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Review
. 2020 Dec;81(8):942-949.
doi: 10.1002/ddr.21710. Epub 2020 Jul 13.

Therapeutic dilemma in the repression of severe acute respiratory syndrome coronavirus-2 proteome

Aatika Sadia  1 , Muhammad Asim Raza Basra  1
Affiliations
Review

Therapeutic dilemma in the repression of severe acute respiratory syndrome coronavirus-2 proteome

Aatika Sadia et al. Drug Dev Res. 2020 Dec.

Abstract

Currently, the pandemic coronavirus disease 2019 (COVID-19) has unprecedentedly captivated its human hosts by causing respiratory illnesses because of evolution of the genetic makeup of novel coronavirus (CoV) known as severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). As much as the researchers are inundated for the quest of effective treatments from available drugs, the discovery and trials of new experimental drugs are also at a threshold for clinical trials. There has been much concern regarding the new and targeted drugs considering the comprehensive ambiguity regarding the mechanism and pathway of the drug action with respect to the new and unpredictable structural and nonstructural proteins (NSPs) of SARS CoV-2. This study was aimed to discuss functional pathways related to NSPs in CoVs with updated knowledge regarding SARS CoV-2, mechanisms of action of certain approved and investigational drugs for correct orientation regarding the treatment strategies, including nucleotide analog mechanism, receptor analog mechanism, and peptide-peptide interactions, along with the impact of COVID-19 on a global scale. Although there is a dire need for targeted drugs against SARS CoV-2, the practical achievement of its cure is possible by only using effective drugs with appropriate mechanisms to eliminate the disease.

Keywords: COVID-19; SARS CoV-2; antiviral drugs; cytokines; nonstructural proteins; pneumonia; severe acute respiratory syndrome; viremia.

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Conflict of interest statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.

Figures

FIGURE 1
FIGURE 1
Phylogenetic family tree of coronaviruses infecting human hosts
FIGURE 2
FIGURE 2
Infection and cytokine storm pathway of COVID‐19 in host alveolar cell. 3CLPro, 3‐Cysteine‐like protease; ACE‐2, angiotensin converting enzyme‐2; APS, autophagosome; ExoN, exonuclease; H.S.P, host signaling protein; MTase, methyl transferase; NSP, nonstructural protein; PLPro, papain‐like protease; RTC, restriction‐transcription complex
FIGURE 3
FIGURE 3
Schematic diagram of mechanisms of inhibition. (a) RNA‐dependent RNA polymerase (RDRP‐NSP12) along with NSP7 and NSP8 cofactors replicate viral RNA using incoming nucleoside triphosphates (NTPs) and nucleoside analog triphosphates (NATPs), while the proofreader NSP14 exonuclease detects and excises nucleotide analogs and the RDRP replaces them with corresponding nucleosides (N). (b) Translation of viral RNA into protein inhibited be receptor analog (RA) drugs or peptide inhibitor (p)
See this image and copyright information in PMC

References

    1. Ahmadpoor, P. , & Rostaing, L. (2020). (n.d.). Why the immune system fails to mount an adaptive immune response to a COVID‐19 infection. Transplant International, 33, 824–825. 10.1111/tri.13611 - DOI - PubMed
    1. Alsaadi, E. A. J. , & Jones, I. M. (2019). Membrane binding proteins of coronaviruses. Future Virology, 14(4), 275–286. 10.2217/fvl-2018-0144 - DOI - PMC - PubMed
    1. Angeletti, S. , Benvenuto, D. , Bianchi, M. , Giovanetti, M. , Pascarella, S. , & Ciccozzi, M. (2020). COVID‐2019: The role of the nsp2 and nsp3 in its pathogenesis. Journal of Medical Virology, 92(6), 584–588. 10.1002/jmv.25719 - DOI - PMC - PubMed
    1. Arabi, Y. M. , Asiri, A. Y. , Assiri, A. M. , Jokhdar, H. A. A. , Alothman, A. , Balkhy, H. H. , … Al Jeraisy, M. (2020). 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, 21(1), 1–8. - PMC - PubMed
    1. Cao, Y.‐C. , Deng, Q.‐X. , & Dai, S.‐X. (2020). Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID‐19: An evaluation of the evidence. Travel Medicine and Infectious Disease, 101647, 35, 101647. 10.1016/j.tmaid.2020.101647 - DOI - PMC - PubMed

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