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Review of COVID-19 Antibody Therapies.

ABSTRACT: In the global health emergency caused by coronavirus disease 2019 (COVID-19), efficient and specific therapies are urgently needed. Compared with traditional small-molecular drugs, antibody therapies are relatively easy to develop; they are as specific as vaccines in targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and they have thus attracted much attention in the past few months. This article reviews seven existing antibodies for neutralizing SARS-CoV-2 with 3D structures deposited in the Protein Data Bank (PDB). Five 3D antibody structures associated with the SARS-CoV spike (S) protein are also evaluated for their potential in neutralizing SARS-CoV-2. The interactions of these antibodies with the S protein receptor-binding domain (RBD) are compared with those between angiotensin-converting enzyme 2 and RBD complexes. Due to the orders of magnitude in the discrepancies of experimental binding affinities, we introduce topological data analysis, a variety of network models, and deep learning to analyze the binding strength and therapeutic potential of the 14 antibody-antigen complexes. The current COVID-19 antibody clinical trials, which are not limited to the S protein target, are also reviewed.

SUBMITTER: Chen J

PROVIDER: S-EPMC8155790 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Review of COVID-19 Antibody Therapies.

Chen Jiahui J Gao Kaifu K Wang Rui R Nguyen Duc Duy DD Wei Guo-Wei GW

Annual review of biophysics 20201016

In the global health emergency caused by coronavirus disease 2019 (COVID-19), efficient and specific therapies are urgently needed. Compared with traditional small-molecular drugs, antibody therapies are relatively easy to develop; they are as specific as vaccines in targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and they have thus attracted much attention in the past few months. This article reviews seven existing antibodies for neutralizing SARS-CoV-2 with 3D structure ...[more]

PMID: 33064571

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Project description:ObjectiveTo evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data.Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021).Study selectionTrials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate.MethodsAfter duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm.ResultsAs of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative.ConclusionIn patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit.Systematic review registrationThis review was not registered. The protocol established a priori is included as a data supplement.FundingThis study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321).Readers' noteThis article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).

Project description:Antibody therapeutics and vaccines are among our last resort to end the raging COVID-19 pandemic. They, however, are prone to over 5000 mutations on the spike (S) protein uncovered by a Mutation Tracker based on over 200 000 genome isolates. It is imperative to understand how mutations will impact vaccines and antibodies in development. In this work, we first study the mechanism, frequency, and ratio of mutations on the S protein which is the common target of most COVID-19 vaccines and antibody therapies. Additionally, we build a library of 56 antibody structures and analyze their 2D and 3D characteristics. Moreover, we predict the mutation-induced binding free energy (BFE) changes for the complexes of S protein and antibodies or ACE2. By integrating genetics, biophysics, deep learning, and algebraic topology, we reveal that most of the 462 mutations on the receptor-binding domain (RBD) will weaken the binding of S protein and antibodies and disrupt the efficacy and reliability of antibody therapies and vaccines. A list of 31 antibody disrupting mutants is identified, while many other disruptive mutations are detailed as well. We also unveil that about 65% of the existing RBD mutations, including those variants recently found in the United Kingdom (UK) and South Africa, will strengthen the binding between the S protein and human angiotensin-converting enzyme 2 (ACE2), resulting in more infectious COVID-19 variants. We discover the disparity between the extreme values of RBD mutation-induced BFE strengthening and weakening of the bindings with antibodies and angiotensin-converting enzyme 2 (ACE2), suggesting that SARS-CoV-2 is at an advanced stage of evolution for human infection, while the human immune system is able to produce optimized antibodies. This discovery, unfortunately, implies the vulnerability of current vaccines and antibody drugs to new mutations. Our predictions were validated by comparison with more than 1400 deep mutations on the S protein RBD. Our results show the urgent need to develop new mutation-resistant vaccines and antibodies and to prepare for seasonal vaccinations.

Project description:The urgent need for diagnostics and therapeutics against the COVID-19 pandemic has shown the great potential of antibodies, proteomics and metabolomics in this direction. Several clinical trials are underway using antibodies from COVID-19 patients that show very specific and strong binding to viral proteins leading to neutralization. On the other hand, proteomic and metabolomic profiles of COVID-19 patients present novel diagnostic biomarkers to predict patient outcomes and enable the development of personalized therapeutics to target the dysregulated pathways, as revealed by those profiles. Here, we discuss how studies based on antibodies, proteomics and metabolomics contribute to the development of diagnostics and therapeutics against COVID-19. The elegant technology can extend to high-throughput, rapid and reliable drug discovery strategies of the future. Lay abstract In order to prevent and treat the ongoing COVID-19 pandemic, several groups around the world are focused on a detailed understanding of the biology of SARS-CoV-2 infection, the biological events occurring inside the patients and the response of the patients to the infection. SARS-CoV-2 is the coronavirus that causes COVID-19. Some of the approaches to combat the pandemic have provided important results that can help toward therapeutic developments against COVID-19. This review discusses three such areas – antibody treatment to prevent COVID-19 infection, analysis of changes in protein profiles of COVID-19 patients, and analysis of metabolism or energy-related changes in COVID-19 patients. Antibodies are molecules produced in the host’s body as a defense response to infection. Antibodies extracted from patients who recovered from COVID-19 have been used to successfully manufacture large amounts of antibodies to treat COVID-19 patients. The analysis of protein and metabolism profiles of COVID-19 patients has shown that several proteins and metabolism-related entities in the body are either upregulated or downregulated in COVID-19. These abnormal levels can either be attenuated by medical intervention or can be monitored as indicators of COVID-19 diagnosis. Overall, antibodies, protein and metabolism profiles are three important tools, among several others, that are helpful in combating the COVID-19 pandemic.

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Review of COVID-19 Antibody Therapies.

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Review of COVID-19 Antibody Therapies.

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