#Transcriptome-based #drug #repositioning for #coronavirus disease 2019 (#COVID19) (Pathog Dis., abstract)

[Source: Pathogens and Disease, full page: (LINK). Abstract, edited.]

Transcriptome-based drug repositioning for coronavirus disease 2019 (COVID-19)

Zhilong Jia, Xinyu Song, Jinlong Shi, Weidong Wang, Kunlun He

Pathogens and Disease, ftaa036, https://doi.org/10.1093/femspd/ftaa036

Published: 15 July 2020

 

Abstract

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has led to a pandemic with high morbidity and mortality. However, there are no effective drugs to prevent and treat the disease. Transcriptome-based drug repositioning, identifying new indications for old drugs, is a powerful tool for drug development. Using bronchoalveolar lavage fluid transcriptome data of COVID-19 patients, we found that the endocytosis and lysosome pathways are highly involved in the disease and that the regulation of genes involved in neutrophil degranulation was disrupted, suggesting an intense battle between SARS-CoV-2 and humans. Furthermore, we implemented a coexpression drug repositioning analysis, cogena, and identified two antiviral drugs (saquinavir and ribavirin) and several other candidate drugs (such as dinoprost, dipivefrine, dexamethasone and (-)-isoprenaline). Notably, the two antiviral drugs have also previously been identified using molecular docking methods, and ribavirin is a recommended drug in the diagnosis and treatment protocol for COVID pneumonia (trial version 5–7) published by the National Health Commission of the P.R. of China. Our study demonstrates the value of the cogena-based drug repositioning method for emerging infectious diseases, improves our understanding of SARS-CoV-2-induced disease, and provides potential drugs for the prevention and treatment of COVID-19 pneumonia.

SARS-CoV-2, COVID-19, drug repositioning, neutrophil degranulation, saquinavir, ribavirin

Issue Section: Research article

This content is only available as a PDF.

© FEMS 2020.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Antivirals; Ribavirin; Saquinavir.

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#Clinical #trials of repurposed #antivirals for #SARS-CoV-2 (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Clinical trials of repurposed antivirals for SARS-CoV-2

Miguel Angel Martinez

DOI: 10.1128/AAC.01101-20

 

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.

Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Keywords: SARS-CoV-2; COVID-19; Antivirals; Chloroquine; Lopinavir/Ritonavir; Ribavirin; Favipiravir; Remdesivir.

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Effect of #combination #antiviral #therapy on #hematological profiles in 151 adults hospitalized with #severe #coronavirus disease 2019 (Pharmacol Res., abstract)

[Source: Pharmacological Research, full page: (LINK). Abstract, edited.]

Pharmacological Research | Volume 160, October 2020, 105036

Effect of combination antiviral therapy on hematological profiles in 151 adults hospitalized with severe coronavirus disease 2019

Xin Li a,1, Yi Yang b,1, Lancong Liu b, Xuefeng Yang d, Xiaobo Zhao a, Yan Li d, Yanyan Ge d, Yuxin Shi d, Ping Lv d, Jianchu Zhang e, Tao Bai f, Hua Zhou b, Pei Luo b,g, Shilong Huang c

a Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China; b State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, PR China; c Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, PR China; d Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Avenue, Wuhan, Hubei, 430030, PR China; e Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430030, PR China; f Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430030, PR China; g Guangdong-Hongkong-Macau Joint Laboratory of Collaborative Innovation for Environmental Quality, PR China

Received 30 April 2020, Revised 7 June 2020, Accepted 16 June 2020, Available online 18 June 2020.

DOI: https://doi.org/10.1016/j.phrs.2020.105036

 

Abstract

Objectives

The current diagnosis and medicines approach in coronavirus disease 2019 (COVID-19) does not reflect the heterogeneous characteristics of this disease. This study aims to find a new antiviral combination regimen by investigating the frequency of clinically relevant and objectively identified comorbidities, and the clustering of these clinical syndromes and varying results of treatment with antiviral drugs in patients hospitalized with severe COVID-19.

Methods

This study recruited 151 severe COVID-19 infection cases diagnosed in our hospital examination and illustrated the clinical potential during a consecutive 25-day medication period. Potential differences in disease severity and clinical characteristics, hematological profile, and current pharmacologic treatments (single agent, double or triple combinations, and the combined antiviral drugs plus Lianhua Qingwen) among comorbidity clusters were explored.

Results

Although disease severity was comparable among three clusters, it was markedly different in terms of laboratory test status. Coagulable abnormality was mainly present in cluster 1 and cluster 2. Other indicators were normal, except for a significant increase of neutrophils presented in cluster 2. Patients showed the most complicated haematological results in cluster 3, including severe coagulation abnormalities, leukocytosis, neutrophilic granulocytosis, and lymphopenia. Our results for the first time suggest that a quadruple combination therapy (Ribavirin, Lopinavir/ritonavir, Umifenovir, and Lianhua Qingwen) can be considered as a preferred treatment approach to severe COVID-19 patients. After treatment, abnormal coagulation and leukocyte had markedly improved with a better prognosis.

Conclusion

This study expands the understanding of the co-occurrence of combination therapy in patients with COVID-19, which provides the probability of developing novel combined therapy. Furthermore, explore clinical trials of variable antivirus treatments based on subgroup analyses or on using subgroups in the selection criteria would be the next step.

Keywords: SARS-CoV-2; COVID-19; Antivirals; Lopinavir/Ritonavir; Arbidol; China.

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Triple #combination of #interferon beta-1b, #lopinavir–ritonavir, and #ribavirin in the #treatment of patients admitted to #hospital with #COVID19: an open-label, randomised, phase 2 trial (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial

Prof Ivan Fan-Ngai Hung, MD, Kwok-Cheung Lung, FRCP, Eugene Yuk-Keung Tso, FRCP, Raymond Liu, FRCP, Tom Wai-Hin Chung, MRCP, Man-Yee Chu, MRCP, Yuk-Yung Ng, MRCP, Jenny Lo, MRCP, Jacky Chan, MRCP, Anthony Raymond Tam, MRCP, Hoi-Ping Shum, MD, Veronica Chan, FRCP, Alan Ka-Lun Wu, FRCPath, Kit-Man Sin, FRCP,  Wai-Shing  Leung, MRCP, Wai-Lam Law, FRCP, David Christopher Lung, FRCPath, Simon Sin, FRCP, Pauline Yeung, MRCP, Cyril Chik-Yan Yip, PhD, Ricky Ruiqi Zhang, PhD, Agnes Yim-Fong Fung, BSc, Erica Yuen-Wing Yan, MSc, Kit-Hang Leung, MSc, Jonathan Daniel Ip, MSc,
Allen Wing-Ho Chu, MSc, Wan-Mui Chan, PhD, Anthony Chin-Ki Ng, BSc, Rodney Lee, FRCPA, Kitty Fung, FRCPA, Alwin Yeung, FRCP, Tak-Chiu Wu, FRCP, Johnny Wai-Man Chan, FRCP, Wing-Wah Yan, FRCP, Wai-Ming Chan, FRCP, Jasper Fuk-Woo Chan, MD, Albert Kwok-Wai Lie, FRCP, Owen Tak-Yin Tsang, FRCP, Vincent Chi-Chung Cheng, MD, Tak-Lun Que, FRCPath, Prof Chak-Sing Lau, MD, Kwok-Hung Chan, PhD, Kelvin Kai-Wang To, MD, Prof Kwok-Yung Yuen, MD

Published: May 08, 2020 | DOI: https://doi.org/10.1016/S0140-6736(20)31042-4

 

Summary

Background

Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ribavirin for treating patients with COVID-19.

Methods

This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688.

Findings

Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5–11]) than the control group (12 days [8–15]; hazard ratio 4·37 [95% CI 1·86–10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study.

Interpretation

Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted.

Funding

The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.

Keywords: SARS-CoV-2; COVID-19; Antivirals; Lopinavir; Ritonavir; Ribavirin; Interferons.

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#Coronavirus Disease 2019 in #Children: Characteristics, #Antimicrobial #Treatment, and #Outcomes (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology | Available online 7 May 2020, 104425 | In Press, Journal Pre-proof

Coronavirus Disease 2019 in Children: Characteristics, Antimicrobial Treatment, and Outcomes

Hui Peng 1, Ping Gao 1, Qiong Xu, Maochang Liu, Jing Peng, Yang Wang, Hua Xu

Department of Clinical Pharmacology, Wuhan children’s hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

Received 26 March 2020, Revised 27 April 2020, Accepted 4 May 2020, Available online 7 May 2020.

DOI: https://doi.org/10.1016/j.jcv.2020.104425

 

Highlights

  • The severity of COVID-19 in pediatric cases was milder than adults.
  • Children younger than 2 years were more susceptible to COVID-19.
  • The average length of stay and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively.

 

Abstract

Background

At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help paediatricians To help pediatricians understand the conditions of COVID-19 in children, we conducted this study.

Methods

We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan children’s hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes.

Results

As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-α nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance.

Conclusions

The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.

Keywords: SARS-CoV-2; COVID-19; Hubei; China; Antivirals; Arbidol; Ribavirin; Interferons.

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#Efficacy and #Safety of Current #Therapeutic #Options for #COVID19 – #Lessons to Be Learnt From #SARS and #MERS #Epidemic: A Systematic Review and Meta-Analysis (Pharmacol Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pharmacol Res. 2020 Apr 30;104872. doi: 10.1016/j.phrs.2020.104872. Online ahead of print.

Efficacy and Safety of Current Therapeutic Options for COVID-19 – Lessons to Be Learnt From SARS and MERS Epidemic: A Systematic Review and Meta-Analysis

Han Zhong 1, Yan Wang 2, Zai-Li Zhang 3, Yang-Xi Liu 3, Ke-Jia Le 3, Min Cui 3, Yue-Tian Yu 4, Zhi-Chun Gu 5, Yuan Gao 6, Hou-Wen Lin 7

Affiliations: 1 Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China; Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. 2 Department of Pharmacy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi, China. 3 Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. 4 Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. Electronic address: fishyyt@sina.com. 5 Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. Electronic address: guzhichun213@163.com. 6 Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. 7 Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. Electronic address: franklin67@163.com.

PMID: 32360583 DOI: 10.1016/j.phrs.2020.104872

 

Abstract

The rapidly progressing of coronavirus disease 2019 (COVID-19) pandemic has become a global concern. This meta-analysis aimed at evaluating the efficacy and safety of current option of therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) besides COVID-19, in an attempt to identify promising therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WANFANG DATA for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies that evaluated therapies (hydroxychloroquine, lopinavir/ritonavir-based therapy, and ribavirin-based therapy, etc.) for SARS, MERS, and COVID-19. The primary outcomes were mortality, virological eradication and clinical improvement, and secondary outcomes were improvement of symptoms and chest radiography results, incidence of acute respiratory disease syndrome (ARDS), utilization of mechanical ventilation, and adverse events (AEs). Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was appraised using GRADEpro. Eighteen articles (5 RCTs, 2 prospective cohort studies, and 11 retrospective cohort studies) involving 4,941 patients were included. Compared with control treatment, anti-coronary virus interventions significantly reduced mortality (RR 0.65, 95% CI 0.44-0.96; I2 = 81.3%), remarkably ameliorate clinical improvement (RR 1.52, 95% CI 1.05-2.19) and radiographical improvement (RR 1.62, 95% CI 1.11-2.36, I2 = 11.0 %), without manifesting clear effect on virological eradication, incidence of ARDS, intubation, and AEs. Subgroup analyses demonstrated that the combination of ribavirin and corticosteroids remarkably decreased mortality (RR 0.43, 95% CI 0.27-0.68). The lopinavir/ritonavir-based combination showed superior virological eradication and radiographical improvement with reduced rate of ARDS. Likewise, hydroxychloroquine improved radiographical result. For safety, ribavirin could induce more bradycardia, anemia and transaminitis. Meanwhile, hydroxychloroquine could increase AEs rate especially diarrhea. Overall, the quality of evidence on most outcomes were very low. In conclusion, although we could not draw a clear conclusion for the recommendation of potential therapies for COVID-19 considering the very low quality of evidence and wide heterogeneity of interventions and indications, our results may help clinicians to comprehensively understand the advantages and drawbacks of each anti-coronavirus agents on efficacy and safety profiles. Lopinavir/ritonavir combinations might observe better virological eradication capability than other anti-coronavirus agents. Conversely, ribavirin might cause more safety concerns especially bradycardia. Thus, large RCTs objectively assessing the efficacy of antiviral therapies for SARS-CoV-2 infections should be conducted with high priority.

Keywords: COVID-19; MERS; SARS; efficacy; safety; therapeutic options.

Copyright © 2020. Published by Elsevier Ltd.

Conflict of interest statement

Declaration of Competing Interest: None conflicts of interest to declare.

Keywords: SARS-CoV-2; COVID-19; SARS; MERS-CoV; Antivirals; Ribavirin; Chloroquine; Ritonavir; Lopinavir.

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#Pharmacokinetics-Pharmacodynamics of #Antiviral Agents Used to Treat #SARS-CoV-2 and Their Potential #Interaction with #Drugs and Other Supportive Measures: … (SSRN, abstract)

[Source: SSRN, full page. (LINK). Abstract, edited.]

Pharmacokinetics-Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures: a Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents

187 Pages Posted: 10 Apr 2020

Markus Zeitlinger, Medical University of Vienna; Birgit CP Koch, Erasmus University Rotterdam (EUR) – Erasmus Medical Center (MC); Roger Brüggemann, Radboud University Nijmegen – Radboud University Medical Center; Pieter De Cock, Ghent University – Ghent University Hospital; Timothy Felton, University of Manchester; Maya Hites, Université Libre de Bruxelles (ULB); Jennifer Le, University of California, San Diego (UCSD) – Skaggs School of Pharmacy and Pharmaceutical Sciences; Sonia Luque, Hospital del Mar; Alasdair MacGowan, Southmead Hospital; Deborah Marriott, University of New South Wales (UNSW) – St Vincent’s Hospital; Anouk E Muller, Erasmus University Rotterdam (EUR) – Erasmus Medical Center (MC); Kristina Nadrah, University of Ljubljana – University Medical Centre Ljubljana; David Paterson, University of Queensland; Joseph F. Standing, University College London – Great Ormond Street Institute of Child Health; João P. Telles, AC Camargo Cancer Center; Michael Wölfl-Duchek, Medical University of Vienna; Michael Thy, Hopital Bichat Claude Bernard; Jason  A. Roberts, University of Queensland

Date Written: March 23, 2020

 

Abstract

There is an urgent need to identify optimal antiviral therapies for COVID-19 caused by SARS-CoV-2. We have conducted a rapid comprehensive review to examine antiviral pharmacology evidence, focussing on i) the pharmacokinetics (PK) of available or proposed therapies; ii) coronavirus-specific pharmacodynamics (PD); iii) PK and PD interactions between proposed combination therapies; iv) a review of the pharmacology of major supportive therapies; and v) a summary of anticipated drug-drug interactions (DDIs). We found promising in vitro evidence for remdesivir, (hydroxy)chloroquine and favipiravir against SARS-CoV-2; potential clinical benefit in SARS-CoV-2 with the combination of lopinavir-ritonavir (LPV/r) plus ribavirin; and strong evidence for LPV/r plus ribavirin against MERS for post-exposure prophylaxis in healthcare workers. Despite these emerging data, robust controlled clinical trials remain imperative. These antiviral therapies should be used with caution in the light of the significant drug interactions and the need to evaluate optimal doses for treating mild versus serious infections.

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Note: Funding: No funding was received for this manuscript.

Conflict of Interest: The authors declare that they have no conflict of interest associated with the content of the current manuscript.

Keywords: Coronavirus, DDI, Intensive Care, repurposing, off-label, PK/PD, SARS-CoV-2

Suggested Citation: Zeitlinger, Markus and Koch, Birgit CP and Brüggemann, Roger and De Cock, Pieter and Felton, Timothy and Hites, Maya and Le, Jennifer and Luque, Sonia and MacGowan, Alasdair and Marriott, Deborah and Muller, Anouk E and Nadrah, Kristina and Paterson, David and Standing, Joseph F. and Telles, João P. and Wölfl-Duchek, Michael and Thy, Michael and Roberts, Jason A., Pharmacokinetics-Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures: a Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents (March 23, 2020). Available at SSRN: https://ssrn.com/abstract=3561236 or http://dx.doi.org/10.2139/ssrn.3561236

Keywords: SARS-CoV-2; COVID-19; Antivirals.

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#Remdesivir, #lopinavir, #emetine, and homoharringtonine inhibit #SARS-CoV-2 #replication #invitro (Antiviral Res., abstract)

[Source: Antiviral Research, full page: (LINK). Abstract, edited.]

Antiviral Research | Available online 3 April 2020, 104786 | In Press, Journal Pre-proof  | Short Communication

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

Ka-Tim Choy 1, Alvina Yin-Lam Wong 1, Prathanporn Kaewpreedee 1, Sin-Fun Sia 1, Dongdong Chen 1, Kenrie Pui Yan Hui 1, Daniel Ka Wing Chu 1, Michael Chi Wai Chan 1, Peter Pak-Hang Cheung 2, Xuhui Huang 2, Malik Peiris 1, Hui-Ling Yen 1

{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

Received 15 March 2020, Revised 28 March 2020, Accepted 29 March 2020, Available online 3 April 2020.

DOI: https://doi.org/10.1016/j.antiviral.2020.104786

 

Highlights

  • Remdesivir inhibits SARS-CoV-2 replication in Vero-E6 cells with EC50 at 23.15 μM.
  • Lopinavir but not ritonavir inhibits SARS-CoV-2 replication with EC50 at 26.63 μM.
  • Homoharringtonine and emetine inhibits SARS-CoV-2 replication with EC50 at 2.55 and 0.46 μM, respectively.
  • Combination of remdesivir and emetine showed synergistic effect in vitro.

 

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.

Keywords: COVID-19 – remdesivir – lopinavir – ritonavir – emetine – homoharringtonine

Keywords: SARS-CoV-2; COVID-19; Antivirals; Remdesivir; Emetine.

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The #Correlation Between #Viral #Clearance and #Biochemical #Outcomes of 94 #COVID19 Infected Discharged Patients (Inflamm Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Inflamm Res 2020 Mar 29 [Online ahead of print]

The Correlation Between Viral Clearance and Biochemical Outcomes of 94 COVID-19 Infected Discharged Patients

Jing Yuan 1, Rougrong Zou 1, Lijiao Zeng 1, Shanglong Kou 1, Jianfeng Lan 1, Xiaohe Li 1, Yanhua Liang 1, Xiaoyan Ding 1, Guoyu Tan 1, Shenghong Tang 1, Lei Liu 1, Yingxia Liu 1, Yanchao Pan 2, Zhaoqin Wang 3

Affiliations: 1 Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People’s Hospital, Shenzhen, 518112, China. 2 Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People’s Hospital, Shenzhen, 518112, China. panychao@126.com. 3 Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People’s Hospital, Shenzhen, 518112, China. zhaoqinw108@126.com.

PMID: 32227274 DOI: 10.1007/s00011-020-01342-0

 

Abstract

Objective:

This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People’s Hospital, enrolled from Jan 5 to Feb 13, 2020.

Methods:

The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected.

Results:

COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin.

Conclusions:

Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.

Keywords: CK; COVID-19; Clearance ratio; LDH.

Keywords: SARS-CoV-2; COVID-19; Antivirals; Lopinavir; Ritonavir; Ribavirin.

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#Ribavirin, #Remdesivir, #Sofosbuvir, #Galidesivir, and #Tenofovir Against #SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp): A Molecular Docking Study (Life Sci., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Life Sci, 117592 2020 Mar 25 [Online ahead of print]

Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir Against SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp): A Molecular Docking Study

Abdo A Elfiky 1

Affiliation: 1 Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt. Electronic address: abdo@sci.cu.edu.eg.

PMID: 32222463 DOI: 10.1016/j.lfs.2020.117592

 

Abstract

Aims:

A new human coronavirus (HCoV), which has been designated SARS-CoV-2, began spreading in December 2019 in Wuhan City, China causing pneumonia called COVID-19. The spread of SARS-CoV-2 has been faster than any other coronaviruses that have succeeded in crossing the animal-human barrier. There is concern that this new virus will spread around the world as did the previous two HCoVs-Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)-each of which caused approximately 800 deaths in the years 2002 and 2012, respectively. Thus far, 11,268 deaths have been reported from the 258,842 confirmed infections in 168 countries.

Main methods:

In this study, the RNA-dependent RNA polymerase (RdRp) of the newly emerged coronavirus is modeled, validated, and then targeted using different anti-polymerase drugs currently on the market that have been approved for use against various viruses.

Key findings:

The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp. In addition, the results suggest guanosine derivative (IDX-184), Setrobuvir, and YAK as top seeds for antiviral treatments with high potential to fight the SARS-CoV-2 strain specifically.

Significance:

The availability of FDA-approved anti-RdRp drugs can help treat patients and reduce the danger of the mysterious new viral infection COVID-19. The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA.

Keywords: COVID-19; Drug repurposing; Molecular docking; RdRp; SARS-CoV-2; Structural bioinformatics.

Copyright © 2020. Published by Elsevier Inc.

Conflict of interest statement – Declaration of competing interest: The author declares that there is no competing interest in this work.

Keywords: SARS-CoV-2; COVID-19; Antivirals.

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