Treatment and prevention strategies for the COVID 19 pandemic: A review of immunotherapeutic approaches for neutralizing SARS-CoV-2

Baral, Pravas Kumar; Jiang, Yin; James, Michael N.G.

doi:10.1016/j.ijbiomac.2021.07.013

Cited by 30 publications

(25 citation statements)

References 97 publications

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“…Current treatment strategies for COVID-19 are mainly focused on chemical medicines, including various neutralizing antibodies [13,18,19]. Thus, it is important to characterize inhibitory chemicals such as antibodies and drugs to prevent SARS-CoV-2 infection [20].…”

Section: Introductionmentioning

confidence: 99%

Interaction between Spike Protein of SARS-CoV-2 and Human Virus Receptor ACE2 Using Two-Color Fluorescence Cross-Correlation Spectroscopy

et al. 2021

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Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is initiated by the interaction between a receptor protein, angiotensin-converting enzyme type 2 (ACE2) on the cell surface, and the viral spike (S) protein. This interaction is similar to the mechanism in SARS-CoV, a close relative of SARS-CoV-2, which was identified in 2003. Drugs and antibodies that inhibit the interaction between ACE2 and S proteins could be key therapeutic methods for preventing viral infection and replication in COVID-19. Here, we demonstrate the interaction between human ACE2 and a fragment of the S protein (S1 subunit) derived from SARS-CoV-2 and SARS-CoV using two-color fluorescence cross-correlation spectroscopy (FCCS), which can detect the interaction of fluorescently labeled proteins. The S1 subunit of SARS-CoV-2 interacted in solution with soluble ACE2, which lacks a transmembrane region, more strongly than that of SARS-CoV. Furthermore, one-to-one stoichiometry of the two proteins during the interaction was indicated. Thus, we propose that this FCCS-based interaction detection system can be used to analyze the interaction strengths of various mutants of the S1 subunit that have evolved during the worldwide pandemic, and also offers the opportunity to screen and evaluate the performance of drugs and antibodies that inhibit the interaction.

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Section: Introductionmentioning

confidence: 99%

Interaction between Spike Protein of SARS-CoV-2 and Human Virus Receptor ACE2 Using Two-Color Fluorescence Cross-Correlation Spectroscopy

et al. 2021

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“…Several neutralizing monoclonal antibodies targeting various epitopes on the SARS-CoV-2 spike protein are under investigation ( 13 – 15 ). Bamlanvimab (LY-CoV555) with or without the combination of etesevimab (LY-CoV06 or JS016) decreased viral load and risk of COVID-19 related hospitalization among outpatients compared with those who received placebo but did not improve clinical outcomes among hospitalized patients ( 16 – 19 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody JS016 in Hospitalized Chinese Patients with COVID-19: a Phase 2/3, Multicenter, Randomized, Open-Label, Controlled Trial

Dong

Jiang

Yang

et al. 2022

Antimicrob Agents Chemother

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Recombinant human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody JS016 showed neutralizing and therapeutic effects in preclinical studies. The clinical efficacy and safety of the therapy needed to be evaluated. In this phase2/3, multicenter, randomized, open-label, controlled trial, hospitalized patients with moderate or severe coronavirus disease 2019 (COVID-19) were randomly assigned in a 1:1 ratio to receive standard care or standard care plus a single intravenous infusion of JS016. The primary outcome was a six-level ordinal scale of clinical status on 28 days since randomization. Secondary outcomes include adverse events, 28-day mortality, ventilator free days within 28 days, length of hospital stay, and negative conversion rate of SARS-CoV-2 nucleic acid on day 14. A total of 199 patients were randomized, and 197 (99 in JS016 group and 98 in control group) analysed. Most patients, 95 (96%) in JS016 group and 97 (99%) in control group, were in the best category on day 28 since randomization. The odds ratio of being in a better clinical status was 0.31 (95% confidence interval [CI], 0.03-3.19; p = 0.33). Few adverse events occurred in both groups (3% in JS016 group and 1% in control group, respectively; p = 0.34). SARS-CoV-2 neutralizing antibody JS016 did not show clinical efficacy among hospitalized Chinese patients with moderate to severe COVID-19 disease. Further studies are needed to assess the efficacy of the neutralizing antibody to prevent disease deterioration and its benefits among groups of patients specified by disease course and severity. (This study has been registered at ClinicalTrials.gov under identifier NCT04931238.)

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“…Preliminary in vitro evidence suggests continued antiviral activity against commonly circulating variants from the U.K. and South Africa ( Yang et al., 2020 ). A phase 1 study completed dosing and follow-up by providing safety profiles and human pharmacokinetic profiles for two separate antibodies ( Baral et al., 2021 ). Combination therapy consisting of BRII196 and BRII198 was originally investigated in the April 2021 NIAID ACTIV3 study (NCT04501978) in inpatients.…”

Section: Brii-196/brii-198mentioning

confidence: 99%

“…However, it did not meet the pre-determined performance criteria required for Phase 3 entry. As part of an ongoing NIH ACTIV2 trial (NCT04518410), a mixture of BRII196 and BRII198 antibodies is in phase 3 clinical trials ( Baral et al., 2021 ).…”

Section: Brii-196/brii-198mentioning

confidence: 99%

SARS-CoV-2: Recent Variants and Clinical Efficacy of Antibody-Based Therapy

Singh

Sharma

Lee

et al. 2022

Front. Cell. Infect. Microbiol.

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Multiple variants of SARS-CoV-2 have emerged and are now prevalent at the global level. Currently designated variants of concern (VOCs) are B.1.1.7, B1.351, P.1, B.1.617.2 variants and B.1.1.529. Possible options for VOC are urgently required as they carry mutations in the virus spike protein that allow them to spread more easily and cause more serious illness. The primary targets for most therapeutic methods against SARS-CoV-2 are the S (Spike) protein and RBD (Receptor-Binding Domain), which alter the binding to ACE2 (Angiotensin-Converting Enzyme 2). The most popular of these strategies involves the use of drug development targeting the RBD and the NTD (N-terminal domain) of the spike protein and multiple epitopes of the S protein. Various types of mutations have been observed in the RBDs of B.1.1.7, B1.351, P. and B.1.620. The incidence of RBD mutations increases the binding affinity to the ACE2 receptor. The high binding affinity of RBD and ACE2 has provided a structural basis for future evaluation of antibodies and drug development. Here we discuss the variants of SARS-CoV-2 and recent updates on the clinical evaluation of antibody-based treatment options. Presently, most of the antibody-based treatments have been effective in patients with SARS-CoV-2. However, there are still significant challenges in verifying independence, and the need for further clinical evaluation.

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Treatment and prevention strategies for the COVID 19 pandemic: A review of immunotherapeutic approaches for neutralizing SARS-CoV-2

Cited by 30 publications

References 97 publications

Interaction between Spike Protein of SARS-CoV-2 and Human Virus Receptor ACE2 Using Two-Color Fluorescence Cross-Correlation Spectroscopy

Interaction between Spike Protein of SARS-CoV-2 and Human Virus Receptor ACE2 Using Two-Color Fluorescence Cross-Correlation Spectroscopy

Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody JS016 in Hospitalized Chinese Patients with COVID-19: a Phase 2/3, Multicenter, Randomized, Open-Label, Controlled Trial

SARS-CoV-2: Recent Variants and Clinical Efficacy of Antibody-Based Therapy

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