Antiviral Research

Raw data for SARS-CoV-2 inhibitors, polyether ionophores. Raw data includes CellTiter-Blue assay, cytopathy nuclei count and the following for morphological profiling: Full dose-response profiles and .R script to generate plots presented in the paper. plate00010_00013 is Vero E6 hTMPRSS2 cells plate00014_00017 is Vero E6 wild type cells Raw images for morphological profiling can be obtained upon request.

The is the processed data containing body temperature and viral loads of serum and tissues collected from animals that were passively immunized with neutralizing monoclonal antibodies and intradermally challenged with Japanese encephalitis virus.

The genetically diverse Orthocoronavirinae (CoV) family is prone to cross species transmission and disease emergence in both humans and livestock. Viruses similar to known epidemic strains circulating in wild and domestic animals further increase the probability of emergence in the future. Currently, there are no approved therapeutics for any human CoV presenting a clear unmet medical need. Remdesivir (RDV, GS-5734) is a monophosphoramidate prodrug of an adenosine analog with potent activity against an array of RNA virus families including Filoviridae, Paramyxoviridae, Pneumoviridae, and Orthocoronavirinae, through the targeting of the viral RNA dependent RNA polymerase (RdRp). We developed multiple assays to further define the breadth of RDV antiviral activity against the CoV family. Here, we show potent antiviral activity of RDV against endemic human CoVs OC43 (HCoV-OC43) and 229E (HCoV-229E) with submicromolar EC50 values. Of known CoVs, the members of the deltacoronavirus genus have the most divergent RdRp as compared to SARS- and MERS-CoV and both avian and porcine members harbor a native residue in the RdRp that confers resistance in beta-CoVs. Nevertheless, RDV is highly efficacious against porcine deltacoronavirus (PDCoV). These data further extend the known breadth and antiviral activity of RDV to include both contemporary human and highly divergent zoonotic CoV and potentially enhance our ability to fight future emerging CoV.

In silico docking of BVM and EP-39 on the hexameric crystal structure of the CACTD-SP1 Gag fragment

This file includes detailed descriptions of the methods used in this paper. It also includes an experimental section that details the synthesis and characterization of the compounds reported in this paper.

Sep 30, 2018 Dear Editors-in-Chief, Dr Gorisr Thank you so much for forwarding me the valuable reviewer’s comments. I have carefully addressed all of the issues raised by the referee as your comments. The manuscript was revised as follows (blue words): Reviewer 1 1. EMCV has four capsid proteins and eight non-structural proteins. In the study, only seven non-structural proteins were cloned into expression vectors and their inhibitions of IFN-β induction were studied. How were the other proteins? Reply: The comment is reasonable. It has been discussed in the fifth paragraph of DISSUSION 2. Luciferase assays results indicate 2C protein of EMCV affects inhibition of the type I IFN signaling pathway by MDA5 or RIG-I. However, the results of co-immunoprecipitation and confocal microscopy showed EMCV 2C only targets and interacts with MDA5. What is the possible mechanism of 2C protein inhibiting RIG-I-mediated IFN-β promoter activity? Reply: The comment is reasonable. It has been discussed at the end of the third paragraph of DISSUSION 3. Minor error, in page 9, line 368, the” (10-325)” should be deleted. Please check the full text carefully. Reply: The comment is reasonable. It has been correct. Reviewer 2 4. The introduction is an enumeration of facts, and not focused on the main studies of the paper. Sometimes is also misleading. For example, the sentence: “Nevertheless, whether EMCV regulates the innate immune response is not known.” Is incorrect, as there are described mechanisms how EMCV inhibits innate immune responses. Reply: The comment is correct. It has been addressed. 5. Most of the literature will now use the name MAVS, and not VISA. Reply: The comment is reasonable. It has been addressed. In addition, we have checked the full text carefully in grammar and spelling. The revised manuscript with modifications marked with red color is enclosed. We hope that it can be published as soon as possible. I am looking forward to hearing from you. Thanks! Sincerely, Juan Bai, PhD, Associated professor College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 P.R. China baijuan@njau.edu.cn

In vivo and in vitro studies

Dose response analyses of the inhibition of viral infectivity and cytotoxicity of the tested compounds