The novel coronavirus Disease-2019 (COVID-19): Mechanism of action, detection and recent therapeutic strategies

Elahe Seyed Hosseini, Narjes Riahi Kashani, Hossein Nikzad, Javid Azadbakht, Hassan Hassani Bafrani, Hamed Haddad Kashani, Elahe Seyed Hosseini, Narjes Riahi Kashani, Hossein Nikzad, Javid Azadbakht, Hassan Hassani Bafrani, Hamed Haddad Kashani

Abstract

Novel coronavirus SARS-CoV-2, designated as COVID-19 by the World Health Organization (WHO) on the February 11, 2020, is one of the highly pathogenic β-coronaviruses which infects human. Early diagnosis of COVID-19 is the most critical step to treat infection. The diagnostic tools are generally molecular methods, serology and viral culture. Recently CRISPR-based method has been investigated to diagnose and treat coronavirus infection. The emergence of 2019-nCoV during the influenza season, has led to the extensive use of antibiotics and neuraminidase enzyme inhibitors, taken orally and intravenously. Currently, antiviral inhibitors of SARS and MERS spike proteins, neuraminidase inhibitors, anti-inflammatory drugs and EK1 peptide are the available therapeutic options for SARS-CoV-2 infected individuals. In addition, Chloroquine, which was previously used for malarial and autoimmune disease, has shown efficacy in the 2019-nCoV infection treatment. In severe hypoxaemia, a combination of antibiotics, α-interferon, lopinavir and mechanical ventilation can effectively mitigate the symptoms. Comprehensive knowledge on the innate and adaptive immune responses, will make it possible to propose potent antiviral drugs with their effective therapeutic measures for the prevention of viral infection. This therapeutic strategy will help patients worldwide to protect themselves against severe and fatal viral infections, that potentially can evolve and develop drug resistance, and to reduce mortality rates.

Keywords: Coronavirus; Immune response; Pathogen; Respiratory syndrome; Treatment.

Conflict of interest statement

The authors declared that they have no competing interests.

Copyright © 2020. Published by Elsevier Inc.

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Coronavirus structure. Coronaviruses are enveloped, non-segmented virus with a positive‐sense single‐stranded RNA and phosphorylated nucleocapsid (N) protein.
Fig. 2
Fig. 2
Phylogenetic analysis of whole genomes of SARS-CoV 2 and Pangolin-CoV, SARS-CoV, MERS-CoV and Bat-CoV).
Fig. 3
Fig. 3
Fellow diagram for COVID-19 confirmation.
Fig. 4
Fig. 4
After coronavirus infection, macrophages are activated and antigen-presenting cells (APC) display antigen to T cells. In cellular immunity, CD4 and CD8 with T cells produce cytokines to suppress the virus. T cells affect T helper cells to secrete interferons and interleukins. On the other hand, humoral immunity Th-2 activates B cells to produce memory B cells and antibodies. CoV attaches to DPP4R in the host cell through the S protein, causing genomic RNA to enter the cytoplasm. When CoV replicates, infected cell can partially start an immune response against dsRNA. The cascade of dsRNA and signaling pathways (IRF and NF-κB activation, respectively) sensitizes TLR-3 and is activated to produce type I IFN and proinflammatory cytokines. Type I IFN production plays a major role in increasing the release of antiviral proteins to protect uninfected cells.

References

    1. Agostini M.L. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio. 2018;9(2) p. e00221-18.
    1. Arabi Y.M. Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial. Trials. 2020;21(1):1–8.
    1. Badawi A., Ryoo S.G. Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. Int. J. Infect. Dis. 2016;49:129–133.
    1. Bassetti M., Vena A., Giacobbe D.R. The Novel Chinese Coronavirus (2019‐nCoV) Infections: challenges for fighting the storm. Eur. J. Clin. Invest. 2020;50(3)
    1. Bleibtreu A. Clinical management of respiratory syndrome in patients hospitalized for suspected Middle East respiratory syndrome coronavirus infection in the Paris area from 2013 to 2016. BMC Infect. Dis. 2018;18(1):331.
    1. Brown A.J. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antivir. Res. 2019;169:104541.
    1. Carlos W.G. Novel wuhan (2019-nCoV) coronavirus. Am. J. Respir. Crit. Care Med. 2020;201(4):P7–P8.
    1. Chan J.F.-W. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514–523.
    1. Chan J.F.-W. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microb. Infect. 2020;9(1):221–236.
    1. Channappanavar R. Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. J. Immunol. 2017;198(10):4046–4053.
    1. Chen Z.-M. Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus. World Journal of Pediatrics. 2020:1–7.
    1. Chen N. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
    1. Chu C. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59(3):252–256.
    1. Chu D.K. Molecular diagnosis of a novel coronavirus (2019-nCoV) causing an outbreak of pneumonia. Clin. Chem. 2020;66(4):549–555.
    1. Chung M. Radiology; 2020. CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV) p. 200230.
    1. Coleman C.M. Abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus fusion. J. Virol. 2016;90(19):8924–8933.
    1. Cui J., Li F., Shi Z.-L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 2019;17(3):181–192.
    1. De Clercq E. New nucleoside analogues for the treatment of hemorrhagic fever virus infections. Chemistry–An Asian Journal. 2019;14(22):3962–3968.
    1. de Wit E. SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol. 2016;14(8):523.
    1. Ding Y. The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function. BMC Compl. Alternative Med. 2017;17(1):130.
    1. Drosten C. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348(20):1967–1976.
    1. Dyall J. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob. Agents Chemother. 2014;58(8):4885–4893.
    1. Fahimi H. Dengue viruses and promising envelope protein domain III-based vaccines. Appl. Microbiol. Biotechnol. 2018;102(7):2977–2996.
    1. Forni D. Molecular evolution of human coronavirus genomes. Trends Microbiol. 2017;25(1):35–48.
    1. Fung T.S., Liu D.X. Human coronavirus: host-pathogen interaction. Annu. Rev. Microbiol. 2019;73:529–557.
    1. Gralinski L.E., Menachery V.D. Return of the coronavirus: 2019-nCoV. Viruses. 2020;12(2):135.
    1. Guan W.-j. MedRxiv; 2020. Clinical Characteristics of 2019 Novel Coronavirus Infection in China.
    1. Guo L. Clinical features predicting mortality risk in patients with viral pneumonia: the MuLBSTA score. Front. Microbiol. 2019;10:2752.
    1. Guo Y.-R. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Military Medical Research. 2020;7(1):1–10.
    1. Holshue M.L. First case of 2019 novel coronavirus in the United States. N. Engl. J. Med. 2020
    1. Huang C. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
    1. Huang P. Use of chest CT in combination with negative RT-PCR assay for the 2019 novel coronavirus but high clinical suspicion. Radiology. 2020;295(1):22–23.
    1. Hui D.S. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health—the latest 2019 novel coronavirus outbreak in Wuhan, China. Int. J. Infect. Dis. 2020;91:264–266.
    1. Ji W. Cross‐species transmission of the newly identified coronavirus 2019‐nCoV. J. Med. Virol. 2020;92(4):433–440.
    1. Ji S. Unique synergistic antiviral effects of Shufeng Jiedu Capsule and oseltamivir in influenza A viral-induced acute exacerbation of chronic obstructive pulmonary disease. Biomed. Pharmacother. 2020;121:109652.
    1. Jordan P.C. Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase. PLoS Pathog. 2018;14(2)
    1. Jung Y.J. bioRxiv; 2020. Comparative Analysis of Primer-Probe Sets for the Laboratory Confirmation of SARS-CoV-2.
    1. Kim J.-M. Identification of coronavirus isolated from a patient in Korea with COVID-19. Osong Public Health and Research Perspectives. 2020;11(1):3.
    1. Konermann S. Transcriptome engineering with RNA-targeting type VI-D CRISPR effectors. Cell. 2018;173(3):665–676. e14.
    1. Ksiazek T.G. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348(20):1953–1966.
    1. Lei J., Kusov Y., Hilgenfeld R. Nsp 3 of coronaviruses: structures and functions of a large multi-domain protein. Antivir. Res. 2018;149:58–74.
    1. Li F. Structure, function, and evolution of coronavirus spike proteins. Annual review of virology. 2016;3:237–261.
    1. Li G., De Clercq E. Nature Publishing Group; 2020. Therapeutic Options for the 2019 Novel Coronavirus (2019-nCoV)
    1. Li G. Coronavirus infections and immune responses. J. Med. Virol. 2020;92(4):424–432.
    1. Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV) Bioscience trends. 2020;14(1):69–71.
    1. Lucia C., Federico P.-B., Alejandra G.C. bioRxiv; 2020. An Ultrasensitive, Rapid, and Portable Coronavirus SARS-CoV-2 Sequence Detection Method Based on CRISPR-Cas12.
    1. Luk H.K. Molecular epidemiology, evolution and phylogeny of SARS coronavirus. Infect. Genet. Evol. 2019
    1. Metsky H.C. bioRxiv; 2020. CRISPR-based Surveillance for COVID-19 Using Genomically-Comprehensive Machine Learning Design.
    1. Momattin H., Al-Ali A.Y., Al-Tawfiq J.A. A systematic review of therapeutic agents for the treatment of the Middle East respiratory syndrome coronavirus (MERS-CoV) Trav. Med. Infect. Dis. 2019;30:9–18.
    1. Moxley G. Sexual dimorphism in innate immunity. Arthritis Rheum. 2002;46(1):250–258.
    1. Mulangu S. A randomized, controlled trial of Ebola virus disease therapeutics. N. Engl. J. Med. 2019;381(24):2293–2303.
    1. Nguyen T.M., Zhang Y., Pandolfi P.P. Nature Publishing Group; 2020. Virus against Virus: a Potential Treatment for 2019-nCov (SARS-CoV-2) and Other RNA Viruses.
    1. Organization W.H. World Health Organization (WHO); 2020. Pneumonia of Unknown Cause–China. Emergencies Preparedness, Response, Disease Outbreak News.
    1. Perlman S. Mass Medical Soc; 2020. Another Decade, Another Coronavirus.
    1. Phan T. Novel coronavirus: from discovery to clinical diagnostics. Infect. Genet. Evol. 2020;79
    1. Russell C.D., Millar J.E., Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020;395(10223):473–475.
    1. Sahin A.R. Novel coronavirus (COVID-19) outbreak: a review of the current literature. EJMO. 2019;4(1):1–7. 2020.
    1. Savarino A. New insights into the antiviral effects of chloroquine. Lancet Infect. Dis. 2006;6(2):67–69.
    1. Sheahan T.P. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med. 2017;9(396)
    1. Sheahan T.P. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun. 2020;11(1):1–14.
    1. Song Z. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 2019;11(1):59.
    1. Su S. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016;24(6):490–502.
    1. Sun J. COVID-19: epidemiology, evolution, and cross-disciplinary perspectives. Trends Mol. Med. 2020
    1. Sun X. medRxiv; 2020. The Infection Evidence of SARS-COV-2 in Ocular Surface: a Single-Center Cross-Sectional Study.
    1. Tang X. On the origin and continuing evolution of SARS-CoV-2. National Science Review. 2020
    1. van der Hoek L. Identification of a new human coronavirus. Nat. Med. 2004;10(4):368–373.
    1. Vincent M.J. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J. 2005;2(1):69.
    1. Wang Y. Comparative effectiveness of combined favipiravir and oseltamivir therapy versus oseltamivir monotherapy in critically ill patients with influenza virus infection. J. Infect. Dis. 2019
    1. Wang C. A novel coronavirus outbreak of global health concern. Lancet. 2020;395(10223):470–473.
    1. Wang D. Jama; 2020. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China.
    1. Wang M. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–271.
    1. Warren T.K. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016;531(7594):381–385.
    1. Weiss S.R., Leibowitz J.L. Advances in Virus Research. Elsevier; 2011. Coronavirus pathogenesis; pp. 85–164.
    1. Woo P.C. Coronavirus genomics and bioinformatics analysis. Viruses. 2010;2(8):1804–1820.
    1. Woo P.C. Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J. Virol. 2012;86(7):3995–4008.
    1. Wu C., Zheng M. 2020. Single-cell RNA Expression Profiling Shows that ACE2, the Putative Receptor of Wuhan 2019-nCoV, Has Significant Expression in the Nasal, Mouth, Lung and Colon Tissues, and Tends to Be Co-expressed with HLA-DRB1 in the Four Tissues.
    1. Xia S. A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike. Science advances. 2019;5(4):eaav4580.
    1. Xie X. Radiology; 2020. Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing; p. 200343.
    1. Yan Y. Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res. 2013;23(2):300–302.
    1. Yang X. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020
    1. Zaki A.M. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012;367(19):1814–1820.
    1. Zhou P. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020:1–4.
    1. Zhou W. Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia. Signal Transduction and Targeted Therapy. 2020;5(1):1–3.
    1. Zhu Z. Predicting the receptor-binding domain usage of the coronavirus based on kmer frequency on spike protein. Infect. Genet. Evol.: journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2018;61:183–184.
    1. Zhu N. A novel coronavirus from patients with pneumonia in China. N. Engl. J. Med. 2019 2020.
    1. Zumla A. Coronaviruses—drug discovery and therapeutic options. Nat. Rev. Drug Discov. 2016;15(5):327.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe