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Review
. 2021 Jan;26(1):229-239.
doi: 10.1016/j.drudis.2020.10.018. Epub 2020 Oct 27.

Union is strength: antiviral and anti-inflammatory drugs for COVID-19

Jose J Naveja  1 , Abraham Madariaga-Mazón  1 , Francisco Flores-Murrieta  2 , Julio Granados-Montiel  3 , Marco Maradiaga-Ceceña  4 , Víctor Duarte Alaniz  1 , Maricruz Maldonado-Rodriguez  5 , Jazmín García-Morales  5 , Juan Pablo Senosiain-Peláez  5 , Karina Martinez-Mayorga  6
Affiliations
Review

Union is strength: antiviral and anti-inflammatory drugs for COVID-19

Jose J Naveja et al. Drug Discov Today. 2021 Jan.
No abstract available

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Figures

None
Graphical abstract
Fig. 1
Fig. 1
General overview of potentially therapeutic viral and human targets involved in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The viral capsid contains a single-stranded RNA genome that encodes different structural proteins, such as the spike protein [blue ribbons and surfaces; Protein Data Bank (PDB) ID 6m17]; and nonstructural proteins (nsp), including the main protease (green ribbons and surface; PDB ID 6lu7) and the mega-complex formed by the RNA-dependent RNA-polymerase (Rdrp; orange ribbons and surface; PDB ID 7bv2) with its co-factors NSP7 and NSP8 (yellow ribbons and surface) and the exonuclease formed by NSP10 and NSP14 (magenta ribbons and surface, model created by homology modeling). Some of the host targets relevant in SARS-CoV-2 infection are the furin protease (light-red ribbons and surface, PDB ID 5mim), the transmembrane protease TMPRSS2 (pink membrane, model created by homology modeling), and angiotensin-converting enzyme 2 (ACE2; light-green ribbons and surface, PDB ID 6m17), which binds to the viral spike protein.
Fig. 2
Fig. 2
Common interactions in ligands co-crystallized with Mpro. (a) Protein–ligand interaction fingerprint (PLIF) for ligands K36 [Protein Data Bank (PDB) ID 6WTT], U5G (PDB ID 6M0K), P6N (PDB ID 6YNQ), O6K (PDB ID 6Y2F), UED (PDB ID 6WTK), PK8 (PDB ID 6YT8), NOL (PDB ID 7C8T), X77 (PDB ID 6W63), 3 W L (PDB ID 6M2N), TG3 (PDB ID 7C8R), and N3 (PDB ID 6LU7) by percentage frequency. (b) Superposition of Mpro co-crystallized ligands (orange stick and ball represent the ligand N3, orange lines represent the other ligands) and amino acids of interaction within the active site of the Mpro (gray ribbons, white ball and stick).
Fig. 3
Fig. 3
Results from a factor analyses for the integration of ICM docking against Mpro, RNA-dependent RNA-polymerase (RdRp), and spike protein. (a) Configuration loadings for factor 1 and factor 2 are represented as vectors. Although a third factor was extracted in this case, it lies orthogonal to the plane and is not represented. (b) Molecules screened are mapped into the space defined by factor 1 and factor 2; red dots represent molecules with registered clinical trials against Coronavirus 2019 (COVID-19), and green rectangles outline the consensus subset of molecules. See Tables S4 and S6 in the supplemental information online for more details on factor loads and consensus thresholds, respectively.
Fig. 4
Fig. 4
Docking models for lymecycline (blue sticks) into (a) Mpro; (b) spike protein; (c) furin; (d) RNA-dependent RNA-polymerase (RdRp); and (a) for famotidine (orangesticks) into Mpro.
See this image and copyright information in PMC

References

    1. Chen Y. Emerging coronaviruses: genome structure, replication, and pathogenesis. J. Med. Virol. 2020;92:418–423. - PMC - PubMed
    1. Baud D. Real estimates of mortality following COVID-19 infection. Lancet Infect. Dis. 2020;20:773. - PMC - PubMed
    1. Liu Y. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J. Travel Med. 2020;27(2):1–4. - PMC - PubMed
    1. Rodriguez-Morales A.J. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med. Infect. Dis. 2020;34:101623. - PMC - PubMed
    1. Bai Y. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020;323:1406–1407. - PMC - PubMed

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