A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV

Zhao, Guangyu; He, Lihua; Sun, Shihui; Qiu, Hongjie; Tai, Wanbo; Chen, Jiawei; Li, Jiangfan; Chen, Yuehong; Guo, Yan; Wang, Yufei; Shang, Jian; Ji, Kaiyuan; Fan, Ruiwen; Wang, Jianxiao; Jiang, Shibo; Li, Fang; Du, Lanying; Zhou, Yusen

doi:10.1128/jvi.00837-18

Cited by 90 publications

(98 citation statements)

References 55 publications

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“…Antibodies against RBD and S2 domain of SARS-CoV and MERS-CoV S proteins have been found effective in neutralizing infections of permissive cell lines in vitro [52][53][54][55]. In addition, neutralizing antibodies were capable of treating infections in experimental animals and in infected patients during these major outbreaks [56][57][58][59]. In one study, several SARS-CoV RBD-specific monoclonal antibodies did not bind to SARS-CoV-2 S protein [43].…”

Section: Of 15mentioning

confidence: 99%

Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks

et al. 2020

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Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.

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Section: Of 15mentioning

confidence: 99%

Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks

et al. 2020

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“…The mice were injected with a single dose NbMS10-FC or Trastuzumab (control group) before a lethal dose of MESR-CoV. The treatment group had a 100% survival rate compared with 0% survival rate in the control group [56].…”

Section: Animal Studiesmentioning

confidence: 99%

A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Momattin

Al-Ali

Al‐Tawfiq

2019

Travel Medicine and Infectious Disease

114

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Direct. Based on the inclusions and exclusions criteria, 30 articles were included in the final review and comprised: 22 in vitro studies, 8 studies utilizing animal models, 13 studies in humans, and one study included both in vitro and animal model. There are a few promising therapeutic agents on the horizon. The combination of lopinavir/ritonavir and interferon-beta-1b showed excellent results in common marmosets and currently is in a randomized control trial. Ribavirin and interferon were the most widely used combination and experience comes from a number of observational studies. Although, the data are heterogenous, this combination might be of potential benefit and deserve further investigation. There were no randomized clinical trials to recommend specific therapy for the treatment of MERS-CoV infection. Only one such study is planned for randomization and is pending completion. The study is based on a combination of lopinavir/ritonavir and interferon-beta-1b. A fully human polyclonal IgG antibody (SAB-301) was safe and well tolerated in healthy individuals and this agent may deserve further testing for efficacy. Conclusion: Despite multiple studies in humans there is no consensus on the optimal therapy for MERS-CoV. Randomized clinical trials are needed and potential therapies should be evaluated only in such clinical trials. In order to further enhance the therapeutic aroma for MERS-CoV infection, repurposing old drugs against MERS-CoV is an interesting strategy and deserves further consideration and use in clinical settings.

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“…Apart from the necessity of setting new ad hoc infrastructures, new approaches require protocol optimization and troubleshooting capacity, as underlined by the report indicating that P. pastoris strains are prone to mis-incorporate amino acids under specific fermentation conditions [68]. Pichia has been successfully used to produce a nanobody and its corresponding human Fc-fusion that target the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) receptor-binding domain [69]. Both constructs are characterized by a strong neutralizing activity but, unluckily, the authors' claim concerning the economic reason for choosing this expression system was not supported by experimental data and comparison with alternative methods.…”

Section: Other Eukaryotic Systemsmentioning

confidence: 99%

Recombinant expression of nanobodies and nanobody-derived immunoreagents

Marco

2020

Protein Expression and Purification

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A B S T R A C TAntibody fragments for which the sequence is available are suitable for straightforward engineering and expression in both eukaryotic and prokaryotic systems. When produced as fusions with convenient tags, they become reagents which pair their selective binding capacity to an orthogonal function. Several kinds of immunoreagents composed by nanobodies and either large proteins or short sequences have been designed for providing inexpensive ready-to-use biological tools. The possibility to choose among alternative expression strategies is critical because the fusion moieties might require specific conditions for correct folding or posttranslational modifications. In the case of nanobody production, the trend is towards simpler but reliable (bacterial) methods that can substitute for more cumbersome processes requiring the use of eukaryotic systems. The use of these will not disappear, but will be restricted to those cases in which the final immunoconstructs must have features that cannot be obtained in prokaryotic cells. At the same time, bacterial expression has evolved from the conventional procedure which considered exclusively the nanobody and nanobody-fusion accumulation in the periplasm. Several reports show the advantage of cytoplasmic expression, surface-display and secretion for at least some applications. Finally, there is an increasing interest to use as a model the short nanobody sequence for the development of in silico methodologies aimed at optimizing the yields, stability and affinity of recombinant antibodies.

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A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV

Cited by 90 publications

References 55 publications

Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks

Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks

A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Recombinant expression of nanobodies and nanobody-derived immunoreagents

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