Interferon Pathways and Coronavirus Drug Targets

Interferon Pathways and Coronavirus Drug Targets

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Some plus-strand RNA viruses encode proteins with macrodomains (Kuri et al., 2011).
  • These domains have ADP-ribose-1?-phosphatase (ADRP) activity and/or bind poly (ADP-ribose), poly(A) or poly(G).
  • Macrodomain-related ADRP activities may be involved in viral escape from the innate immune responses.
  • Mutants of SARS-CoV and human coronavirus 229E (HCoV-229E) have been developed.
  • These mutants with ADRP-deficient macrodomains had higher sensitivity to the antiviral activities of interferon-? (Kuri et al., 2011).
  • In addition, the SARS-CoV could block interferon (IFN)-dependent signaling pathways.
  • The pathways are the primary steps of antiviral responses (Wathelet et al., 2007).
  • The SARS-CoV nonstructural protein 1 (nsp1) may be a virulence and pathogenic factor that supports viral replication.
  • Expression of nsp1 may block IFN-dependent signaling (Wathelet et al., 2007).
  • The viral protein nsp1 may be a potential antiviral drug target.

References:

Kuri, T., Eriksson, K. K., Putics, A., Z

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The Spike Protein, ACE2, and Coronaviruses

The Spike Protein, ACE2, and Coronaviruses

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • It is important to understand the SARS-CoV genome, evolution and lifecycle.
  • The spike (S) protein of the SARS-CoV is essential in viral entry into host cells (Simmons et al., 2013).
  • Host cell proteases cleave and activate the spike (S) protein of the SARS-CoV.
  • Cathepsins and type II transmembrane serine proteases are crucial cellular activators of SARS-CoV for viral infectivity.
  • Emerging coronaviruses may use these enzymes to enhance their spread (Simmons et al., 2013).
  • This is done through interacting with cellular receptors for membrane fusion (Keng et al., 2005).
  • This mechanism can be the major target of neutralizing antibodies and important for the development of vaccines.
  • Antibodies may recognize the mature form of the S protein on the cell surface (Keng et al., 2005).
  • The anti-SDelta10 antibody targeting the S amino acid residues with heptad repeat 2 may have neutralizing effects.
  • The S region with neutralizing epitopes is critical for the virus entry into cells, and may be drug/vaccine targets (Keng et al., 2005).
  • In addition, the angiotensin-converting enzyme 2 (ACE2) is a receptor for the SARS-CoV entry process (Kuhn et al., 2007).
  • In summary, two potential drug targets are the SARS-CoV spike protein and ACE2.
  • Potential drugs can be developed against these targets to block SARS-CoV replication and cellular entry (Kuhn et al., 2007).

References:

Keng, C.-T., Zhang, A., Shen, S., Lip, K.-M., Fielding, B. C., Tan, T. H. P., Chou, C.-F., Loh, C. B., Wang, S., Fu, J., Yang, X., Lim, S. G., Hong, W., & Tan, Y.-J. (2005). Amino acids 1055 to 1192 in the S2 region of severe acute respiratory syndrome coronavirus S protein induce neutralizing antibodies: Implications for the development of vaccines and antiviral agents. Journal of Virology, 79(6), 3289

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Host Factors and Antiviral Targets


Host Factors and Antiviral Targets

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Host factors associated with SARS-CoV replication need to be investigated (de Wilde et al., 2015).
  • These factors include the innate immune response and the metabolism of complex lipids that are involved in SARS-CoV infection.
  • The early secretory pathways are essential for SARS-CoV replication.
  • Protein kinases are crucial regulators of cellular functions.
  • The knockdown of protein kinases may reveal factors and pathways associated with virus replication.
  • Depletion of the antiviral double-stranded RNA-activated protein kinase (PKR) promoted virus replication.
  • Cyclin-dependent kinase 6 (CDK6) has been found as an antiviral host factor in SARS-CoV replication (de Wilde et al., 2015).
  • The pro- and antiviral host factors and pathways of viral replication are important for finding drug targets.

References:

de Wilde, A. H., Wannee, K. F., Scholte, F. E. M., Goeman, J. J., Ten Dijke, P., Snijder, E. J., Kikkert, M., & van Hemert, M. J. (2015). A Kinome-Wide Small Interfering RNA Screen Identifies Proviral and Antiviral Host Factors in Severe Acute Respiratory Syndrome Coronavirus Replication, Including Double-Stranded RNA-Activated Protein Kinase and Early Secretory Pathway Proteins. Journal of Virology, 89(16), 8318

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Saikosaponins and Coronaviruses

Saikosaponins

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Saikosaponins are oleanane derivatives including glucosides (Cheng et al., 2006).
  • Saikosaponins are extracted from plants such as Bupleurum spp., Heteromorpha spp. and Scrophularia scorodonia.
  • Saikosaponins have anti-inflammatory activities with anti-hepatitis, anti-nephritis, and antihepatoma effects.
  • They may also have immunomodulation and antibacterial functions.
  • The potential anti-coronaviral effects of saikosaponins (A, B2, C and D) have been tested.
  • The saikosaponins A and B2 showed no cytotoxic effects on target cells.
  • Saikosaponin B2 had the strongest suppressing effects on viral attachment and penetration (Cheng et al., 2006).
  • Saikosaponin B2 may have anti-coronaviral effects in the early stage of viral replication.

References:

Cheng, P.-W., Ng, L.-T., Chiang, L.-C., & Lin, C.-C. (2006). Antiviral effects of saikosaponins on human coronavirus 229E in vitro. Clinical and Experimental Pharmacology & Physiology, 33(7), 612

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Antiviral Compounds and Human Coronavirus OC43

Antiviral Compounds and Human Coronavirus OC43

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Stephania tetrandra and Menispermaceae contain the bis-benzylisoquinoline alkaloids tetrandrine (TET) (Kim et al., 2019).
  • They also have fangchinoline (FAN) and cepharanthine (CEP).
  • These compounds have anticancer and anti-inflammatory effects.
  • They may also have antiviral activities against human coronaviruses.
  • The antiviral activities of TET, FAN, and CEP were examined in HCoV-OC43-infected human lung cells.
  • These compounds suppressed virus-caused cell death during the early stages of viral infection.
  • TET, FAN, and CEP treatment inhibited the viral replication, and viral S and N protein expressions (Kim et al., 2019).
  • TET, FAN, and CEP may be potential natural antiviral products for the prevention and therapy of HCoV-OC43 infections.

References:

Kim, D. E., Min, J. S., Jang, M. S., Lee, J. Y., Shin, Y. S., Song, J. H., Kim, H. R., Kim, S., Jin, Y.-H., & Kwon, S. (2019). Natural Bis-Benzylisoquinoline Alkaloids-Tetrandrine, Fangchinoline, and Cepharanthine, Inhibit Human Coronavirus OC43 Infection of MRC-5 Human Lung Cells. Biomolecules, 9(11).

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Herbal Extracts May Inhibit Coronavirus Replication

Herbal Extracts May Inhibit Coronavirus Replication

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Medicinal herbal extracts have been screened for their antiviral effects on coronavirus replication (Kim et al., 2008; Kim et al., 2010).
  • The extracts may suppress the replication of mouse hepatitis virus A59 (MHV-A59) and the intracellular RNA and protein expression.
  • They may also suppress porcine epidemic diarrhea virus (PEDV) (Kim et al., 2008).
  • These herbs include Cimicifuga rhizoma, Meliae cortex, Coptidis rhizoma, Phellodendron cortex and Sophora subprostrata radix.
  • These extracts may reduce PEDV and vesicular stomatitis virus (VSV) production (Kim et al., 2008).
  • The herbal extracts may suppress MHV replication and may become candidates for anti-coronavirus therapeutics.
  • Acanthopanacis cortex and Torilis fructus may decrease intracellular viral RNA levels and inhibit viral proteins (Kim et al., 2010).  
  • The extracts may inhibit the replication of the John Howard Mueller strain of MHV and vesicular stomatitis virus.
  • Sanguisorbae radix may inhibit coronavirus production and protein synthesis.
  • Acanthopanacis cortex and Torilis fructus may promote cyclooxygenase-2 expression.
  • They may activate extracellular signal-related kinase (ERK) and p38 or ERK alone, respectively.
  • Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix and Torilis fructus may have anti-coronavirus effects (Kim et al., 2010).

References:

Kim, H.-Y., Eo, E.-Y., Park, H., Kim, Y.-C., Park, S., Shin, H.-J., & Kim, K. (2010). Medicinal herbal extracts of Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix and Torilis fructus inhibit coronavirus replication in vitro. Antiviral Therapy, 15(5), 697

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Antiviral Flavonoids from Houttuynia Cordata

Antiviral Flavonoids from Houttuynia Cordata

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • The ethyl acetate (EA) fraction of Houttuynia cordata (H. cordata) Thunb. (Saururaceae) may have antiviral effects.
  • It may be used against coronaviruses and dengue virus (DENV) (Chiow et al., 2016).
  • H. cordata has flavonoids including quercetin, quercitrin and rutin.
  • The antiviral effects of H. cordata and flavonoids were tested against mouse hepatitis virus (MHV) and DENV type 2 (DENV-2).
  • The EA fraction of H. cordata suppressed viral infectivity up to 6 days.
  • The EA fraction did not cause acute toxicity in mice.
  • Some flavonoids showed weak antiviral effects, e.g., quercetin suppressed both MHV and DENV-2 (Chiow et al., 2016).
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Sabadinine, Houttuynia Cordata, and Coronaviruses

Sabadinine and Houttuynia Cordata

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • The replication of CoVs relies on proteolytic processing (Toney et al., 2004).
  • The major proteinase, 3C-like protease (3CLpro), may become a target for anti-SARS drugs.
  • A study used molecular docking into the active site of 3CLpro, looking for non-peptidyl inhibitors (Toney et al., 2004).
  • A potential antiviral compound was found to be sabadinine extracted from a natural herb (Toney et al., 2004).
  • Moreover, Houttuynia cordata Thunb. (Saururaceae)(HC) is an herb that has been used to treat pneumonia (Lau et al., 2008).
  • HC water extract enhanced the proportions of CD4(+) and CD8(+) T cells.
  • It may promote the production of IL-2 and IL-10 by mouse splenic lymphocytes (Lau et al., 2008).
  • HC may also inhibit 3CLpro and RNA-dependent RNA polymerase (RdRp) of SARS-CoV.
  • Oral acute toxicity tests showed that HC was non-toxic for oral administration (Lau et al., 2008).
  • HC extracts may be useful for the development of antiviral agents for SARS.

References:

Lau, K.-M., Lee, K.-M., Koon, C.-M., Cheung, C. S.-F., Lau, C.-P., Ho, H.-M., Lee, M. Y.-H., Au, S. W.-N., Cheng, C. H.-K., Lau, C. B.-S., Tsui, S. K.-W., Wan, D. C.-C., Waye, M. M.-Y., Wong, K.-B., Wong, C.-K., Lam, C. W.-K., Leung, P.-C., & Fung, K.-P. (2008). Immunomodulatory and anti-SARS activities of Houttuynia cordata. Journal of Ethnopharmacology, 118(1), 79

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Glycyrrhizin, Cinnamomi Cortex, and Toona Sinensis Roem

Glycyrrhizin, Cinnamomi Cortex, and Toona Sinensis Roem

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Glycyrrhizin (GL) may suppress SARS-CoV replication (Hoever et al., 2005).
  • The insertion of 2-acetamido-beta-d-glucopyranosylamine into the GL glycoside chain increased the antiviral effects to 10-fold higher.
  • Amides and conjugates of GL with two amino acid residues and a free 30-COOH function increased the effects up to 70-fold higher.
  • However, they caused higher cytotoxicity with lower selectivity index (Hoever et al., 2005).
  • In addition, the butanol fraction of Cinnamomi Cortex (CC/Fr.2) may suppress SARS-CoV (Zhuang et al., 2009).
  • It may also inhibit HIV/SARS-CoV S pseudovirus infections.
  • The compounds from CC such as procyanidin A2 and procyanidin B1 may have moderate antiviral effects (Zhuang et al., 2009).
  • CC/Fr.2 could block the clathrin-dependent endocytosis pathway and suppress the internalization of transferrin receptor.
  • CC/Fr.2 may have the antiviral activities for SARS-CoV by blocking endocytosis (Zhuang et al., 2009).
  • Moreover, TSL-1, the extract from Toona sinensis Roem (Cedrela sinensis; TSR), may also inhibit SARS-CoV (Chen et al., 2008).

References:

Chen, C.-J., Michaelis, M., Hsu, H.-K., Tsai, C.-C., Yang, K. D., Wu, Y.-C., Cinatl, J., & Doerr, H. W. (2008). Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication. Journal of Ethnopharmacology, 120(1), 108

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The Antiviral Flavonoids for SARS-CoV and HCV

The Antiviral Flavonoids for SARS-CoV and HCV

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Aryl diketoacid (ADK) has antiviral effects that can be improved by adding an aromatic arylmethyl substituent (Park et al., 2012).
  • A natural flavonoid quercetin has a 3,5-dihydroxychromone pharmacophore.
  • It is in association with the 1,3-diketoacid moiety of the ADK (Park et al., 2012).
  • It is necessary to examine the antiviral effects of the quercetin derivatives with an arylmethyl group attached.
  • Some 7-O-arylmethylquercetin derivatives with aromatic substituents were assessed for their antiviral effects (Park et al., 2012).
  • The effects were examined against the SARS-CoV and hepatitis C virus (HCV).
  • Aromatic substituents improved the effects of the 7-O-arylmethylquercetin derivatives against SCV and HCV (Park et al., 2012).

References:

Park, H. R., Yoon, H., Kim, M. K., Lee, S. D., & Chong, Y. (2012). Synthesis and antiviral evaluation of 7-O-arylmethylquercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV). Archives of Pharmacal Research, 35(1), 77

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Emodin and the SARS Coronavirus

Emodin and the SARS Coronavirus

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • SARS-CoV spike (S) protein is a type I membrane-bound protein (Ho et al., 2007).
  • It has an elemental role for the viral attachment to the host cell receptor angiotensin-converting enzyme 2 (ACE2).
  • The screening of 312 medicinal herbs found three herbs of the family Polygonaceae with potential antiviral effects (Ho et al., 2007).
  • The herbs suppressed the interactions between the S protein and ACE2.
  • The three herbs were:
    • Radix et Rhizoma Rhei (the root tubers of Rheum officinale Baill.);
    • Radix Polygoni multiflori (the root tubers of Polygonum multiflorum Thunb.);
    • Caulis Polygoni multiflori (the vines of P. multiflorum Thunb.).
  • Emodin is an anthraquinone compound extracted from genus Rheum and Polygonum.
  • Emodin inhibited the S protein and ACE2 interaction in a dose-dependent way.
  • It also suppressed the infectivity of S protein-pseudotyped retrovirus.
  • Emodin may become a potential antiviral agent for the therapy of SARS (Ho et al., 2007).

References:

Ho, T.-Y., Wu, S.-L., Chen, J.-C., Li, C.-C., & Hsiang, C.-Y. (2007). Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Research, 74(2), 92

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Antiviral Herbal Compounds for SARS-CoV Ion Channels

Antiviral Herbal Compounds for SARS-CoV Ion Channels

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • The protein coded by the open-reading-frame 3a of SARS coronavirus may form a cation-selective channel (Schwarz et al., 2014).
  • The channel is important in virus release.
  • Drugs that suppress the ion channel may suppress virus release.
  • Many herbal products with anticancer effects may also have antiviral activities.
  • Such herbal products include the flavonols kaempferol, kaempferol glycosides, and acylated kaempferol glucoside derivatives.
  • These herbal products may block the 3a channel.
  • The most effective one may be the glycoside juglanin (with an arabinose residue) for blocking the 3a-mediated current.
  • Kaempferol derivatives with rhamnose residue may also have antiviral effects (Schwarz et al., 2014).
  • Coronaviral ion channels can be antiviral drug targets, e.g., the 3a channel proteins may be inhibited by kaempferol glycosides.

References:

Schwarz, S., Sauter, D., Wang, K., Zhang, R., Sun, B., Karioti, A., Bilia, A. R., Efferth, T., & Schwarz, W. (2014). Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus. Planta Medica, 80(2

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The Antiviral Compound for MERS-CoV

The Antiviral Compound for MERS-CoV

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • A type of nucleoside analogues may be similar to the natural nucleosides that can block viral replication (Agostini et al., 2019).
  • Potent antiviral effects of a broad-spectrum ribonucleoside analogue, ?-d-N4-hydroxycytidine (NHC) have been identified.
  • Studies found that viral proofreading activity did not influence the sensitivity to NHC inhibition (Agostini et al., 2019).
  • The finding refers to the interaction between a nucleoside analogue inhibitor and the CoV replicase.
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Structural Analysis for Antiviral Compounds

Structural Analysis for Antiviral Compounds

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • The coronavirus main protease (M(pro)) is critical in viral gene expression (Xue et al., 2008).
  • The viral replication through the proteolytic processing of replicase polyproteins may be a potential antiviral target.
  • The crystal structures of infectious bronchitis virus (IBV) M(pro) and SARS-CoV M(pro) mutant (H41A) are important.
  • The structures of the N-terminal autocleavage substrate are also critical.
  • These structures can be used to describe the structural flexibility and substrate binding of M(pro).
  • A monomeric form of IBV M(pro) was identified in CoV M(pro) structures.
  • A comparison of these M(pro) structures may be helpful for the design of substrate-based inhibitors targeting CoV M(pro)s.
  • A Michael acceptor inhibitor (N3) was co-crystallized with IBV M(pro) and led to inactivation of IBV M(pro).
  • The structure-based optimization of N3 has led to compounds N27 and H16 that may inhibit SARS-CoV M(pro) (Xue et al., 2008).

A Potential Antiviral Molecule for SARS-CoV and Ebola

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • SARS-CoV and Ebola, Hendra, and Nipah viruses belong to different viral families.
  • These viruses need cathepsin L for entering their target cells (Elshabrawy et al., 2014).
  • The viral glycoproteins are primed by protease cleavage before fusing with the host cell membrane (Elshabrawy et al., 2014).
  • A high-throughput assay has been used to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins.
  • A broad-spectrum small molecule was able to inhibit the cathepsin L-mediated cleavage and the entry of glycoprotein pseudotypes.
  • The small molecule may be a candidate as a broad-spectrum antiviral drug against these viruses (Elshabrawy et al., 2014).

References:

Elshabrawy, H. A., Fan, J., Haddad, C. S., Ratia, K., Broder, C. C., Caffrey, M., & Prabhakar, B. S. (2014). Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay. Journal of Virology, 88(8), 4353

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Potential Antiviral Compounds for Coronaviruses: Tests and Screenings

Potential Antiviral Compounds for Coronaviruses: Tests and Screenings

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Some agents inhibiting coronaviral replication have been investigated (Golda and Pyrc, 2008).
  • The potential antiviral agents include (Golda and Pyrc, 2008):
    • Carbohydrate-binding agents;
    • Neutralizing antibodies;
    • Drugs targeting the coronaviral envelope protein.
  • Real-time PCR has been used for testing antivirals against Lassa virus, SARS coronavirus, and Ebola virus (G
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Antiviral Antibodies, Immunity, and Coronaviruses

Antiviral Antibodies and Coronaviruses

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Mutations in virus-derived CD8 T-cell epitopes may abolish cytotoxic T-lymphocyte (CTL) recognition (Butler et al., 2007).
  • The mutations may block virus clearance in coronavirus-infected hosts.
  • These
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Potential Antiviral Agents for SARS and Various Coronaviruses

Indomethacin for Various Coronaviruses

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Cyclopentenone cyclooxygenase (COX) metabolites have been found to be useful targets against RNA viruses (Amici et al., 2006).
  • The COX inhibitor indomethacin (INDO) may have antiviral effects against SARS-CoV and canine coronavirus (CCoV).
  • INDO may inhibit the viral RNA synthesis and replication.
  • The antiviral effects of INDO have been tested in CCoV-infected dogs (Amici et al., 2006).
  • INDO has both anti-inflammatory and antiviral effects with potentials for the treatment of SARS and other coronaviruses.

P-PMOs for Murine Hepatitis Virus (MHV)

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • The antiviral effects of peptide-conjugated antisense phosphorodiamidate morpholino oligomers (P-PMOs) were examined.
  • P-PMOs were tested for several strains of murine hepatitis virus (MHV) (Burrer et al., 2007).
  • One of the P-PMOs (5TERM) complementary to the 5
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Remdesivir and Chloroquine as Potential Broad-Spectrum Antiviral Drugs

Remdesivir As A Potential Broad-Spectrum Antiviral Drug

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • The nucleoside analogue GS-5734 (remdesivir) has been found to inhibit human and zoonotic CoVs (Agostini et al., 2018).
  • GS-5734 may inhibit murine hepatitis virus (MHV), SARS-CoV and MERS-CoV.
  • GS-5734 could be a broad-spectrum drug to protect against current and novel CoVs.
  • The effects of nucleoside-based therapeutics may be blocked by a proofreading exoribonuclease (ExoN), e.g., the CoV nsp14 ExoN.
  • To solve the problem, a group ?-2a CoV was added to the nucleotide prodrug remdesivir (GS-5734).
  • Higher and nontoxic concentrations of GS-5734 may help overcome the viral resistance.
  • Further development of GS-5734 has the potential to make it as an effective pan-CoV antiviral agent (Agostini et al., 2018).        

The Broad-Spectrum Antiviral Effects of Chloroquine

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • HCoVs including HCoV-OC43 may cause 15 to 30% of mild upper respiratory tract infections (Keyaerts et al., 2009).
  • Chloroquine has been used for its antimalarial functions, and may inhibit HCoV-OC43 replication.
  • Chloroquine may also prevent HCoV-OC43-induced death in newborn mice given through maternal milk.
  • The high survival rate occurred when the mother mice were given the drug with 15 mg/kg of body weight/day.
  • Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg and 13% survival with 1 mg/kg.
  • Chloroquine has been found effective against HCoV-OC43 infection in mice as a potential drug (Keyaerts et al., 2009).

References:

Agostini, M. L., Andres, E. L., Sims, A. C., Graham, R. L., Sheahan, T. P., Lu, X., Smith, E. C., Case, J. B., Feng, J. Y., Jordan, R., Ray, A. S., Cihlar, T., Siegel, D., Mackman, R. L., Clarke, M. O., Baric, R. S., & Denison, M. R. (2018). Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. MBio, 9(2). https://doi.org/10.1128/mBio.00221-18

Keyaerts, E., Li, S., Vijgen, L., Rysman, E., Verbeeck, J., Van Ranst, M., & Maes, P. (2009). Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrobial Agents and Chemotherapy, 53(8), 3416

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Broad-Spectrum Antiviral Drugs for Coronaviruses

Broad-Spectrum Antiviral Drugs for Coronaviruses

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • Broad-spectrum antiviral drugs may lower the vulnerability of public health systems to the coronavirus pandemic.
  • Broad-spectrum antiviral drugs are needed to
    • Combat the emergence of novel coronaviruses, e.g., COVID-19;
    • Prevent the re-emergence of SARS-CoV, its mutants, and other related viruses;
    • Combat the continuance of MERS-CoV infections (Totura and Bavari, 2019).
  • Experiences from SARS and MERS outbreaks have revealed the demands for drugs with pan-coronavirus antiviral activities.

Antiviral Strategies for Coronaviruses

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • Nucleoside analogues may have antiviral effects against SARS-CoV (Chu et al., 2006).
  • Methods can be developed to antagonize viral nonstructural proteins (Totura and Bavari, 2019).
  • Agents can be designed to neutralize structural proteins of the coronaviruses.
  • Approaches can be developed to modulate essential host elements of viral infections.

References:

Chu, C. K., Gadthula, S., Chen, X., Choo, H., Olgen, S., Barnard, D. L., & Sidwell, R. W. (2006). Antiviral activity of nucleoside analogues against SARS-coronavirus (SARS-coV). Antiviral Chemistry & Chemotherapy, 17(5), 285

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About Coronaviruses (CoVs)

About Coronaviruses (CoVs) (From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • Coronaviruses (CoVs) may lead to lethal infections, but currently no effective antiviral therapeutics or vaccines are available.
  • The pandemic of the deadly coronavirus disease 2019 (COVID-19) is a reminder that such coronaviruses can emerge at any time.
  • COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • Novel human coronaviruses (HCoVs) may lead to severe respiratory tract infections such as bronchiolitis and pneumonia.
  • More than 15 years have passed since the severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from China.
  • SARS is an acute respiratory disease with high morbidity and mortality.
  • The Middle East respiratory syndrome coronavirus (MERS-CoV) is another fatal zoonotic virus (Totura and Bavari, 2019).
  • These coronaviruses can cause Acute Respiratory Distress Syndrome (ARDS) and renal failure.
  • They are highly transmissible and can spread from person-to-person through close contact (Totura and Bavari, 2019).

References:

Totura, A. L., & Bavari, S. (2019). Broad-spectrum coronavirus antiviral drug discovery. Expert Opinion on Drug Discovery, 14(4), 397

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Studies about Antiviral Drugs for Coronaviruses


The Antiviral Remdesivir and the Coronavirus SARS-CoV

Agostini, M. L., Andres, E. L., Sims, A. C., Graham, R. L., Sheahan, T. P., Lu, X., Smith, E. C., Case, J. B., Feng, J. Y., Jordan, R., Ray, A. S., Cihlar, T., Siegel, D., Mackman, R. L., Clarke, M. O., Baric, R. S., & Denison, M. R. (2018). Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. MBio, 9(2). https://doi.org/10.1128/mBio.00221-18

The Antiviral Compound ?-d-N4-Hydroxycytidine and the Coronavirus MERS-CoV

Agostini, M. L., Pruijssers, A. J., Chappell, J. D., Gribble, J., Lu, X., Andres, E. L., Bluemling, G. R., Lockwood, M. A., Sheahan, T. P., Sims, A. C., Natchus, M. G., Saindane, M., Kolykhalov, A. A., Painter, G. R., Baric, R. S., & Denison, M. R. (2019). Small-Molecule Antiviral ?-d-N4-Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance. Journal of Virology, 93(24). https://doi.org/10.1128/JVI.01348-19

The Antiviral Indomethacin and the Coronavirus SARS-CoV

Amici, C., Di Caro, A., Ciucci, A., Chiappa, L., Castilletti, C., Martella, V., Decaro, N., Buonavoglia, C., Capobianchi, M. R., & Santoro, M. G. (2006). Indomethacin has a potent antiviral activity against SARS coronavirus. Antiviral Therapy, 11(8), 1021

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Resources for Studying the 2019-nCoV Coronavirus (COVID-19): Databases and Tools

Resources for Studying the 2019-nCoV Coronavirus (COVID-19): Databases and Tools

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Metabolomics of Obesity: Gut Microbiota

Recent Development in Metabolomics of Obesity: Gut Microbiota and Metabolic Syndrome

Abu Bakar, M. H., Sarmidi, M. R., Cheng, K.-K., Ali Khan, A., Suan, C. L., Zaman Huri, H., & Yaakob, H. (2015). Metabolomics – the complementary field in systems biology: A review on obesity and type 2 diabetes. Molecular BioSystems, 11(7), 1742

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Biomarkers Database: Obesity in Different Populations

Park, B.-Y., Hong, J., & Park, H. (2017). Neuroimaging biomarkers to associate obesity and negative emotions. Scientific Reports, 7(1), 7664. https://doi.org/10.1038/s41598-017-08272-8

Pecht, T., Gutman-Tirosh, A., Bashan, N., & Rudich, A. (2014). Peripheral blood leucocyte subclasses as potential biomarkers of adipose tissue inflammation and obesity subphenotypes in humans. Obesity Reviews: An Official Journal of the International Association for the Study of Obesity, 15(4), 322

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Biomarkers Database: Obesity, Cognition, and Inflammation

Garcia-Mazcorro, J. F., Mills, D. A., Murphy, K., & Noratto, G. (2018). Effect of barley supplementation on the fecal microbiota, caecal biochemistry, and key biomarkers of obesity and inflammation in obese db/db mice. European Journal of Nutrition, 57(7), 2513

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