Perspectives on the use and risk of adverse events associated with cytokine-storm targeting antibodies and challenges associated with development of novel monoclonal antibodies for the treatment of COVID-19 clinical cases

Johnson, Aishwarya Mary; Barigye, Robert; Saminathan, Hariharan

doi:10.1080/21645515.2021.1908060

Cited by 9 publications

(4 citation statements)

References 155 publications

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“…Monoclonal antibodies exert a variety of effects depending on the individuals and stages of viremia. Pharmacokinetics discrepancy complicates determining mAb dosage ( Johnson et al, 2021 ), whether monoclonal antibodies are suitable for all COVID-19 patients, and achieving precise treatment and customized medication. Furthermore, mAb preparation technology is complicated, requiring a great deal of time, labor, and money.…”

Section: Future Challengesmentioning

confidence: 99%

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

et al. 2023

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COVID-19 pandemic is a global public health emergency. Despite extensive research, there are still few effective treatment options available today. Neutralizing-antibody-based treatments offer a broad range of applications, including the prevention and treatment of acute infectious diseases. Hundreds of SARS-CoV-2 neutralizing antibody studies are currently underway around the world, with some already in clinical applications. The development of SARS-CoV-2 neutralizing antibody opens up a new therapeutic option for COVID-19. We intend to review our current knowledge about antibodies targeting various regions (i.e., RBD regions, non-RBD regions, host cell targets, and cross-neutralizing antibodies), as well as the current scientific evidence for neutralizing-antibody-based treatments based on convalescent plasma therapy, intravenous immunoglobulin, monoclonal antibodies, and recombinant drugs. The functional evaluation of antibodies (i.e., in vitro or in vivo assays) is also discussed. Finally, some current issues in the field of neutralizing-antibody-based therapies are highlighted.

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Section: Future Challengesmentioning

confidence: 99%

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

et al. 2023

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“…The efficacy of monoclonal antibodies varies considerably depending on the individual and the stage of viraemia. Pharmacokinetic variations complicate the determination of appropriate mAbs dosages, 141 rendering it difficult to ascertain whether mAbs can be effectively and safely applied to every COVID‐19 patient, as well as to achieve precision, personalised therapy. Additionally, mAbs production technology is complex, demanding significant time, effort, and financial resources.…”

Section: Confronting Emerging Challengesmentioning

confidence: 99%

SARS‐CoV‐2 neutralising antibody therapies: Recent advances and future challenges

Liu

Liang

Cheng

et al. 2023

Reviews in Medical Virology

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The COVID‐19 pandemic represents an unparalleled global public health crisis. Despite concerted research endeavours, the repertoire of effective treatment options remains limited. However, neutralising‐antibody‐based therapies hold promise across an array of practices, encompassing the prophylaxis and management of acute infectious diseases. Presently, numerous investigations into COVID‐19‐neutralising antibodies are underway around the world, with some studies reaching clinical application stages. The advent of COVID‐19‐neutralising antibodies signifies the dawn of an innovative and promising strategy for treatment against SARS‐CoV‐2 variants. Comprehensively, our objective is to amalgamate contemporary understanding concerning antibodies targeting various regions, including receptor‐binding domain (RBD), non‐RBD, host cell targets, and cross‐neutralising antibodies. Furthermore, we critically examine the prevailing scientific literature supporting neutralising antibody‐based interventions, and also delve into the functional evaluation of antibodies, with a particular focus on in vitro (vivo) assays. Lastly, we identify and consider several pertinent challenges inherent to the realm of COVID‐19‐neutralising antibody‐based treatments, offering insights into potential future directions for research and development.

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“…We have also seen that there will not likely be a one-size-fits-all approach. While immunoglobulin-based therapeutic approaches have been beneficial for outpatient treatment [4], in patients at higher risk for severe disease [5,6], as well as in patients hospitalized with severe disease [7][8][9][10], these therapies have limitations [11][12][13][14]. They require a great deal of invested capital and healthcare infrastructure that may not be available to rural communities or developing parts of the world and may otherwise be prohibitively expensive.…”

Section: Introductionmentioning

confidence: 99%

Research Progress on Spike-Dependent SARS-CoV-2 Fusion Inhibitors and Small Molecules Targeting the S2 Subunit of Spike

Freidel,

Armen

2024

Viruses

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Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts have sought to identify small-molecule antivirals with various mechanisms of action. Here, we aim to review research progress on small-molecule viral entry and fusion inhibitors that directly bind to the SARS-CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in in vitro SARS-CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small-molecule binding sites on Spike, it was unclear what the specific mechanism of action was or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor-binding domain (RBD) or N-terminal domain (NTD) and disrupt the S1 receptor-binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most substitutions to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved, with only a few observed substitutions in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over recent VOC mutant strains and/or greater broad-spectrum antiviral activity for other more distantly related coronaviruses.

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Perspectives on the use and risk of adverse events associated with cytokine-storm targeting antibodies and challenges associated with development of novel monoclonal antibodies for the treatment of COVID-19 clinical cases

Cited by 9 publications

References 155 publications

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

SARS‐CoV‐2 neutralising antibody therapies: Recent advances and future challenges

Research Progress on Spike-Dependent SARS-CoV-2 Fusion Inhibitors and Small Molecules Targeting the S2 Subunit of Spike

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