Potent mouse monoclonal antibodies that block SARS-CoV-2 infection

Guo, Youjia; Kawaguchi, Atsushı; Takeshita, Masaru; Sekiya, Takeshi; Hirohama, Mikako; Yamashita, Akio; Siomi, Haruhiko; Murano, Kensaku

doi:10.1101/2020.10.01.323220

Cited by 8 publications

(9 citation statements)

References 57 publications

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“…Accordingly, COVID-19 research has not excluded hybridomas, as there are multiple studies using this strategy for treating SARS-CoV-2 infection [ 12 , 227 – 230 ]. In recent studies, Abs from hybridomas with the ability to cross-neutralize SARS-CoV and SARS-CoV-2 in vitro have been identified [ 12 , 227 , 229 ], similar to those previously reported in terms of cross-neutralization amongst different CoVs (SARS-CoV, MERS-CoV, and SARS-CoV-2) [ 3 , 29 , 135 , 231 , 232 ].…”

Section: Insights From Ab Therapeutic Strategies Against Sars-cov-2 Infectionsupporting

confidence: 69%

“…Additionally, IgA is proposed to have a greater persistence in mucosal secretions compared with the other isotypes [ 227 ]. Another mAb obtained from hybridoma cells is mAb#11/9, which binds the S protein irrespective of its glycosylation pattern [ 228 ], being also recognized by Abs SiD7h and S3D8h (IC 50 of 113.3 ng/mL and 137.2 ng/mL, respectively) [ 229 ]. Furthermore, six groups of mice hybridoma Abs with neutralizing capacity that recognized different epitopes on RBD has been described and can be employed as diagnostic tools in SARS-CoV-2 infection [ 230 ].…”

Section: Insights From Ab Therapeutic Strategies Against Sars-cov-2 Infectionmentioning

confidence: 99%

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Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment

et al. 2021

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SARS-CoV-2 is a novel β-coronavirus that caused the COVID-19 pandemic disease, which spread rapidly, infecting more than 134 million people, and killing almost 2.9 million thus far. Based on the urgent need for therapeutic and prophylactic strategies, the identification and characterization of antibodies has been accelerated, since they have been fundamental in treating other viral diseases. Here, we summarized in an integrative manner the present understanding of the immune response and physiopathology caused by SARS-CoV-2, including the activation of the humoral immune response in SARS-CoV-2 infection and therefore, the synthesis of antibodies. Furthermore, we also discussed about the antibodies that can be generated in COVID-19 convalescent sera and their associated clinical studies, including a detailed characterization of a variety of human antibodies and identification of antibodies from other sources, which have powerful neutralizing capacities. Accordingly, the development of effective treatments to mitigate COVID-19 is expected. Finally, we reviewed the challenges faced in producing potential therapeutic antibodies and nanobodies by cell factories at an industrial level while ensuring their quality, efficacy, and safety.

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Section: Insights From Ab Therapeutic Strategies Against Sars-cov-2 Infectionsupporting

confidence: 69%

Section: Insights From Ab Therapeutic Strategies Against Sars-cov-2 Infectionmentioning

confidence: 99%

Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment

et al. 2021

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“…The homotrimeric spike protein is possibly the most important of these and plays a definitive role in the viral infection process by mediating recognition of the host cell receptors 13, 15–17 . For this reason, the spike protein of SARS-CoV-2 is the primary target of several ongoing structure-based drug and vaccine design studies 18–23 . Several vaccines have recently been approved for use in different countries, including the mRNA-based Pfizer and Moderna vaccines 24–26 .…”

Section: Introductionmentioning

confidence: 99%

Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2

Kumar

Ogden

Isu

et al. 2020

Preprint

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Within the last two decades, severe acute respiratory syndrome (SARS) coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) have caused two major outbreaks. For reasons yet to be fully understood the COVID-19 outbreak caused by SARS-CoV-2 has been significantly more widespread than the 2003 SARS epidemic caused by SARS-CoV-1, despite striking similarities between the two viruses. One of the most variable genes differentiating SARS-CoV-1 and SARS-CoV-2 is the S gene that encodes the spike glycoprotein. This protein mediates a crucial step in the infection, i.e., host cell recognition and viral entry, which starts with binding to the host cell angiotensin converting enzyme 2 (ACE2) protein for both viruses. Recent structural and functional studies have shed light on the differential binding behavior of the SARS-CoV-1 and SARS-CoV-2 spike proteins. In particular, cryogenic electron microscopy (cryo-EM) studies show that ACE2 binding is preceded by a large-scale conformational change in the spike protein to expose the receptor binding domain (RBD) to its binding partner. Unfortunately, these studies do not provide detailed information on the dynamics of this activation process. Here, we have used an extensive set of unbiased and biased microsecond-timescale all-atom molecular dynamics (MD) simulations of SARS-CoV-1 and SARS-CoV-2 spike protein ectodomains in explicit solvent to determine the differential behavior of spike protein activation in the two viruses. Our results based on nearly 50 microseconds of equilibrium and nonequilibrium MD simulations indicate that the active form of the SARS-CoV-2 spike protein is considerably more stable than the active SARS-CoV-1 spike protein. Unlike the active SARS-CoV-2 spike, the active SARS-CoV-1 spike spontaneously undergoes a large-scale conformational transition to a pseudo-inactive state, which occurs in part due to interactions between the N-terminal domain (NTD) and RBD that are absent in the SARS-CoV-2 spike protein. Steered MD (SMD) simulations indicate that the energy barriers between active and inactive states are comparatively lower for the SARS-CoV-1 spike protein. Based on these results, we hypothesize that the greater propensity of the SARS-CoV-2 spike protein to remain in the active conformation contributes to the higher transmissibility of SARS-CoV-2 in comparison to SARS-CoV-1. These results strongly suggest that the differential binding behavior of the active SARS-CoV-1 and 2 spike proteins is not merely due to differences in their RBDs as other domains of the spike protein such as the NTD could play a crucial role in the effective binding process, which involves the prebinding activation. Therefore, our hypothesis predicts that mutations in regions such as the NTD, which is not directly involved in binding, may lead to a change in the effective binding behavior of the coronavirus.

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“…The efficacy of mAbs in convalescent plasma differs between donors; following selection, mAb therapy could be prepared as an off-the-shelf product from the most potent mAb combinations against SARS-CoV-2. Preliminary studies have yielded promising results in the search for mAb or mAb cocktails targeting the SARS-CoV-2 S-protein (81)(82)(83)(84)(85). These studies may also provide insight into vaccine design to determine which mAb will illicit the most potent SARS-CoV-2 neutralization in uninfected individuals (81).…”

Section: Monoclonal Antibody Specific To Sars-cov-2mentioning

confidence: 99%

The COVID-19 Treatment Landscape: A South African Perspective on a Race Against Time

et al. 2021

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The pandemic caused by SARS-CoV-2 has infected more than 94 million people worldwide (as of 17 January 2020). Severe disease is believed to be secondary to the cytokine release syndrome (CRS or “cytokine storm”) which causes local tissue damage as well as multi-organ dysfunction and thrombotic complications. Due to the high mortality rates in patients receiving invasive ventilation, practice has changed from “early-intubation” for acute respiratory distress syndrome (ARDS) to a trial of non-invasive ventilation (NIV) or high flow nasal cannula (HFNC) oxygen. Reports indicating the benefit of NIV and HFNC have been encouraging and have led to more than 20,000 such devices being manufactured and ready for roll-out in South Africa (SA) as of July 2020. The need to identify drugs with clear clinical benefits has led to an array of clinical trials, most of which are repurposing drugs for COVID-19. The treatment landscape reflects the need to target both the virus and its effects such as the CRS and thrombotic complications. Conflicting results have the potential to confuse the implementation of coordinated treatment strategies and guidelines. The purpose of this review is to address pertinent areas in the current literature on the available medical treatment options for COVID-19. Remdesivir, tocilizumab, and dexamethasone are some of the treatment options that have shown the most promise, but further randomized trials are required to particularly address timing and dosages to confidently create standardized protocols. For the SA population, two healthcare sectors exist. In the private sector, patients with medical insurance may have greater access to a wider range of treatment options than those in the public sector. The latter serves >80% of the population, and resource constraints require the identification of drugs with the most cost-effective use for the greatest number of affected patients.

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Potent mouse monoclonal antibodies that block SARS-CoV-2 infection

Cited by 8 publications

References 57 publications

Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment

Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment

Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2

The COVID-19 Treatment Landscape: A South African Perspective on a Race Against Time

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