Over recent years, many outbreaks caused by (re)emerging RNA viruses have been reported worldwide, including life-threatening Flaviviruses, such as Dengue (DENV) and Zika (ZIKV). Currently, there is only one licensed vaccine against Dengue, Dengvaxia®. However, its administration is not recommended for children under nine years. Still, there are no specific inhibitors available to treat these infectious diseases. Among the flaviviral proteins, NS5 RNA-dependent RNA polymerase (RdRp) is a metalloenzyme essential for viral replication, suggesting that it is a promising macromolecular target since it has no human homolog. Nowadays, several NS5 RdRp inhibitors have been reported, while none inhibitors are currently in clinical development. In this context, this review constitutes a comprehensive work focused on RdRp inhibitors from natural, synthetic, and even repurposing sources. Furthermore, their main aspects associated with the structure-activity relationship (SAR), proposed mechanisms of action, computational studies, and other topics will be discussed in detail.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2021.113698 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efficacy and safety of SHEN26, a novel oral small molecular RdRp inhibitor for COVID-19 treatment: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial.
Virol J
January 2025
Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518118, China.
Background: SHEN26 (ATV014) is an oral RNA-dependent RNA polymerase (RdRp) inhibitor with potential anti-SARS-CoV-2 activity. Safety, tolerability, and pharmacokinetic characteristics were verified in a Phase I study. This phase II study aimed to verify the efficacy and safety of SHEN26 in COVID-19 patients.
View Article and Find Full Text PDFEvaluation of H1-Antihistamine as Potential Inhibitors of SARS-CoV-2 RNA-dependent RNA Polymerase: Repurposing Study of COVID-19 Therapy.
Turk J Pharm Sci
January 2025
Fenerbahçe University Faculty of Pharmacy, Department of Pharmaceutical Chemistry, İstanbul, Türkiye.
Introduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), from the family Coronaviridae, is the seventh known coronavirus to infect humans and cause acute respiratory syndrome. Although vaccination efforts have been conducted against this virus, which emerged in Wuhan, China, in December 2019 and has spread rapidly around the world, the lack of an Food and Drug Administration-approved antiviral agent has made drug repurposing an important approach for emergency response during the COVID-19 pandemic. The aim of this study was to investigate the potential of H1-antihistamines as antiviral agents against SARS-CoV-2 RNA-dependent RNA polymerase enzyme.
View Article and Find Full Text PDFIn silico evaluation of bisphosphonates identifies leading candidates for SARS-CoV-2 RdRp inhibition.
J Mol Graph Model
January 2025
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia; Department of Health Sciences, University of York, York, YO10 5DD, UK. Electronic address:
The novel coronavirus disease (COVID-19) pandemic has resulted in 777 million confirmed cases and over 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Post Acute Sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well.
View Article and Find Full Text PDFUnveiling the potential of Hamigeran-B from marine sponges as a probable inhibitor of Nipah virus RDRP through molecular modelling and dynamics simulation studies.
SAR QSAR Environ Res
December 2024
Department of Biotechnology, RV College of Engineering, Bengaluru, India.
The Nipah virus (NiV) is an emerging pathogenic paramyxovirus that causes severe viral infection with a high mortality rate. This study aimed to model the effectual binding of marine sponge-derived natural compounds (MSdNCs) towards RNA-directed RNA polymerase (RdRp) of NiV. Based on the functional relevance, RdRp of NiV was selected as the prospective molecular target and 3D-structure, not available in its native form, was modelled.
View Article and Find Full Text PDFIntegrated in Silico and in Vitro Studies of Rutin's Potential against SARS-CoV-2 through the Inhibition of the RNA-dependent RNA Polymerase.
Curr Med Chem
January 2025
Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt.
Article Synopsis
- Rutin was investigated as a potential inhibitor against SARS-CoV-2, showing strong binding and efficacy against the virus's RNA-dependent RNA polymerase (RdRp) protein.
- Structural similarity studies revealed that Rutin closely resembles Remdesivir, and molecular dynamics simulations confirmed that the RdRp-Rutin complex is more stable than the RdRp-Remdesivir complex.
- In vitro testing demonstrated that Rutin has a significantly lower inhibitory concentration (IC50) for RdRp compared to Remdesivir, indicating its superior effectiveness and a high safety margin.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!