For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
4
views
28
references
 Top references
cited by
0
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      523
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Remdesivir inhibits Porcine epidemic diarrhea virus infection in vitro

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious and pathogenic virus that causes symptoms such as diarrhea, vomiting, weight loss, and even death in piglets. Due to its high transmission rate, PEDV has resulted in significant global losses. Although some vaccines have been developed and utilized to prevent PEDV, their effectiveness is limited due to the virus's mutations. Therefore, it is imperative to investigate new strategies to combat PEDV. Remdesivir, a classic antiviral drug for coronaviruses, has been proven in our experiment to effectively suppress PEDV replication in Vero and LLC-PK1 cells. Additionally, the cell experiment demonstrated its direct inhibition of PEDV RNA-dependent RNA polymerase (RdRp) enzyme activity. Molecular docking simulations were employed to predict the binding site of remdesivir and PEDV RdRp. Moreover, we observed that remdesivir does not impact the production of inflammatory factors and exhibits antagonistic effects with exogenous nucleosides. Furthermore, we conducted RNA-Seq analysis to investigate the global changes in transcriptome of infected cells treated with remdesivir. Overall, our findings indicate that remdesivir holds promise as a potential candidate for the treatment of PEDV infection.

          Highlights

          • •

            Remdesivir inhibits PEDV infection in Vero cells and LLC-PK1 cells in a dose-dependent manner.

          • •

            Remdesivir effectively blocks PEDV replication.

          • •

            Remdesivir inhibits PEDV RNA-dependent RNA polymerase activity.

          • •

            Exogenous Nucleosides Attenuate Antiviral Effect of Remdesivir.

          • •

            Remdesivir could recovery the transcriptome changes caused by viral infection.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          A new coronavirus-like particle associated with diarrhea in swine

          M Pensaert, P. de Bouck (1978)
          Summary Coronavirus-like particles were detected by electron microscopy in the intestinal contents of pigs during a diarrheal outbreak on 4 swine breeding farms. Diarrhea was reproduced in experimental pigs with one of the isolates, designated CV777, which was found to be distinct from the 2 known porcine coronaviruses, transmissible gastroenteritis virus and hemagglutinating encephalomyelitis virus.
          Article 0 comments Cited 377 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir

            Egor P. Tchesnokov, Joy Y. Feng, Danielle P. Porter … (2019)
            Remdesivir (GS-5734) is a 1′-cyano-substituted adenosine nucleotide analogue prodrug that shows broad-spectrum antiviral activity against several RNA viruses. This compound is currently under clinical development for the treatment of Ebola virus disease (EVD). While antiviral effects have been demonstrated in cell culture and in non-human primates, the mechanism of action of Ebola virus (EBOV) inhibition for remdesivir remains to be fully elucidated. The EBOV RNA-dependent RNA polymerase (RdRp) complex was recently expressed and purified, enabling biochemical studies with the relevant triphosphate (TP) form of remdesivir and its presumptive target. In this study, we confirmed that remdesivir-TP is able to compete for incorporation with adenosine triphosphate (ATP). Enzyme kinetics revealed that EBOV RdRp and respiratory syncytial virus (RSV) RdRp incorporate ATP and remdesivir-TP with similar efficiencies. The selectivity of ATP against remdesivir-TP is ~4 for EBOV RdRp and ~3 for RSV RdRp. In contrast, purified human mitochondrial RNA polymerase (h-mtRNAP) effectively discriminates against remdesivir-TP with a selectivity value of ~500-fold. For EBOV RdRp, the incorporated inhibitor at position i does not affect the ensuing nucleotide incorporation event at position i+1. For RSV RdRp, we measured a ~6-fold inhibition at position i+1 although RNA synthesis was not terminated. Chain termination was in both cases delayed and was seen predominantly at position i+5. This pattern is specific to remdesivir-TP and its 1′-cyano modification. Compounds with modifications at the 2′-position show different patterns of inhibition. While 2′-C-methyl-ATP is not incorporated, ara-ATP acts as a non-obligate chain terminator and prevents nucleotide incorporation at position i+1. Taken together, our biochemical data indicate that the major contribution to EBOV RNA synthesis inhibition by remdesivir can be ascribed to delayed chain termination. The long distance of five residues between the incorporated nucleotide analogue and its inhibitory effect warrant further investigation.
            Article 0 comments Cited 281 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis

              Florian Kabinger, Carina Stiller, Jana Schmitzová … (2021)
              Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β- d - N 4 -hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp–RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir. Quantitative biochemical assays and high-resolution cryo-EM analysis reveal how the COVID-19 antiviral drug candidate molnupiravir causes lethal viral mutagenesis by the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2.
              Article 0 comments Cited 270 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Zhi-Biao Yang
                Zhe Wang
                Journal
                Journal ID (nlm-ta): Heliyon
                Journal ID (iso-abbrev): Heliyon
                Title: Heliyon
                Publisher: Elsevier
                ISSN (Electronic): 2405-8440
                Publication date PMC-release: 02 November 2023
                Publication date Collection: November 2023
                Publication date (Electronic): 02 November 2023
                Volume: 9
                Issue: 11
                Electronic Location Identifier: e21468
                Affiliations
                [a ]Shanghai Collaborative Innovation Center of Agri-Seeds / School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
                [b ]Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
                [c ]Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yang ling, Xianyang 712100, China
                Author notes
                [∗ ]Corresponding author. Shanghai Collaborative Innovation Center of Agri-Seeds / School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. wangz@ 123456sjtu.edu.cn
                [∗∗ ]Corresponding author. Shanghai Collaborative Innovation Center of Agri-Seeds / School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. zbyang@ 123456sjtu.edu.cn
                Article
                Publisher Item ID: S2405-8440(23)08676-0 Publisher ID: e21468
                DOI: 10.1016/j.heliyon.2023.e21468
                PMC ID: 10663732
                SO-VID: 7e7df993-31ab-4500-ba19-c80a91c8190a
                Copyright © © 2023 The Authors
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 2 July 2023
                Date revision received : 9 October 2023
                Date accepted : 21 October 2023
                Categories
                Subject: Research Article

                Keywords: porcine epidemic diarrhea virus,remdesivir,replication inhibition,rdrp,rna-seq
                Data availability:
                Keywords: porcine epidemic diarrhea virus, remdesivir, replication inhibition, rdrp, rna-seq

                Comments

                Comment on this article