Abstract
The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized controlled trial data evaluating nAbs in the ambulatory, hospitalized and prophylaxis settings. Two nAb cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab) and one nAb monotherapy (bamlanivimab) have been granted Emergency Use Authorization by the US Food and Drug Administration for the treatment of ambulatory patients who have a high risk of progressing to severe disease, and the European Medicines Agency has similarly recommended both cocktails and bamlanivimab monotherapy for use in COVID-19 patients who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Efficacy of nAbs in hospitalized patients with COVID-19 has been varied, potentially highlighting the challenges of antiviral treatment in patients who have already progressed to severe disease. However, early data suggest a promising prophylactic role for nAbs in providing effective COVID-19 protection. We also review the risk of treatment-emergent antiviral resistant “escape” mutants and strategies to minimize their occurrence, discuss the susceptibility of newly emerging SARS-COV-2 variants to nAbs, as well as explore administration challenges and ways to improve patient access.
Highlights
Se and 235 (“LALA mutants”) in the fragment crystallizable (Fc) portion of the neutralizing antibodies (nAbs) etesevimab (LY-CoV016) and breadth of promising pre-clinical evidence has so far resulted in nAbs being evaluated in various clinical trial settings [51]
The of RBD regions recognized by casirivimab (PDB: 6XDG), CT-P59 (PDB: 7CM4), imdevimab (PDB: RBD regions recognized by casirivimab (PDB: 6XDG), CT-P59 (PDB: 7CM4), imdev
Since the beginning of the COVID-19 pandemic, there has been a massive global effort to harness the potential of nAbs for inhibiting the SARS-CoV-2 virus
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In late 2019, the novel betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged from an animal reservoir into humans, causing a respiratory infection known as Coronavirus Disease 2019 (COVID-19) [1]. The high transmissibility and rapid global spread of SARS-CoV-2 has led to a worldwide COVID-19 pandemic that has continued for more than a year, leading to a huge burden on healthcare and society [2]. At the start of the pandemic, no evidence-based treatments were available for COVID19 despite the emergence and global spread of the related SARS-CoV-1 Pharmaceutical-grade monoclonal nAbs circumvent these limitations and have emerged as the first SARS-CoV-2–specific treatments to become available [16,19,20,21]. The challenges of drug resistance and approaches to improve the access and availability of nAbs in the future is discussed
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