Potent Molecular Feature-based Neutralizing Monoclonal Antibodies as Promising Therapeutics Against SARS-CoV-2 Infection.
KOMBE KOMBE A,J,. et al.’s new published article entitled “Potent Molecular Feature-based Neutralizing Monoclonal Antibodies as Promising Therapeutics Against SARS-CoV-2 Infection”, was accepted on May 6th, 2021 in Frontiers in Molecular Biosciences, and became available online since May 31st 2021 (https://www.frontiersin.org/articles/10.3389/fmolb.2021.670815/full).
Professors Jin Tengchuan and Shi Ronghua are the corresponding authors.
Keywords: MERS-CoV; SARS-CoV; SARS-CoV-2; antibody cocktail; cross-neutralizing antibody; molecular mechanism of action; neutralizing monoclonal antibody.
The high human-to-human transmission ability of SARS-CoV-2 led to a fast worldwide spread and has caused substantial human loss. Mechanical antiviral control approach, drug repositioning, and use of COVID-19 convalescent plasmas (CPs) were the first line strategies utilized to mitigate the viral spread, yet insufficient. The urgent need to contain this deadly pandemic has led searchers and pharmaceutical companies to develop vaccines. However, not all vaccines manufactured are safe. Besides, an alternative and effective treatment option for such an infectious disease would include pure anti-viral neutralizing monoclonal antibodies (NmAbs), which can block the virus at specific molecular targets from entering cells by inhibiting virus-cell structural complex formation, with more safety and efficiency than the CP. Indeed, there is a lot of molecular evidence about the protector effect and the use of molecular feature-based NmAbs as promising therapeutics to contain COVID-19. Thus, we here made a repertory of characterized NmAbs against SARS-CoV-2, their molecular neutralization mechanisms, and their immunotherapeutic effects. At the writing time (January 2021), all retrieved NmAbs bind at different sites of SARS-CoV-2 S and exhibit high molecular neutralizing effects against wild-type and/or pseudotyped virus. Based on their binding characteristics, we defined six NmAb groups blocking SARS-CoV-2 through different molecular neutralization mechanisms, from which five potential neutralization sites on SARS-CoV-2 S protein are described. This provides evidence in developing NmAbs-based cocktails from different Abs groups to mitigate COVID-19.
Top NmAbs in advanced clinical trial phase III and the potential NmAbs for efficient cocktail formulation. The need for potential emergency treatment for COVID-19 has birthed a dozen antibodies in clinical trials. The most advanced of them are in clinical trial phase III, and they include: i) REGN10933+REGN10987 (clinicaltrials.gov; ID: NCT04452318), sponsored by Regeneron Pharmaceuticals; ii) LY-CoV555+LY-CoV016 (LY3819253+LY3832479) (clinicaltrials.gov; ID: NCT04427501), sponsored by Eli Lilly and Company of Indianapolis; iii) LY-CoV555 (LY3819253) (clinicaltrials.gov; ID: NCT04497987), sponsored by Eli Lilly and Company of Indianapolis; iv) VIR-7831 (fully NmAb engineered from S309 features) (clinicaltrials.gov; ID: NCT04545060), sponsored by Vir biotechnology and GSK.
