-17-year-olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12-17-year-olds; vomiting, cough, and headache in 6-11-year-olds; and vomiting in 3-5-year-olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS-331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight-based dosing for children in this age range. INTERPRETATION The pangenotypic regimen of sofosbuvir-velpatasvir is highly effective and safe in treating children 3-17 years with chronic HCV infection.
Collapse
Affiliation(s)
| | - Rene Romero
- Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, USA
| | - Philip Rosenthal
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of California San Francisco, Benioff Children's Hospital, San Francisco, California, USA
| | - Chuan-Hao Lin
- Children's Hospital Los Angeles, Los Angeles, California, USA
| | | | - Jessica Wen
- University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | | | | | | | - Daniel H Leung
- Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Michael R Narkewicz
- School of Medicine and Children's Hospital of Colorado, University of Colorado, Aurora, Colorado, USA
| | | | - Alessandra Mangia
- Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Wikrom Karnsakul
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Girish S Rao
- Riley Hospital for Children, Indiana University School of Medicine, Indiana, Indianapolis, USA
| | - Jiang Shao
- Gilead Sciences Inc., Foster City, California, USA
| | - Jan de Jong
- Gilead Sciences Inc., Foster City, California, USA
| | | | - Anu Osinusi
- Gilead Sciences Inc., Foster City, California, USA
| | | | - Karen F Murray
- Cleveland Clinic Children's Hospital, Cleveland, Ohio, USA
| | - Etienne M Sokal
- Cliniques Universitaires Saint-Luc, Service de Gastroentérologie Hépatologie Pédiatrique, Université Catholique de Louvain, Bruxelles, Belgique
| | | |
Collapse
|
|
7
|
Marković V, Szczepańska A, Berlicki Ł. Antiviral Protein-Protein Interaction Inhibitors. J Med Chem 2024; 67:3205-3231. [PMID: 38394369 PMCID: PMC10945500 DOI: 10.1021/acs.jmedchem.3c01543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 01/04/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024]
Abstract
Continually repeating outbreaks of pathogenic viruses necessitate the construction of effective antiviral strategies. Therefore, the development of new specific antiviral drugs in a well-established and efficient manner is crucial. Taking into account the strong ability of viruses to change, therapies with diversified molecular targets must be sought. In addition to the widely explored viral enzyme inhibitor approach, inhibition of protein-protein interactions is a very valuable strategy. In this Perspective, protein-protein interaction inhibitors targeting HIV, SARS-CoV-2, HCV, Ebola, Dengue, and Chikungunya viruses are reviewed and discussed. Antibodies, peptides/peptidomimetics, and small molecules constitute three classes of compounds that have been explored, and each of them has some advantages and disadvantages for drug development.
Collapse
Affiliation(s)
- Violeta Marković
- Wrocław
University of Science and Technology, Department
of Bioorganic Chemistry, Wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland
- University
of Kragujevac, Faculty of Science,
Department of Chemistry, R. Domanovića 12, 34000 Kragujevac, Serbia
| | - Anna Szczepańska
- Wrocław
University of Science and Technology, Department
of Bioorganic Chemistry, Wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland
| | - Łukasz Berlicki
- Wrocław
University of Science and Technology, Department
of Bioorganic Chemistry, Wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland
| |
Collapse
|
|
8
|
Wang W, Li K, Xiao W. The pharmacological role of Ginsenoside Rg3 in liver diseases: A review on molecular mechanisms. J Ginseng Res 2024; 48:129-139. [PMID: 38465219 PMCID: PMC10920009 DOI: 10.1016/j.jgr.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/23/2023] [Accepted: 11/10/2023] [Indexed: 03/12/2024] Open
Abstract
Liver diseases are a significant global health burden and are among the most common diseases. Ginssennoside Rg3 (Rg3), which is one of the most abundant ginsenosides, has been found to have significant preventive and therapeutic effects against various types of diseases with minimal side effects. Numerous studies have demonstrated the significant preventive and therapeutic effects of Rg3 on various liver diseases such as viral hepatitis, acute liver injury, nonalcoholic liver diseases (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). The underlying molecular mechanism behind these effects is attributed to apoptosis, autophagy, antioxidant, anti-inflammatory activities, and the regulation of multiple signaling pathways. This review provides a comprehensive description of the potential molecular mechanisms of Rg3 in the development of liver diseases. The article focuses on the regulation of apoptosis, oxidative stress, autophagy, inflammation, and other related factors. Additionally, the review discusses combination therapy and liver targeting strategy, which can accelerate the translation of Rg3 from bench to bedside. Overall, this article serves as a valuable reference for researchers and clinicians alike.
Collapse
Affiliation(s)
- Wenhong Wang
- Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, China
- The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China
| | - Ke Li
- Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, China
- The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China
| | - Weihua Xiao
- Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, China
- The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China
| |
Collapse
|
|
9
|
Martino SD, Petri GL, De Rosa M. Hepatitis C: The Story of a Long Journey through First, Second, and Third Generation NS3/4A Peptidomimetic Inhibitors. What Did We Learn? J Med Chem 2024; 67:885-921. [PMID: 38179950 DOI: 10.1021/acs.jmedchem.3c01971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2024]
Abstract
Hepatitis C viral (HCV) infection is the leading cause of liver failure and still represents a global health burden. Over the past decade, great advancements made HCV curable, and sustained viral remission significantly improved to more than 98%. Historical treatment with pegylated interferon alpha and ribavirin has been displaced by combinations of direct-acting antivirals. These regimens include drugs targeting different stages of the HCV life cycle. However, the emergence of viral resistance remains a big concern. The design of peptidomimetic inhibitors (PIs) able to fit and fill the conserved substrate envelope region within the active site helped avoid contact with the vulnerable sites of the most common resistance-associated substitutions Arg155, Ala156, and Asp168. Herein, we give an overview of HCV NS3 PIs discovered during the past decade, and we deeply discuss the rationale behind the structural optimization efforts essential to achieve pangenotypic activity.
Collapse
Affiliation(s)
- Simona Di Martino
- Drug Discovery Unit, Medicinal Chemistry Group, Ri.MED Foundation, Palermo 90133, Italy
| | - Giovanna Li Petri
- Drug Discovery Unit, Medicinal Chemistry Group, Ri.MED Foundation, Palermo 90133, Italy
| | - Maria De Rosa
- Drug Discovery Unit, Medicinal Chemistry Group, Ri.MED Foundation, Palermo 90133, Italy
| |
Collapse
|
|
10
|
Vincenzi M, Mercurio FA, Leone M. EPHA2 Receptor as a Possible Therapeutic Target in Viral Infections. Curr Med Chem 2024; 31:5670-5701. [PMID: 37828671 DOI: 10.2174/0109298673256638231003111234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 08/02/2023] [Accepted: 08/24/2023] [Indexed: 10/14/2023]
Abstract
BACKGROUND The receptor tyrosine kinase EphA2 plays a role in many diseases, like cancer, cataracts, and osteoporosis. Interestingly, it has also been linked to viral infections. OBJECTIVE Herein, current literature has been reviewed to clarify EphA2 functions in viral infections and explore its potential role as a target in antiviral drug discovery strategies. METHODS Research and review articles along with preprints connecting EphA2 to different viruses have been searched through PubMed and the web. Structures of complexes between EphA2 domains and viral proteins have been retrieved from the PDB database. RESULTS EphA2 assumes a key role in Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein Barr virus (EBV) infections by directly binding, through its ligand binding domain, viral glycoproteins. For human cytomegalovirus (HCMV), the role of EphA2 in maintaining virus latency state, through cooperation with specific viral proteins, has also been speculated. In certain cells, with high EphA2 expression levels, following ligand stimulation, receptor activation might contribute to severe symptoms accompanying a few viral infections, including lung injuries often related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). CONCLUSION Since EphA2 works as a host receptor for certain viruses, it might be worth more deeply investigating known compounds targeting its extracellular ligand binding domain as antiviral therapeutics. Due to EphA2's function in inflammation, its possible correlation with SARS-CoV-2 cannot be excluded, but more experimental studies are needed in this case to undoubtedly attribute the role of this receptor in viral infections.
Collapse
Affiliation(s)
- Marian Vincenzi
- Institute of Biostructures and Bioimaging, National Research Council of Italy (CNR-IBB), Naples, Italy
| | - Flavia Anna Mercurio
- Institute of Biostructures and Bioimaging, National Research Council of Italy (CNR-IBB), Naples, Italy
| | - Marilisa Leone
- Institute of Biostructures and Bioimaging, National Research Council of Italy (CNR-IBB), Naples, Italy
| |
Collapse
|
|
11
|
Liu Y, Su J, Wang X, Xu H, Wang H, Kang R, Zheng L, Wang Y, Liu C, Jing Y, Zhang S. Hepatitis C Knowledge and Self-Reported Testing Behavior in the General Population in China: Online Cross-Sectional Survey. JMIR Public Health Surveill 2023; 9:e39472. [PMID: 38079213 PMCID: PMC10760629 DOI: 10.2196/39472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 08/08/2023] [Accepted: 11/09/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND The World Health Organization has proposed a worldwide target of eliminating hepatitis C virus (HCV) by 2030. A better understanding of HCV, testing behaviors, and associated factors in the general population is essential. OBJECTIVE This study aimed to assess HCV knowledge, self-reported HCV testing behavior, and willingness to undergo HCV screening in the general Chinese population. METHODS A cross-sectional online survey of the general Chinese population aged ≥15 years was conducted from November 2021 to May 2023. Participant characteristics were assessed based on their knowledge level and uptake of HCV testing. Participants ever having heard of HCV were recognized as being aware of HCV and asked additional HCV knowledge questions using a brief, validated 9-item scale. Participants with 0-3 points and who were unaware of HCV were categorized as having poor knowledge, and those with 4-6 points and 7 points were categorized as having fair and good knowledge, respectively. Participant uptake of HCV testing, testing results, reasons for undergoing or not undergoing HCV testing, and willingness to undergo HCV screening were collected through self-reports. Ordinal and binary logistic regression analyses were used to assess factors associated with the HCV knowledge level and the uptake of HCV testing, respectively. RESULTS A total of 1491 valid participants' questionnaires were included. Of these, 714 (47.6%) participants were aware of HCV. The proportion of participants with poor, fair, and good HCV knowledge was 63.4% (945/1491), 9.3% (139/1491), and 27.3% (407/1491), respectively. A total of 465 (31.2%) participants reported ever undergoing HCV testing, and 4 (0.9%) were anti-HCV antibody positive. Most participants were tested for HCV following blood donation (353/465, 75.9%). The most common reasons for not undergoing HCV screening were a lack of HCV awareness (665/1026, 64.8%), followed by a low self-perceived risk of infection (176/1026, 17.2%). Of 1026 participants who had never undergone HCV testing, 937 (91.3%) were willing to undergo HCV screening if universal screening was provided at no cost. The HCV knowledge level was positively associated with the HCV testing rate. Participants who were less educated, lived in rural areas, resided in West China, and were currently alcohol drinkers had lower HCV knowledge and reduced odds of having undergone HCV testing. In contrast, participants with a blood donation history and a family history of hepatitis B virus or HCV infection had higher HCV knowledge and increased odds of prior testing. Participants aged ≥60 years had lower knowledge, and women had reduced odds of having undergone previous HCV testing. CONCLUSIONS The general population of China has low HCV knowledge and testing rate. There is an urgent need for enhanced HCV awareness and scaled-up HCV screening and treatment. Individuals who are less well educated, reside in less-developed areas, currently drink alcohol, and are female should be prioritized for health education and interventions.
Collapse
Affiliation(s)
- Yin Liu
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Juan Su
- Yinchuan Hospital of Stomatology, Yinchuan, China
| | - Xiaoyang Wang
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Huifang Xu
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Hong Wang
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Ruihua Kang
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Liyang Zheng
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Yixian Wang
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Chunya Liu
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Yiping Jing
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Shaokai Zhang
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| |
Collapse
|
|
12
|
Pugliese N, Polverini D, Arcari I, De Nicola S, Colapietro F, Masetti C, Ormas M, Ceriani R, Lleo A, Aghemo A. Hepatitis C Virus Infection in the Elderly in the Era of Direct-Acting Antivirals: Evidence from Clinical Trials and Real Life. Trop Med Infect Dis 2023; 8:502. [PMID: 37999621 PMCID: PMC10674442 DOI: 10.3390/tropicalmed8110502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/09/2023] [Accepted: 11/16/2023] [Indexed: 11/25/2023] Open
Abstract
The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug-drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.
Collapse
Affiliation(s)
- Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Davide Polverini
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Ivan Arcari
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Stella De Nicola
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Chiara Masetti
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Monica Ormas
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Roberto Ceriani
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| |
Collapse
|
|
13
|
Prabhu SS, Nair AS, Nirmala SV. Multifaceted roles of mitochondrial dysfunction in diseases: from powerhouses to saboteurs. Arch Pharm Res 2023; 46:723-743. [PMID: 37751031 DOI: 10.1007/s12272-023-01465-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 09/19/2023] [Indexed: 09/27/2023]
Abstract
The fact that mitochondria play a crucial part in energy generation has led to the nickname "powerhouses" of the cell being applied to them. They also play a significant role in many other cellular functions, including calcium signalling, apoptosis, and the creation of vital biomolecules. As a result, cellular function and health as a whole can be significantly impacted by mitochondrial malfunction. Indeed, malignancies frequently have increased levels of mitochondrial biogenesis and quality control. Adverse selection exists for harmful mitochondrial genome mutations, even though certain malignancies include modifications in the nuclear-encoded tricarboxylic acid cycle enzymes that generate carcinogenic metabolites. Since rare human cancers with mutated mitochondrial genomes are often benign, removing mitochondrial DNA reduces carcinogenesis. Therefore, targeting mitochondria offers therapeutic options since they serve several functions and are crucial to developing malignant tumors. Here, we discuss the various steps involved in the mechanism of cancer for which mitochondria plays a significant role, as well as the role of mitochondria in diseases other than cancer. It is crucial to understand mitochondrial malfunction to target these organelles for therapeutic reasons. This highlights the significance of investigating mitochondrial dysfunction in cancer and other disease research.
Collapse
Affiliation(s)
- Surapriya Surendranath Prabhu
- Department of Pharmaceutical Chemistry and Analysis, Amrita School of Pharmacy, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India
| | - Aathira Sujathan Nair
- Department of Pharmaceutical Chemistry and Analysis, Amrita School of Pharmacy, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India
| | - Saiprabha Vijayakumar Nirmala
- Department of Pharmaceutical Chemistry and Analysis, Amrita School of Pharmacy, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India.
| |
Collapse
|
|
14
|
Hansoongnern P, Pratedrat P, Nilyanimit P, Wasitthankasem R, Posuwan N, Wanlapakorn N, Kodchakorn K, Kongtawelert P, Pimsing N, Poovorawan Y. An amino acid substitution in HCV core antigen limits its use as a reliable measure of HCV infection compared with HCV RNA. PLoS One 2023; 18:e0287694. [PMID: 37384719 PMCID: PMC10310030 DOI: 10.1371/journal.pone.0287694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 06/12/2023] [Indexed: 07/01/2023] Open
Abstract
Hepatitis C virus (HCV) is a viral pathogen that causes chronic hepatitis, which can lead to cirrhosis and hepatocellular carcinoma. Detection of HCV RNA is the standard method used to diagnose the disease and monitor antiviral treatment. A quantification assay for the HCV core antigen (HCVcAg) has been proposed as a simplified alternative to the HCV RNA test for predicting active HCV infection, with the aim of achieving the global goal of eliminating hepatitis. The objective of this study was to determine the correlation between HCV RNA and HCVcAg, as well as the impact of amino acid sequence heterogeneity on HCVcAg quantification. Our findings demonstrated a strong positive correlation between HCV RNA and HCVcAg across all HCV genotypes (1a, 1b, 3a, and 6), with correlation coefficients ranging from 0.88 to 0.96 (p < 0.001). However, in some cases, samples with genotypes 3a and 6 exhibited lower HCVcAg levels than expected based on the corresponding HCV RNA values. Upon the core amino acid sequence alignment, it was observed that samples exhibiting low core antigen levels had an amino acid substitution at position 49, where threonine was replaced by either alanine or valine. Core mutation at this position may correlate with one of the epitope regions recognized by anti-HCV monoclonal antibodies. The present findings suggest that the utilization of HCVcAg as a standalone marker for HCV RNA might not provide adequate sensitivity for the detection of HCV infection, especially in cases where there are variations in the amino acid sequence of the core region and a low viral load of HCV RNA.
Collapse
Affiliation(s)
- Payuda Hansoongnern
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pornpitra Pratedrat
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pornjarim Nilyanimit
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Rujipat Wasitthankasem
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- National Biobank of Thailand, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Nawarat Posuwan
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Nasamon Wanlapakorn
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Kanchanok Kodchakorn
- Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Prachya Kongtawelert
- Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Napaporn Pimsing
- Non-Communicable Disease Control Group, Phetchabun Provincial Health Office, Phetchabun, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Fellow of the Royal Society of Thailand (FRS[T]), the Royal Society of Thailand, Sanam Sueapa, Bangkok, Thailand
| |
Collapse
|
|
15
|
Du Y, Khera T, Liu Z, Tudrujek-Zdunek M, Dworzanska A, Cornberg M, Xu CJ, Tomasiewicz K, Wedemeyer H. Controlled Attenuation Parameter Is Associated with a Distinct Systemic Inflammatory Milieu after Clearance of HCV Infection. Biomedicines 2023; 11:1529. [PMID: 37371624 DOI: 10.3390/biomedicines11061529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 05/15/2023] [Accepted: 05/17/2023] [Indexed: 06/29/2023] Open
Abstract
Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects along with a high prevalence of hepatic steatosis. After HCV clearance, steatosis persists in many patients. However, the reasons behind this phenomenon are not completely clear. To investigate the association between 92 soluble inflammatory mediators (SIMs) and the steatosis grade, we made use of a cohort of 94 patients with chronic HCV infection who cleared HCV after direct-acting antiviral agent (DAA) treatment. Patients were classified into three groups according to their controlled attenuation parameter (CAP). CAP is associated with ALT, γ-GT and liver stiffness after HCV clearance. While stem cell factor (SCF) and tumor necrosis factor ligand superfamily member 12 (TWEAK) levels were significantly reduced in patients with CAP > 299 dB/m, the levels of fibroblast growth factor (FGF)-21 and interleukin-18 receptor 1 (IL-18R1) were higher in those patients at week 96 after virus clearance. These four markers also showed a linear correlation with CAP values. FGF-21 levels correlated with CAP only after HCV clearance. Taken together, these four biomarkers, namely SCF, TWEAK, FGF-21 and IL-18R1, are associated with CAP status after virus clearance. A potential role of these proteins in the pathogenesis of post-sustained viral response (SVR) nonalcoholic steatohepatitis requires further investigation.
Collapse
Affiliation(s)
- Yanqin Du
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Infectious Diseases, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Tanvi Khera
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- International AIDS Vaccine Initiative (IAVI), 122002 Gurugram, Haryana, India
| | - Zhaoli Liu
- Centre for Individualized Infection Medicine (CiiM), a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
| | | | - Anna Dworzanska
- Department of Infectious Diseases, Medical University of Lublin, 20-081 Lublin, Poland
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
| | - Cheng-Jian Xu
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- Centre for Individualized Infection Medicine (CiiM), a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-081 Lublin, Poland
| | - Heiner Wedemeyer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- Excellence Cluster Resist, Hannover Medical School, 30625 Hannover, Germany
| |
Collapse
|
|
16
|
Manzoor S, Malik IR, Jahan S, Sarwar MB, Bashir A, Shams S, Hussain A. Serum MicroRNAs as Predictors for HCV Progression and Response to Treatment in Pakistani Patients. Genes (Basel) 2023; 14:441. [PMID: 36833368 PMCID: PMC9957303 DOI: 10.3390/genes14020441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/14/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Hepatitis is one of the common liver diseases, imposing a heavy health burden worldwide. Acute hepatitis may develop into chronic hepatitis, progressing to cirrhosis and hepatocellular carcinoma. In the present study, the expression of miRNAs was quantified by real-time PCR, such as miRNA-182, 122, 21, 150, 199, and 222. Along with the control group, HCV was divided into chronic, cirrhosis, and HCC groups. The treated group was also included after the successful treatment of HCV. Biochemical parameters, such as ALT, AST, ALP, bilirubin, viral load, and AFP (HCC), were also evaluated in all of the study groups. We compared the control and diseased groups; these parameters showed significant results (p = 0.000). The viral load was high in HCV but was not detected after treatment. miRNA-182 and miRNA-21 were overexpressed with disease progression, while the expression of miRNA-122 and miRNA-199 was increased compared with the control, but decreased in the cirrhosis stage compared with chronic and HCC. The expression of miRNA-150 was increased in all of the diseased groups compared with the control, but decreased compared with the chronic group. We compared the chronic and treated groups and then all of these miRNAs were down-regulated after treatment. These microRNAs could be used as potential biomarkers for diagnosing different stages of HCV.
Collapse
Affiliation(s)
- Sadia Manzoor
- Department of Biotechnology, University of Sargodha, Sargodha 40100, Pakistan
| | - Imran Riaz Malik
- Department of Biotechnology, University of Sargodha, Sargodha 40100, Pakistan
| | - Shah Jahan
- Department of Immunology, University of Health Sciences, Lahore 54700, Pakistan
| | - Muhammad Bilal Sarwar
- Food and Biotechnology Research Center, PCSIR Laboratories Complex Lahore, Lahore 54700, Pakistan
| | - Asma Bashir
- Department of Biosciences, Faculty of Life Sciences, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology (SZABIST), Karachi 75600, Pakistan
| | - Sulaiman Shams
- Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
| | - Abrar Hussain
- Faculty of Life Sciences and Informatics, BUITEMS, Quetta 87300, Pakistan
| |
Collapse
|
|
17
|
Nasr T, Aboshanab AM, Mpekoulis G, Drakopoulos A, Vassilaki N, Zoidis G, Abouzid KAM, Zaghary W. Novel 6-Aminoquinazolinone Derivatives as Potential Cross GT1-4 HCV NS5B Inhibitors. Viruses 2022; 14:v14122767. [PMID: 36560772 PMCID: PMC9782603 DOI: 10.3390/v14122767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 12/04/2022] [Accepted: 12/07/2022] [Indexed: 12/15/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infections are a worldwide medical problem responsible for diverse types of liver diseases. The NS5B polymerase enzyme has become a very interesting target for the development of anti-HCV drugs owing to its fundamental role in viral replication. Here we report the synthesis of a novel series of 1-substituted phenyl-4(1H)-quinazolinone and 2-methyl-1-substituted phenyl-4(1H)-quinazolinone derivatives and evaluate their activity against HCV in HCV subgenomic replicon assays. The biological data revealed that compound 11a showed the highest activity against HCV GT1b at a micromolar concentration (EC50 = 0.984 µM) followed by compound 11b (EC50 = 1.38 µM). Both compounds 11a and 11b had high selectivity indices (SI = CC50/EC50), 160.71 and 71.75, respectively, which make them very interesting candidates for further development of more potent and selective anti-HCV agents.
Collapse
Affiliation(s)
- Tamer Nasr
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain-Helwan, Cairo 11795, Egypt
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, MTI University, Cairo 12055, Egypt
- Correspondence: (T.N.); (G.Z.)
| | - Ahmed M. Aboshanab
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain-Helwan, Cairo 11795, Egypt
| | - George Mpekoulis
- Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece
| | - Antonios Drakopoulos
- Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden
| | - Niki Vassilaki
- Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece
| | - Grigoris Zoidis
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
- Correspondence: (T.N.); (G.Z.)
| | - Khaled A. M. Abouzid
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt
| | - Wafaa Zaghary
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain-Helwan, Cairo 11795, Egypt
| |
Collapse
|
|
18
|
Antropova E, Khlebodarova T, Demenkov P, Venzel A, Ivanisenko N, Gavrilenko A, Ivanisenko T, Adamovskaya A, Revva P, Lavrik I, Ivanisenko V. Computer analysis of regulation of hepatocarcinoma marker genes hypermethylated by HCV proteins. Vavilovskii Zhurnal Genet Selektsii 2022; 26:733-742. [PMID: 36714033 PMCID: PMC9840909 DOI: 10.18699/vjgb-22-89] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 11/22/2022] [Accepted: 11/22/2022] [Indexed: 01/07/2023] Open
Abstract
Hepatitis C virus (HCV) is a risk factor that leads to hepatocellular carcinoma (HCC) development. Epigenetic changes are known to play an important role in the molecular genetic mechanisms of virus-induced oncogenesis. Aberrant DNA methylation is a mediator of epigenetic changes that are closely associated with the HCC pathogenesis and considered a biomarker for its early diagnosis. The ANDSystem software package was used to reconstruct and evaluate the statistical significance of the pathways HCV could potentially use to regulate 32 hypermethylated genes in HCC, including both oncosuppressor and protumorigenic ones identified by genome-wide analysis of DNA methylation. The reconstructed pathways included those affecting protein-protein interactions (PPI), gene expression, protein activity, stability, and transport regulations, the expression regulation pathways being statistically significant. It has been shown that 8 out of 10 HCV proteins were involved in these pathways, the HCV NS3 protein being implicated in the largest number of regulatory pathways. NS3 was associated with the regulation of 5 tumor-suppressor genes, which may be the evidence of its central role in HCC pathogenesis. Analysis of the reconstructed pathways has demonstrated that following the transcription factor inhibition caused by binding to viral proteins, the expression of a number of oncosuppressors (WT1, MGMT, SOCS1, P53) was suppressed, while the expression of others (RASF1, RUNX3, WIF1, DAPK1) was activated. Thus, the performed gene-network reconstruction has shown that HCV proteins can influence not only the methylation status of oncosuppressor genes, but also their transcriptional regulation. The results obtained can be used in the search for pharmacological targets to develop new drugs against HCV-induced HCC.
Collapse
Affiliation(s)
- E.A. Antropova
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Scences, Novosibirsk, Russia
| | - T.M. Khlebodarova
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Scences, Novosibirsk, RussiaKurchatov Genomic Center of ICG SB RAS, Novosibirsk, Russia
| | - P.S. Demenkov
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Scences, Novosibirsk, RussiaKurchatov Genomic Center of ICG SB RAS, Novosibirsk, Russia
| | - A.S. Venzel
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Scences, Novosibirsk, RussiaKurchatov Genomic Center of ICG SB RAS, Novosibirsk, Russia
| | - N.V. Ivanisenko
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Scences, Novosibirsk, RussiaKurchatov Genomic Center of ICG SB RAS, Novosibirsk, Russia
| | - A.D. Gavrilenko
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Scences, Novosibirsk, RussiaNovosibirsk State University, Novosibirsk, Russia
| | - T.V. Ivanisenko
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Scences, Novosibirsk, RussiaKurchatov Genomic Center of ICG SB RAS, Novosibirsk, Russia
| | - A.V. Adamovskaya
- Kurchatov Genomic Center of ICG SB RAS, Novosibirsk, RussiaNovosibirsk State University, Novosibirsk, Russia
| | - P.M. Revva
- Kurchatov Genomic Center of ICG SB RAS, Novosibirsk, RussiaKurchatov Genomic Center of ICG SB RAS, Novosibirsk, Russia
| | - I.N. Lavrik
- Translational Inflammation Research, Medical Faculty, Otto von Guericke University Magdeburg, Magdeburg, Germany
| | - V.A. Ivanisenko
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Scences, Novosibirsk, RussiaKurchatov Genomic Center of ICG SB RAS, Novosibirsk, RussiaNovosibirsk State University, Novosibirsk, Russia
| |
Collapse
|
|
19
|
Kashnikova AD, Bystrova TN, Polyanina AV, Zalesskikh, AA. Genetic Monitoring as a Component of Hepatitis C Surveillance. ЗДОРОВЬЕ НАСЕЛЕНИЯ И СРЕДА ОБИТАНИЯ - ЗНИСО / PUBLIC HEALTH AND LIFE ENVIRONMENT 2022:76-81. [DOI: 10.35627/2219-5238/2022-30-11-76-81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Background: The hepatitis C virus is known for its high spontaneous mutation rate and genetic heterogeneity. Genotype distribution varies greatly between different regions of Russia. This phenomenon reflects autonomous nature of the epidemic process of the hepatitis C infection.
Objective: To investigate and analyze the diversity of genetic variants of the hepatitis C virus currently circulating in the city of Nizhny Novgorod.
Material and methods: Official hepatitis C incidence data for the Nizhny Novgorod Region were analyzed retrospectively. From the blood serum bank, we obtained 142,254 serum samples from examined outpatients and patients admitted to hospitals for noninfectious diseases. Laboratory testing included detection of the following markers for hepatitis C virus infection: serum anti-HCV IgM and IgG, antibodies to structural and non-structural viral proteins. A part of seropositive samples was tested for HCV RNA and genotyped by real-time PCR.
Results: We observed stabilization of the trend in the incidence of acute hepatitis C in Nizhny Novgorod and a steady decrease in the incidence of newly diagnosed chronic hepatitis C. The antibody serology tests showed that the prevalence of anti-HCV was 3.1 ± 0.1 per 100 examined persons. HCV RNA was detected in 1.9 ± 0.1 % of adults, the most affected being those aged 40–49 years. Subtypes 1b and 3a prevailed while subtype 1a, genotype 2, and mixed variants were rare.
Conclusion: Introduction of advances in genetic diagnosis into the system of epidemiologic hepatitis C surveillance is determined by the relevance of conducting a comprehensive examination of people infected with HCV in order to monitor circulation of hepatitis C virus genotypes/subtypes and to understand the evolution and epidemiological features of the disease in different areas.
Collapse
|
|
20
|
Xiang Z, Li J, Lu D, Wei X, Xu X. Advances in multi-omics research on viral hepatitis. Front Microbiol 2022; 13:987324. [PMID: 36118247 PMCID: PMC9478034 DOI: 10.3389/fmicb.2022.987324] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 08/11/2022] [Indexed: 11/13/2022] Open
Abstract
Viral hepatitis is a major global public health problem that affects hundreds of millions of people and is associated with significant morbidity and mortality. Five biologically unrelated hepatotropic viruses account for the majority of the global burden of viral hepatitis, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Omics is defined as the comprehensive study of the functions, relationships and roles of various types of molecules in biological cells. The multi-omics analysis has been proposed and considered key to advancing clinical precision medicine, mainly including genomics, transcriptomics and proteomics, metabolomics. Overall, the applications of multi-omics can show the origin of hepatitis viruses, explore the diagnostic and prognostics biomarkers and screen out the therapeutic targets for viral hepatitis and related diseases. To better understand the pathogenesis of viral hepatitis and related diseases, comprehensive multi-omics analysis has been widely carried out. This review mainly summarizes the applications of multi-omics in different types of viral hepatitis and related diseases, aiming to provide new insight into these diseases.
Collapse
Affiliation(s)
- Ze Xiang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiayuan Li
- Zhejiang University School of Medicine, Hangzhou, China
| | - Di Lu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
| | - Xuyong Wei
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- Xuyong Wei,
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- *Correspondence: Xiao Xu,
| |
Collapse
|
|
21
|
Kham-Kjing N, Ngo-Giang-Huong N, Tragoolpua K, Khamduang W, Hongjaisee S. Highly Specific and Rapid Detection of Hepatitis C Virus Using RT-LAMP-Coupled CRISPR-Cas12 Assay. Diagnostics (Basel) 2022; 12:diagnostics12071524. [PMID: 35885430 PMCID: PMC9317538 DOI: 10.3390/diagnostics12071524] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/17/2022] [Accepted: 06/17/2022] [Indexed: 12/23/2022] Open
Abstract
Hepatitis C virus (HCV) infection can be cured with pan-genotypic direct-acting antiviral agents. However, identifying individuals with current hepatitis C remains a major challenge, especially in resource-limited settings where access to or availability of molecular tests is still limited. The goal of this study was to develop and validate a molecular assay for the rapid detection of HCV RNA in resource-limited settings. It is based on a combination of reverse transcription loop-mediated isothermal amplification (RT-LAMP) with the clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 12a (CRISPR–Cas12a) cleavage assay that allows the recognition of specific HCV nucleic acid sequences. Amplified products after the cleavage reactions can be visualized on lateral flow strips or measured with a fluorescence detector. When tested on clinical samples from individuals infected with HCV, HIV, or HBV, or from healthy donors, the RT-LAMP-coupled CRISPR–Cas12 assay yielded 96% sensitivity, 100% specificity, and 97% agreement as compared to the reference method (Roche COBAS AmpliPrep/COBAS TaqMan HCV Test). This assay could detect HCV RNA concentrations as low as 10 ng/µL (an estimated 2.38 Log10 IU/mL). Therefore, this sensitive and specific assay may represent an affordable and reliable point-of-care test for the identification of individuals with active hepatitis C in low-resource settings.
Collapse
Affiliation(s)
- Nang Kham-Kjing
- Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.-K.); (K.T.)
| | - Nicole Ngo-Giang-Huong
- Maladies Infectieuses et Vecteurs: Écologie, Génétique, Évolution et Contrôle (MIVEGEC), Agropolis University Montpellier, Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pour le Développement (IRD), 34394 Montpellier, France;
- Associated Medical Sciences (AMS)-PHPT Research Collaboration, Chiang Mai 50200, Thailand
| | - Khajornsak Tragoolpua
- Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.-K.); (K.T.)
- Infectious Diseases Research Unit, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Woottichai Khamduang
- Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.-K.); (K.T.)
- Associated Medical Sciences (AMS)-PHPT Research Collaboration, Chiang Mai 50200, Thailand
- Infectious Diseases Research Unit, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
- Correspondence: (W.K.); (S.H.)
| | - Sayamon Hongjaisee
- Research Institute for Health Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
- Correspondence: (W.K.); (S.H.)
| |
Collapse
|
|
22
|
Badami E, Busà R, Douradinha B, Russelli G, Miceli V, Gallo A, Zito G, Conaldi PG, Iannolo G. Hepatocellular carcinoma, hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches. World J Gastroenterol 2022; 28:2417-2428. [PMID: 35979260 PMCID: PMC9258280 DOI: 10.3748/wjg.v28.i22.2417] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/22/2022] [Accepted: 04/15/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is the principal etiology of cirrhosis and, ultimately, hepatocellular carcinoma (HCC). At present, approximately 71 million people are chronically infected with HCV, and 10%–20% of these are expected to develop severe liver complications throughout their lifetime. Scientific evidence has clearly shown the causal association between miRNAs, HCV infection and HCC. Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development, variations in miRNA patterns have been described in different liver diseases, including HCC. Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis. In this Review, we aim to summarize current knowledge on the association between miRNA, HCV and HCC from a diagnostic point of view, and also the potential implications for therapeutic approaches.
Collapse
Affiliation(s)
- Ester Badami
- Regenerative Medicine and Immunotherapy Area, Fondazione Ri.MED, Palermo 90127, Italy
| | - Rosalia Busà
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Bruno Douradinha
- Regenerative Medicine and Immunotherapy Area, Fondazione Ri.MED, Palermo 90127, Italy
| | - Giovanna Russelli
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Vitale Miceli
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Alessia Gallo
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Giovanni Zito
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Pier Giulio Conaldi
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Gioacchin Iannolo
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| |
Collapse
|
|
23
|
Binding of GS-461203 and Its Halogen Derivatives to HCV Genotype 2a RNA Polymerase Drug Resistance Mutants. Sci Pharm 2022. [DOI: 10.3390/scipharm90020026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Hepatitis C Virus (HCV) is reported to develop GS-461203 resistance because of multiple mutations within the RNA-dependent RNA Polymerase (RdRp) of HCV. The lack of a high-resolution structure of these RdRp mutants in complex with GS-461203 hinders efforts to understand the drug resistance. Here we decipher the binding differences of GS-461203 in the wild type and mutated systems T179A or M289L of HCV RdRp Genotype 2a using homology modeling, molecular docking, and molecular dynamics simulation. Key residues responsible for GS-461203 binding were identified to be Arg48, Arg158, Asp318, Asp319, and Asp220, and that mutations T179A or M289L have caused conformational changes of GS-461203 in the RdRp active site. The affinities of GS-461203 were reduced in T179A system, but it became slightly stronger in the M289L system. Furthermore, we designed two new analogues of GS-461203 which encouragingly induced more stable interactions than GS-461203, and thus resulted in much better binding energies. This present study reveals how a single mutation, T179A or M289L, will modulate GS-461203 binding in HCV RdRp Genotype 2a, while introducing two novel analogues to overcome the drug resistance which may be good candidate for further experimental verification.
Collapse
|
|
24
|
Reexamining Povarov Reaction’s Scope and Limitation in the Generation of HCV-NS4A Peptidomimetics. HETEROATOM CHEMISTRY 2022. [DOI: 10.1155/2022/8181543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Chronic Hepatitis C is a global health threat and a silent killer. Regardless of the profound progress in preventing and treating this disease, research continues to discover new direct antiviral agents (DAAs), especially against novel targets. Our research has been directed to leverage the NS4A binding site to develop peptidomimetic inhibitors of the hepatitis C virus (HCV) NS3 protease. In previous reports, we could provide evidence of tunability of this site by peptide and nonpeptide NS3/4A inhibitors. In this report, we used structure-based techniques to design 1,2,3,4-tetrahydro-1,7-naphthyridine derivative as NS4A core mimics that cover the region between residues Ile-25′ to Arg-28′. The synthetic plan featured the Povarov reaction as an efficient strategy to construct the 1,7-naphthyridine core. Although this reaction has been reported in many literatures, critical assessments for its scope and limitations are scarce. In our work, we found that Povarov was extremely sensitive to alkene and aldehyde reactants. Moreover, using pyridine amines was not as successful as anilines. The most striking results were the lack of stability of compounds during purification and storage. The four compounds that survived the stability problems (1a-1d) did not show significant binding potency with NS3, because their structures were too simple to resemble the originally planned compounds.
Collapse
|
|
25
|
Sinopoli A, Isonne C, Santoro MM, Baccolini V. The effects of orally administered lactoferrin in the prevention and management of viral infections: A systematic review. Rev Med Virol 2022; 32:e2261. [PMID: 34133812 PMCID: PMC9286571 DOI: 10.1002/rmv.2261] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 05/18/2021] [Indexed: 12/24/2022]
Abstract
It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk-Of-Bias and ROBINS-1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better-designed studies are needed to further investigate its potential benefits against viral infections, including SARS-CoV-2.
Collapse
Affiliation(s)
- Alessandra Sinopoli
- Department of PreventionLocal Health Unit Roma 1RomeItaly
- Department of Experimental MedicineUniversity of Rome “Tor Vergata”RomeItaly
| | - Claudia Isonne
- Department of Public Health and Infectious DiseasesSapienza University of RomeRomeItaly
| | | | - Valentina Baccolini
- Department of Public Health and Infectious DiseasesSapienza University of RomeRomeItaly
| |
Collapse
|
|
26
|
Bernier C, Goetz C, Jubinville E, Jean J. The New Face of Berries: A Review of Their Antiviral Proprieties. Foods 2021; 11:102. [PMID: 35010229 PMCID: PMC8750760 DOI: 10.3390/foods11010102] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/21/2021] [Accepted: 12/24/2021] [Indexed: 12/28/2022] Open
Abstract
Due to rising consumer preference for natural remedies, the search for natural antiviral agents has accelerated considerably in recent years. Among the natural sources of compounds with potential antiviral proprieties, berries are interesting candidates, due to their association with health-promoting properties, including antioxidant, antimutagenic, anticancer, antimicrobial, anti-inflammatory, and neuroprotective properties. The past two decades have witnessed a flurry of new findings. Studies suggest promising antiviral proprieties against enveloped and non-enveloped viruses, particularly of cranberries, blueberries, blackcurrants, black raspberries, and pomegranates. The aim of this review is to assemble these findings, to list the implied mechanisms of action, and thereby point out promising subjects for research in this field, in the hope that compounds obtainable from natural sources such as berries may be used someday to treat, or even prevent, viral infections.
Collapse
Affiliation(s)
| | | | | | - Julie Jean
- Department of Food Sciences, Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec, QC G1V 0A6, Canada; (C.B.); (C.G.); (E.J.)
| |
Collapse
|
|
27
|
Abstract
Hepatitis C in children is on the rise due to perinatal transmission from infected mothers, and high-risk practices in adolescents and young adults. Prevalence remains underestimated because children at high risk are often not screened. Treatment has evolved over the past decade with the advent of new drugs, and global elimination is now possible. Direct-acting antiviral combinations are safe and effective, with sustained viral suppression rate >90%, and Food and Drug Administration-approved for children ≥3 years old. Although challenging, efficient screening and treatment of chronic hepatitis C virus early is cost-effective and reduces burden of disease and its complications.
Collapse
Affiliation(s)
- Sanu R Yadav
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Children's Hospital, 8950 Euclid Avenue, R3, Cleveland, OH 44195, USA
| | - Deborah A Goldman
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Children's Hospital, 8950 Euclid Avenue, R3, Cleveland, OH 44195, USA
| | - Karen F Murray
- Cleveland Clinic Children's Hospital, 8950 Euclid Avenue, R3, Cleveland, OH 44195, USA.
| |
Collapse
|
|
28
|
Two New Purification Methods of Hepatitis C Virus Particles from Serum-Free Culture System. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.115727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: The traditional ultracentrifugation purification method of hepatitis C virus (HCV) particles requires special equipment, limiting its wide application. Therefore, more effective and convenient methods for HCV are needed. Objectives: The present study aimed to establish simple and effective purification methods for HCV. Methods: The infectious clone of the HCV genome (JFH-1) was transfected to the human hepatoma cell line (Huh7.5.1) and cultured in Dulbecco’s modified eagle medium/nutrient mixture F-12. The infectivity of JFH-1 culture was determined by reverse transcription-quantitative polymerase chain reaction and immunofluorescence. After concentration by centrifugal filter devices, HCV particles were purified by heparin-affinity chromatography and magnetic separation technique. The purified viruses were detected by the western blot and immune-electron microscopy. Results: The infectious titer of JFH-1 transfected Huh7.5.1 in the serum-free culture medium was 4.5 × 104 FFU/mL, and HCV ribonucleic acid load was 3.946 × 106 IU/mL in 30 days of cell culture post-transfection. After purification by heparin-affinity chromatography or magnetic separation method, viral particles were visualized with spherical morphology and an average diameter of 55 nm assessed by electron microscopy. The viruses were confirmed by the western blot and immune-electron microscopy with specific antibodies to HCV. Conclusions: The heparin-affinity chromatography and magnetic separation methods were established for the purification of HCV, which were simple and efficient methods for the stable purification of HCV particles on a large scale.
Collapse
|
|
29
|
Mirzaie S, Abdi F, GhavamiNejad A, Lu B, Wu XY. Covalent Antiviral Agents. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1322:285-312. [PMID: 34258745 DOI: 10.1007/978-981-16-0267-2_11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Nowadays, many viral infections have emerged and are taking a huge toll on human lives globally. Meanwhile, viral resistance to current drugs has drastically increased. Hence, there is a pressing need to design potent broad-spectrum antiviral agents to treat a variety of viral infections and overcome viral resistance. Covalent inhibitors have the potential to achieve both goals owing to their biochemical efficiency, prolonged duration of action, and the capability to inhibit shallow, solvent-exposed substrate-binding domains. In this chapter, we review the structures, activities, and inhibition mechanisms of covalent inhibitors against severe acute respiratory syndrome coronavirus 2, dengue virus, enterovirus, hepatitis C virus, human immunodeficiency virus, and influenza viruses. We also discuss the application of in silico study in covalent inhibitor design.
Collapse
Affiliation(s)
- Sako Mirzaie
- Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
| | - Fatemeh Abdi
- Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
| | - Amin GhavamiNejad
- Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
| | - Brian Lu
- Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
| | - Xiao Yu Wu
- Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
| |
Collapse
|
|
30
|
Matsumoto T, Tsuchiya T, Hirano T, Laurent T, Matsunaga K, Takata J. Changes in the Penetration Rate of Biosimilar Infliximab Within Japan Using a Japanese Claims Database. CLINICOECONOMICS AND OUTCOMES RESEARCH 2021; 13:145-153. [PMID: 33658813 PMCID: PMC7920501 DOI: 10.2147/ceor.s293698] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 02/07/2021] [Indexed: 12/24/2022] Open
Abstract
Purpose Infliximab, which was approved in 2002, had its first biosimilar launched in 2014 across Japan. However, the penetration rate of this biosimilar remains unclear given the limited data regarding its current clinical use throughout Japan. This study was conducted to describe the current clinical characteristics of patients receiving infliximab and the penetration rate of the reference infliximab and/or biosimilar infliximab using a Japanese administrative claims database. Patients and Methods This retrospective, descriptive study utilized the Japan Medical Data Vision database, a nationwide hospital-based database. Data on patients receiving infliximab recorded from April 2008 to March 2019 were extracted from the database. Patient characteristics of the reference and biosimilar infliximab groups and penetration rates according to fiscal year, target diseases diagnosis, and subsidy for intractable diseases were examined. Results A total of 9735 patients were extracted for analysis, among whom 92% (n=8950) and 8% (n=785) received only reference infliximab and its biosimilar, respectively. Both groups exhibited similar clinical characteristics. The biosimilar penetration rate increased from 0.8% in 2014 to 22.5% in 2018, with overall penetration rates throughout the period according to diagnosis (with or without subsidy) being 14.4% (with, 4.1%; without, 16.4%), 4.7% (with, 3.7%; without, 10.6%), 5.7% (with, 4.5%; without, 13.5%), and 7.5% (with, 4.4%; without, 8.2%) for rheumatoid arthritis, Crohn’s disease, ulcerative colitis, and psoriasis, respectively. Conclusion Biosimilar infliximab is prescribed for patients with similar characteristics to reference infliximab. Despite the increasing penetration rates according to target disease, they remain much lower among patients receiving subsidy for intractable disease than among those who do not.
Collapse
Affiliation(s)
- Tsugumi Matsumoto
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.,Inflammation and Immunology Therapeutic Area Medical Affairs, Pfizer Japan Inc., Tokyo, Japan
| | - Takanori Tsuchiya
- Patient Impact Analysis, Outcome & Evidence, Corporate Affairs Health and Values, Pfizer Japan Inc., Tokyo, Japan
| | | | | | | | - Jiro Takata
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| |
Collapse
|
|
31
|
Hagymási K. The Nobel Prize in Physiology or Medicine-2020. Struct Chem 2021; 32:909-913. [PMID: 33584076 PMCID: PMC7870777 DOI: 10.1007/s11224-021-01731-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 01/12/2021] [Indexed: 11/29/2022]
Abstract
At the time of COVID-19 coronavirus pandemia, the Nobel Prize of Physiology or Medicine 2020 was awarded jointly to three researchers Harvey J. Alter, Charles M. Rice, and Michael Houghton for the discovery of Hepatitis C virus. Their works contributed to the isolation of the blood-borne virus, causing chronic hepatitis in 80% of infected person, resulting in cirrhosis, and in elevated risk of liver failure and hepatocellular carcinoma formation. Their results created the basis of HCV screening of blood, and blood products, achieving more than 95% cure of infected people without nearly side effects with direct-acting antiviral agents, supporting the goal of the WHO targeting the elimination of viral hepatitis by 2030.
Collapse
Affiliation(s)
- Krisztina Hagymási
- 1st Department of Surgery and Interventional Gastroenterology, Semmelweis University, Budapest, Hungary
| |
Collapse
|