Potential antiviral options against SARS-CoV-2 infection
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Abstract
As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6,5 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified most potent sera from recovered patients for treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that combinations of virus-directed nelfinavir along with host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.
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SciScore for 10.1101/2020.05.12.091165: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: The patients gave their informed consent through the koronastudien.no website.
IRB: The study was approved by national ethical committee (clinical trial: NCT04320732; REK: 124170). 2.1.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell cultures: Human telomerase reverse transcriptase-immortalized retinal pigment epithelial RPE, lung adenocarcinoma A427, non-small-cell lung cancer Calu-3 and epithelial colorectal adenocarcinoma Caco-2 cells were grown in DMEM-F12 medium supplemented … SciScore for 10.1101/2020.05.12.091165: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: The patients gave their informed consent through the koronastudien.no website.
IRB: The study was approved by national ethical committee (clinical trial: NCT04320732; REK: 124170). 2.1.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell cultures: Human telomerase reverse transcriptase-immortalized retinal pigment epithelial RPE, lung adenocarcinoma A427, non-small-cell lung cancer Calu-3 and epithelial colorectal adenocarcinoma Caco-2 cells were grown in DMEM-F12 medium supplemented with 100 μg/mL streptomycin and 100 U/mL penicillin (Pen/Strep), 2 mM L-glutamine, 10% FBS, and 0.25% sodium bicarbonate (Sigma-Aldrich, St. Louis, USA). Caco-2suggested: NoneHuman large-cell lung carcinoma NCI-H460, colon cancer SW620, colorectal carcinoma SW480 and HT29 cells were grown in RPMI medium supplied with 10% FBS and Pen-Strep. NCI-H460suggested: NoneSW480suggested: NoneHT29suggested: NoneHuman adenocarcinoma alveolar basal epithelial A549, human embryonic kidney HEK-293 cells and kidney epithelial cells extracted from an African green monkey (Vero-E6) were grown in DMEM medium supplemented with 10% FBS and Pen-Strep. A549suggested: NoneHEK-293suggested: None200 μl of nasopharyngeal swabs (NPS) in universal transport medium were diluted 5 times in culture medium (DMEM) supplemented with 0.2% bovine serum albumin (BSA), 0.6 μg/mL penicillin, 60 μg/mL streptomycin, and 2 mM L-glutamine and inoculated into Vero E6 cells. Vero E6suggested: RRID:CVCL_XD71)Table S1: Compounds, their suppliers, catalogue numbers and AUCs; Table S2: Results of neutralization and ELISA assays; Figure S1: Propagation of HCoV-19/Norway/Trondheim-E9/2020 in cell cultures; Figure S2: Effect of temperature and UV radiation on infectivity of HCoV-19/Norway/Trondheim-E9/2020 strain; Figure S3: The effect of serum from patient recovered from SARS-CoV-2 infection on viability of Vero-E6 cells infected with 7 SARS-CoV-2 strains; Figure S4: Comparison of anti-SARS-CoV-2 activities of amodiaquine and its analogues. Vero-E6suggested: NoneSoftware and Algorithms Sentences Resources Reads were aligned using the Bowtie 2 software package version 2.3.4.1 to the reference viral genome Wuhan-Hu-1/2019. Bowtie 2suggested: (Bowtie 2, RRID:SCR_016368)The consensus FASTQ sequences were obtained with bcftools and vcfutils.pl (from SAMtools) and converted to FASTA using seqtk (https://github.com/lh3/seqtk). SAMtoolssuggested: (SAMTOOLS, RRID:SCR_002105)Drug and serum sensitivity quantification: The half-maximal cytotoxic concentration (CC50) for each compound was calculated based on viability/death curves obtained on mock-infected cells after non-linear regression analysis with a variable slope using GraphPad Prism software version 7.0a (GraphPad Software, CA, USA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)The expected responses were calculated based on ZIP reference model using SynergyFinder web-application, version 2 [80]. 2.10. SynergyFindersuggested: (SynergyFinder, RRID:SCR_019318)2.11. https://sars-coronavirus-2.info/ website: We reviewed the current landscape of available diagnostic tools, as well as emerging treatment and prophylactic options for the SARS-CoV-2 pandemic and have summarized the information in a database that can be freely accessed at https://sars-coronavirus-2.info. The information in the database was obtained from PubMed, clinicaltrials.gov, DrugBank, DrugCentral, Chinese Clinical Trials Register (ChiCTR), and EU Clinical Trials Register databases [25–27] as well as other public sources. PubMedsuggested: (PubMed, RRID:SCR_004846)DrugBanksuggested: (DrugBank, RRID:SCR_002700)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04252664 Suspended A Trial of Remdesivir in Adults With Mild and Moderate COVID… NCT0425487 Trial number did not resolve on clinicaltrials.gov. Is the number correct? NA NCT04255017 Recruiting A Prospective/Retrospective,Randomized Controlled Clinical S… NCT04261517 Completed Efficacy and Safety of Hydroxychloroquine for Treatment of C… NCT04260594 Not yet recruiting Clinical Study of Arbidol Hydrochloride Tablets in the Treat… NCT04320732 Recruiting Risk Factors for Community- and Workplace Transmission of CO… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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