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The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 plays a pivotal role in the life cycle of the novel coronavirus and stands as a significant and promising target for anti-SARS-CoV-2 drugs. Non-nucleoside inhibitors (NNIs), as a category of compounds directed against SARS-CoV-2 RdRp, exhibit a unique and highly effective mechanism, effectively overcoming various factors contributing to drug resistance against nucleoside inhibitors (NIs). This review investigates various NNIs, including both natural and synthetic inhibitors, that closely interacting with the SARS-CoV-2 RdRp with valid evidences from in vitro and in silico studies.
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http://dx.doi.org/10.1016/j.biopha.2024.116180 | DOI Listing |
NAR Mol Med
July 2025
Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
The therapeutic value of antiviral nucleoside analogs was highlighted during the coronavirus disease 2019 (COVID-19) pandemic, with remdesivir and molnupiravir repurposed for their broad-spectrum antiviral activity. The cytidine analog azvudine (FNC) has recently gained attention as a potential treatment for human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the distinct substrate specificities of HIV-1 reverse transcriptase (RT) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), a unifying mechanism of inhibition remains elusive.
View Article and Find Full Text PDFViruses
August 2025
Department of Tropical Viral Vaccine Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
During the COVID-19 pandemic, the standard diagnostic assay for SARS-CoV-2 detection was RT-qPCR using TaqMan probes, with samples primarily taken through nasal and oropharyngeal swabs. The TaqMan-based method is costly, highlighting the need for a more affordable alternative for SARS-CoV-2 diagnosis. As an alternative strategy, we developed and evaluated a SYBR Green-based RT-qPCR method targeting the RNA-dependent RNA polymerase (RdRp) gene of SARS-CoV-2.
View Article and Find Full Text PDFPathogens
August 2025
Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Manila, Manila 1000, Philippines.
Natural products possess a wide range of biological and biochemical potentials, with plant-derived compounds being significant sources for discovering new drugs. In this study, extracts of and prepared with different solvents were tested for their antiviral activity against the original SARS-CoV-2 Wuhan strain and its variants using plaque assay, quantitative real time RT-PCR, and immunofluorescence assay (IFA). Our results showed that at their maximum non-toxic concentrations, Vitex-Dichloromethane (DCM) and Macaranga extracts significantly inhibited SARS-CoV-2 Wuhan strain growth in Vero E6 cells, showing a 5-log reduction in plaque assay and confirmed by IFA.
View Article and Find Full Text PDFEur Biophys J
August 2025
OPTMATLAB, Dipartimento Di Fisica, Università Di Genova, Via Dodecaneso 33, 16146, Genoa, Italy.
We characterized a DNA/gold interface designed for the detection of the SARS-CoV-2 RNA-dependent RNA polymerase/Helicase (RdRp/Hel) sequence. Using broadband spectroscopic ellipsometry (SE) and a difference spectra approach, we monitored molecular modifications at the interface, from probe sequence deposition to the insertion of a molecular spacer and subsequent hybridization with the target. The UV region revealed the characteristic DNA absorption peak around 260 nm, while changes in δΔ in the NIR correlated with increased optical thickness following each deposition step.
View Article and Find Full Text PDFBMC Infect Dis
July 2025
Institute for Health Technology Assessment., R. Ramiro Barcelos, 2350, 90035-903, Porto Alegre, Brazil.
Background: Pharmacological treatments for COVID-19 remain limited, particularly for severe outcomes. Tenofovir, an inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), has been proposed as a therapeutic agent to reduce hospitalization, intensive care unit (ICU) admissions, and mortality.
Objective: To assess the efficacy of tenofovir in COVID-19 patients based on randomized controlled trials (RCTs).