Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease

Zhang, M.; Wang, Y.; He, Wentian; Sun, Yuna; Guo, Yu; Zhong, Weiming; Gao, Qiang; Liao, Maofu; Wang, X.; Cai, Yan; Rao, Zihe

doi:10.1021/acs.jmedchem.9b01414

Cited by 14 publications

(16 citation statements)

References 36 publications

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“…For review of capsid inhibitors targeting enteroviruses in general, please refer to recent reviews. , A number of capsid inhibitors have been reported to inhibit EV-A71, CVB3, or poliovirus in either in vitro cell culture model or in vivo mouse model studies. − However, their antiviral activity has not been evaluated against EV-D68.…”

Section: Capsid Inhibitors (Vp1–vp4)mentioning

confidence: 99%

Enterovirus D68 Antivirals: Past, Present, and Future

Musharrafieh

Zheng

et al. 2020

ACS Infect. Dis.

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Enterovirus D68 (EV-D68) is an RNA virus that causes respiratory illnesses mainly in children. In severe cases, it can lead to neurological complications such as acute flaccid myelitis (AFM). EV-D68 belongs to the enterovirus genera of the Picornaviridae family, which also includes many other significant human pathogens such as poliovirus, enterovirus A71, and rhinovirus. There are currently no vaccines or antivirals against EV-D68. In this review, we present the current understanding of the link between EV-D68 and AFM, the mechanism of viral replication, and recent progress in developing EV-D68 antivirals by targeting various viral proteins and host factors that are essential for viral replication. The future directions of EV-D68 antiviral drug discovery and the criteria for drugs to reach clinical trials are also discussed.

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Section: Capsid Inhibitors (Vp1–vp4)mentioning

confidence: 99%

Enterovirus D68 Antivirals: Past, Present, and Future

Musharrafieh

Zheng

et al. 2020

ACS Infect. Dis.

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“…The structure of some viral coats was previously revealed [9]-even the cellular location of uncoating was identified for some viruses as well [10]. Zhang et al proposed an essential method for treating enterovirus 71 infection by preventing the uncoating process and stopping the hole formation on the membrane [11]. (3) By influencing the cytokines in the serum.…”

Section: The General Mechanism Of Neutralizing Antibody Fighting Agai...mentioning

confidence: 99%

A Comparative and Comprehensive Review of Antibody Applications in the Treatment of Lung Disease

Song

2022

Life

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Antibodies are a type of protein produced by active B cells in response to antigen stimulation. A series of monoclonal antibodies and neutralizing antibodies have been invented and put into clinical use because of their high therapeutic effect and bright developing insight. Patients with cancer, infectious diseases, and autoimmune diseases can all benefit from antibody therapy. However, the targeting aspects and potential mechanisms for treating these diseases differ. In the treatment of patients with infectious diseases such as COVID-19, neutralizing antibodies have been proposed as reliable vaccines against COVID-19, which target the ACE2 protein by preventing virus entry into somatic cells. Monoclonal antibodies can target immune checkpoints (e.g., PD-L1 and CTLA-4), tyrosine kinase and subsequent signaling pathways (e.g., VEGF), and cytokines in cancer patients (e.g. IL-6 and IL-1β). It is debatable whether there is any connection between the use of antibodies in these diseases. It would be fantastic to discover the related points and explain the burden for the limitation of cross-use of these techniques. In this review, we provided a comprehensive overview of the use of antibodies in the treatment of infectious disease and cancer patients. There are also discussions of their mechanisms and history. In addition, we discussed our future outlook on the use of antibodies.

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“…The latter similarly impedes the transition from the native virus into the A (i.e., ‘altered’ or ‘activated’) particle. Research along these lines is still active, and novel EV-A71 neutralising compounds, employing similar mechanisms, have recently been reported but not tested against RVs [ 42 ]. The feeble stabilisation of the virion by the natural pocket factors is useful to prevent premature uncoating.…”

Section: Targeting the Viral Capsidmentioning

confidence: 99%

Rhinovirus Inhibitors: Including a New Target, the Viral RNA

Real-Hohn

Blaas

2021

Viruses

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Rhinoviruses (RVs) are the main cause of recurrent infections with rather mild symptoms characteristic of the common cold. Nevertheless, RVs give rise to enormous numbers of absences from work and school and may become life-threatening in particular settings. Vaccination is jeopardised by the large number of serotypes eliciting only poorly cross-neutralising antibodies. Conversely, antivirals developed over the years failed FDA approval because of a low efficacy and/or side effects. RV species A, B, and C are now included in the fifteen species of the genus Enteroviruses based upon the high similarity of their genome sequences. As a result of their comparably low pathogenicity, RVs have become a handy model for other, more dangerous members of this genus, e.g., poliovirus and enterovirus 71. We provide a short overview of viral proteins that are considered potential drug targets and their corresponding drug candidates. We briefly mention more recently identified cellular enzymes whose inhibition impacts on RVs and comment novel approaches to interfere with infection via aggregation, virus trapping, or preventing viral access to the cell receptor. Finally, we devote a large part of this article to adding the viral RNA genome to the list of potential drug targets by dwelling on its structure, folding, and the still debated way of its exit from the capsid. Finally, we discuss the recent finding that G‑quadruplex stabilising compounds impact on RNA egress possibly via obfuscating the unravelling of stable secondary structural elements.

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Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease

Cited by 14 publications

References 36 publications

Enterovirus D68 Antivirals: Past, Present, and Future

Enterovirus D68 Antivirals: Past, Present, and Future

A Comparative and Comprehensive Review of Antibody Applications in the Treatment of Lung Disease

Rhinovirus Inhibitors: Including a New Target, the Viral RNA

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