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Last update 08 May 2025

RNA-directed RNA polymerase L

Last update 08 May 2025

Basic Info

Synonyms-

Introduction-

Drugs associated with RNA-directed RNA polymerase L

Lumicitabine

Target

RNA-directed RNA polymerase L

Mechanism

RNA-directed RNA polymerase L inhibitors

Active Org.-

Originator Org.

Johnson & Johnson

Active Indication-

Inactive Indication

Asthma [+2]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with RNA-directed RNA polymerase L

NCT03502694

/ WithdrawnPhase 2

A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine (JNJ-64041575) Regimens in Hospitalized Adult Subjects Infected With Human Metapneumovirus

The purpose of this study is to determine in hospitalized adult participants infected with human metapneumovirus (hMPV - a virus closely related to respiratory syncytial virus (RSV) and has been identified as an important cause of acute respiratory infections, affecting all age groups) the dose-response relationship of multiple regimens of lumicitabine on antiviral activity based on nasal hMPV shedding using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay.

Start Date05 Nov 2018

Sponsor / Collaborator

Janssen Research & Development LLC

JPRN-JapicCTI-184013

/ Unknown statusPhase 2

Start Date06 Jul 2018

Sponsor / Collaborator

Janssen Pharmaceuticals, Inc.

JPRN-jRCT2080223955

/ Unknown statusPhase 2

Start Date25 Jun 2018

Sponsor / Collaborator

Janssen Pharmaceuticals, Inc.

100 Clinical Results associated with RNA-directed RNA polymerase L

100 Translational Medicine associated with RNA-directed RNA polymerase L

0 Patents (Medical) associated with RNA-directed RNA polymerase L

Literatures (Medical) associated with RNA-directed RNA polymerase L

01 May 2025·Journal of Molecular Graphics and Modelling

Computational study of interaction of calixarene with ebola virus structural proteins and its potential therapeutic implications

Article

Author: Maity, Atanu ; Dutta, Tanmoy ; Alomary, Mohammad N ; Alharbi, Ali H ; Jamal, Qazi Mohammad Sajid ; Jamous, Yahya F ; Ahmad, Varish ; Ansari, Mohammad Azam

Ebola virus (EBOV) is a negative-strand RNA virus that causes hemorrhagic fever and fatal illness in humans. According to WHO, the Ebola virus caused 28,646 fatal cases and 11,323 deaths in West Africa due to hemorrhagic fever and deadly disease in humans between 2013 and 2016. Between 1976 and 2022, approximately 15,409 fatalities caused by EBOV took place worldwide. Unfortunately, no effective vaccine or drugs are available to prevent this deadly disease. In the present study, State-of-the-art tools based on in-silico methods were used to elucidate the interaction pattern of calixarene (CAL) with seven EBOV structural proteins, i.e., GP1,2, nucleoprotein (NP), polymerase cofactor (VP35), (VP40), transcription activator (VP30), VP24, and RNA-dependent RNA polymerase (L). CAL is a cage-like compound with supramolecular features. The molecular docking lead analysis using AutoDock tool has been performed to find out the binding pattern of CAL with EBOV proteins. Obtained results revealed efficient inhibitory properties of calixarene (CAL) against seven Ebola virus structural proteins i.e., GP1,2, nucleoprotein (NP), polymerase cofactor (VP35), (VP40), transcription activator (VP30), VP24, and RNA-dependent RNA polymerase (L). Molecular docking analysis shows that the interaction of CAL with VP24 was highest with the total binding energy -12.47 kcal/mol and 26.90 nM inhibitions constant. Molecular Dynamics study has also quantified the efficiency of CAL against VP24. In conclusion, the present study suggests that CAL and its derivatives could be used as inhibitors to counter EBOV infection. Furthermore, in vitro and in vivo laboratory experimentation is required to establish CAL and its derivatives as a potential inhibitor against EBOV.

22 Oct 2024·Journal of Virology

Architectural organization and in situ fusion protein structure of lymphocytic choriomeningitis virus

Article

Author: Lyles, Kristin Van Mouwerik ; Zhou, Kang ; Zhou, Z. Hong ; Kang, Joon S. ; Luo, Ming ; Wang, Hui ; Tang, Sijia

ABSTRACT Arenaviruses exist globally and can cause hemorrhagic fever and neurological diseases, exemplified by the zoonotic pathogen lymphocytic choriomeningitis virus (LCMV). The structures of individual LCMV proteins or their fragments have been reported, but the architectural organization and the nucleocapsid assembly mechanism remain elusive. Importantly, the in situ structure of the arenavirus fusion protein complex (glycoprotein complex, GPC) as present on the virion prior to fusion, particularly with its integral stable signal peptide (SSP), has not been shown, hindering efforts such as structure-based vaccine design. Here, we have determined the in situ structure of LCMV proteins and their architectural organization in the virion by cryogenic electron tomography. The tomograms reveal the global distribution of GPC, matrix protein Z, and the contact points between the viral envelope and nucleocapsid. Subtomogram averaging yielded the in situ structure of the mature GPC with its transmembrane domain intact, revealing the GP2-SSP interface and the endodomain of GP2. The number of RNA-dependent RNA polymerase L molecules packaged within each virion varies, adding new perspectives to the infection mechanism. Together, these results delineate the structural organization of LCMV and offer new insights into its mechanism of LCMV maturation, egress, and cell entry. IMPORTANCE The impact of COVID-19 on public health has highlighted the importance of understanding zoonotic pathogens. Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne human pathogen that causes hemorrhagic fever. Herein, we describe the in situ structure of LCMV proteins and their architectural organization on the viral envelope and around the nucleocapsid. The virion structure reveals the distribution of the surface glycoprotein complex (GPC) and the contact points between the viral envelope and the underlying matrix protein, as well as the association with the nucleocapsid. The morphology and sizes of virions, as well as the number of RNA polymerase L inside each virion vary greatly, highlighting the fast-changing nature of LCMV. A comparison between the in situ GPC trimeric structure and prior ectodomain structures identifies the transmembrane and endo domains of GPC and key interactions among its subunits. The work provides new insights into LCMV assembly and informs future structure-guided vaccine design.

01 Dec 2023·Journal of Genetic Engineering and Biotechnology

Immunoinformatics-aided rational design of multiepitope-based peptide vaccine (MEBV) targeting human parainfluenza virus 3 (HPIV-3) stable proteins

Article

Author: Uddin, Md Jasim ; Halder, Sajal Kumar ; Abdullah-Al-Mamun, M ; Hossen, Md Sakib ; Haque, Munima ; Al Arian, Tawsif ; Shakil, Md Salman ; Hasan, Md Nazmul

AbstractBackgroundHuman parainfluenza viruses (HPIVs) are common RNA viruses responsible for respiratory tract infections. Human parainfluenza virus 3 (HPIV-3) is particularly pathogenic, causing severe illnesses with no effective vaccine or therapy available.ResultsThe current study employed a systematic immunoinformatic/reverse vaccinology approach to design a multiple epitope-based peptide vaccine against HPIV-3 by analyzing the virus proteome. On the basis of a number of therapeutic features, all three stable and antigenic proteins with greater immunological relevance, namely matrix protein, hemagglutinin neuraminidase, and RNA-directed RNA polymerase L, were chosen for predicting and screening suitable T-cell and B-cell epitopes. All of our desired epitopes exhibited no homology with human proteins, greater population coverage (99.26%), and high conservancy among reported HPIV-3 isolates worldwide. All of the T- and B-cell epitopes are then joined by putative ligands, yielding a 478-amino acid-long final construct. Upon computational refinement, validation, and thorough screening, several programs rated our peptide vaccine as biophysically stable, antigenic, allergenic, and non-toxic in humans. The vaccine protein demonstrated sufficiently stable interaction as well as binding affinity with innate immune receptors TLR3, TLR4, and TLR8. Furthermore, codon optimization and virtual cloning of the vaccine sequence in a pET32a ( +) vector showed that it can be readily expressed in the bacterial system.ConclusionThe in silico designed HPIV-3 vaccine demonstrated potential in evoking an effective immune response. This study paves the way for further preclinical and clinical evaluation of the vaccine, offering hope for a future solution to combat HPIV-3 infections.

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RNA-directed RNA polymerase L

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