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      Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

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          Abstract

          An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.

          Highlights

          • •

            Remdesivir inhibits SARS-CoV-2 replication in Vero-E6 cells with EC 50 at 23.15 μM.

          • •

            Lopinavir but not ritonavir inhibits SARS-CoV-2 replication with EC 50 at 26.63 μM.

          • •

            Homoharringtonine and emetine inhibits SARS-CoV-2 replication with EC 50 at 2.55 and 0.46 μM, respectively.

          • •

            Combination of remdesivir and emetine showed synergistic effect in vitro.

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)
          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
          Article 0 comments Cited 10137 times – based on 0 reviews     Review now
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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

            Zunyou Wu, Jennifer M. McGoogan (2020)
            Article 0 comments Cited 8389 times – based on 0 reviews     Review now
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              Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

              Qun Li, Xuhua Guan, Peng Wu … (2020)
              Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
              Article 0 comments Cited 7062 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Hui-Ling Yen
                Journal
                Journal ID (nlm-ta): Antiviral Res
                Journal ID (iso-abbrev): Antiviral Res
                Title: Antiviral Research
                Publisher: Published by Elsevier B.V.
                ISSN (Print): 0166-3542
                ISSN (Electronic): 1872-9096
                Publication date PMC-release: 3 April 2020
                Publication date (Electronic): 3 April 2020
                Electronic Location Identifier: 104786
                Affiliations
                [1 ]School of Public Health, LKS Faculty of Medicine, The University of Hong Kong
                [2 ]Department of Chemistry, Hong Kong University of Science and Technology
                Author notes
                [∗ ]Corresponding author. hyen@ 123456hku.hk
                Article
                Publisher ID: S0166-3542(20)30200-X Publisher ID: 104786
                DOI: 10.1016/j.antiviral.2020.104786
                PMC ID: 7127386
                PubMed ID: 32251767
                SO-VID: ab52b23e-85b9-45f0-9fd1-224d89d9624d
                Copyright © © 2020 Published by Elsevier B.V.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 15 March 2020
                Date revision received : 28 March 2020
                Date accepted : 29 March 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: covid-19,remdesivir,lopinavir,ritonavir,emetine,homoharringtonine,abstract
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: covid-19, remdesivir, lopinavir, ritonavir, emetine, homoharringtonine, abstract

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