scholarly journals The emergence of SARS-CoV-2 variants threatens to decrease the efficacy of neutralizing antibodies and vaccines

2021 ◽  
Author(s):  
Kensaku Murano ◽  
Youjia Guo ◽  
Haruhiko Siomi
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
The Novel ◽  
Therapeutic Antibodies ◽  
Human Origin ◽  
New Challenges ◽  
Novel Coronavirus

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease (COVID-19) pandemic. As of August 2021, more than 200 million people have been infected with the virus and 4.3 million have lost their lives. Various monoclonal antibodies of human origin that neutralize the SARS-CoV-2 infection have been isolated from convalescent patients for therapeutic and prophylactic purposes. Several vaccines have been developed to restrict the spread of the virus and have been rapidly administered. However, the rollout of vaccines has coincided with the spread of variants of concern. Emerging variants of SARS-CoV-2 present new challenges for therapeutic antibodies and threaten the efficacy of current vaccines. Here, we review the problems faced by neutralizing antibodies and vaccines in the midst of the increasing spread of mutant viruses.

scholarly journals Mutations in SARS-CoV-2 Variants Modulate the Microscopic Dynamics of Neutralizing Antibodies

2021 ◽  
Author(s):  
Dhiman Ray ◽  
Riley Nicolas Quijano ◽  
Ioan Andricioaei
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Rational Design ◽  
Graph Connectivity ◽  
World Population ◽  
The Novel ◽  
Long Distance ◽  
Correlated Motion ◽  
Novel Coronavirus ◽  
Microscopic Dynamics

Monoclonal antibodies have emerged as viable treatment for the COVID-19 disease caused by the SARS-CoV-2 virus. But the new viral variants can reduce the efficacy of the currently available antibodies, as well as diminish the vaccine induced immunity. Here, we demonstrate how the microscopic dynamics of the SARS-CoV-2 neutralizing monoclonal antibodies, can be modulated by the mutations present in the spike proteins of the variants currently circulating in the world population. We show that the dynamical perturbation in the antibody structure can be diverse, depending both on the nature of the antibody and on the location of the mutation. The correlated motion between the antibody and the receptor binding domain (RBD) can also be changed, altering the binding affinity. By constructing a protein graph connectivity network, we could delineate the mutant induced modifications in the allosteric information flow pathway through the antibody, and observed the presence of both localized and long distance effects. We identified a loop consisting of residues 470-490 in the RBD which works like an anchor preventing the detachment of the antibodies, and individual mutations in that region can significantly affect the antibody binding propensity. Our study provides fundamental and atomistically detailed insight on how virus neutralization by monoclonal antibody can be impacted by the mutations in the epitope, and can potentially facilitate the rational design of monoclonal antibodies, effective against the new variants of the novel coronavirus.

scholarly journals Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants

2021 ◽  
Vol 12 ◽  
Author(s):  
Lok Bahadur Shrestha ◽  
Nicodemus Tedla ◽  
Rowena A. Bull
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Second Generation ◽  
Therapeutic Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
Escape Mutants ◽  
Cross Neutralization ◽  
A Priority ◽  
Therapeutic Monoclonal Antibodies

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have become a major concern in the containment of current pandemic. The variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta) have shown reduced sensitivity to monoclonal antibodies, plasma and/or sera obtained from convalescent patients and vaccinated individuals. Development of potent therapeutic monoclonal antibodies (mAbs) with broad neutralizing breadth have become a priority for alleviating the devastating effects of this pandemic. Here, we review some of the most promising broadly neutralizing antibodies obtained from plasma of patients that recovered from early variants of SARS-CoV-2 that may be effective against emerging new variants of the virus. This review summarizes several mAbs, that have been discovered to cross-neutralize across Sarbecoviruses and SARS-CoV-2 escape mutants. Understanding the characteristics that confer this broad and cross-neutralization functions of these mAbs would inform on the development of therapeutic antibodies and guide the discovery of second-generation vaccines.

scholarly journals Severe neutropenia in infants with severe acute respiratory syndrome caused by the novel coronavirus 2019 infection

2020 ◽  
Vol 222 ◽  
pp. 259-261 ◽  
Author(s):  
Elisabetta Venturini ◽  
Giordano Palmas ◽  
Carlotta Montagnani ◽  
Elena Chiappini ◽  
Francesco Citera ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Severe Neutropenia ◽  
The Novel ◽  
Novel Coronavirus

scholarly journals Comparison of Four SARS-CoV-2 Neutralization Assays

Vaccines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 13
Author(s):  
Lydia Riepler ◽  
Annika Rössler ◽  
Albert Falch ◽  
André Volland ◽  
Wegene Borena ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
The Other ◽  
In Vitro Assays ◽  
The Novel ◽  
Effective Protection ◽  
Vaccine Candidates ◽  
Vesicular Stomatitis ◽  
Novel Coronavirus

Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.

scholarly journals Murine monoclonal antibodies against RBD of SARS-CoV-2 neutralize authentic wild type SARS-CoV-2 as well as B.1.1.7 and B.1.351 viruses and protect in vivo in a mouse model in a neutralization dependent manner

2021 ◽  
Author(s):  
Fatima Amanat ◽  
Shirin Strohmeier ◽  
Wen-Hsin Lee ◽  
Sandhya Bangaru ◽  
Andrew B Ward ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Dependent Manner ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Murine Monoclonal Antibodies

After first emerging in December 2019 in China, severe acute respiratory syndrome 2 (SARS-CoV-2) has since caused a pandemic leading to millions of infections and deaths worldwide. Vaccines have been developed and authorized but supply of these vaccines is currently limited. With new variants of the virus now emerging and spreading globally, it is essential to develop therapeutics that are broadly protective and bind conserved epitopes in the receptor binding domain (RBD) or the whole spike of SARS-CoV-2. In this study, we have generated mouse monoclonal antibodies (mAbs) against different epitopes on the RBD and assessed binding and neutralization against authentic SARS-CoV-2. We have demonstrated that antibodies with neutralizing activity, but not non-neutralizing antibodies, lower viral titers in the lungs when administered in a prophylactic setting in vivo in a mouse challenge model. In addition, most of the mAbs cross-neutralize the B.1.351 as well as the B.1.1.7 variants in vitro.

scholarly journals Does the novel coronavirus 2019 like heart more than the other family members of coronaviruses?

2020 ◽  
Vol 12 (2) ◽  
pp. 156-157
Author(s):  
Mohammad Mostafa Ansari Ramandi ◽  
Mohammadreza Baay ◽  
Nasim Naderi
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Family Members ◽  
Middle East Respiratory Syndrome ◽  
The Other ◽  
The Novel ◽  
The World ◽  
Future Challenges ◽  
Novel Coronavirus ◽  
Coronavirus Infections

The disaster due to the novel coronavirus disease 2019 (COVID-19) around the world has made investigators enthusiastic about working on different aspects of COVID-19. However, although the pandemic of COVID-19 has not yet ended, it seems that COVID-19 compared to the other coronavirus infections (the Middle East Respiratory Syndrome [MERS] and Severe Acute Respiratory Syndrome [SARS]) is more likely to target the heart. Comparing the previous presentations of the coronavirus family and the recent cardiovascular manifestations of COVID-19 can also help in predicting possible future challenges and taking measures to tackle these issues.

scholarly journals Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Satoshi Ikegame ◽  
Mohammed Siddiquey ◽  
Chuan-Tien Hung ◽  
Griffin Haas ◽  
Luca Brambilla ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Cell Line ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
The Novel ◽  
Serum Samples ◽  
Egfp Reporter ◽  
Vesicular Stomatitis ◽  
Reduced Activity

Abstract The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China1,2. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales have prompted re-evaluation of strategies to achieve universal vaccination3. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic4–8. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that only 1 out of 12 serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.

scholarly journals Respiratory Care in Corona

2021 ◽  
Vol 58 (2) ◽  
pp. 613-620
Author(s):  
Mustafa Amdani, Dr. Swaroopa Chakole
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Human Life ◽  
The Body ◽  
Respiratory Care ◽  
The Novel ◽  
Specific Therapy ◽  
History Of ◽  
Novel Coronavirus ◽  
Almost All ◽  
The Impact

BACKGROUND The expanse of the coronavirus disease 2019 or COVID-19 is huge. The impact is multispectral and affected almost all aspects of human life. SUMMARY Respiratory impact of the COVID-19 is the most felt and widely reported impact. As the novel coronavirus maintained its history of affecting lungs as seen previously in severe acute respiratory syndrome (SARS) outbreak. Ventilators and oxygen support system are required mostly in comorbid patients particularly amongpatientsbearing illnesses like asthma, bronchial impairment and so on. CONCLUSION More study needs to be done in order to assess the impact on the respiratory functioning of the body. Respiratory care must be including proper instruments so that more efficient result can be obtained. Research is needed to promote the invention of specific therapy for targeted action for respiratory functioning improvement.

Tri-primer-enhanced strand exchange amplification combined with rapid lateral flow fluorescent immunoassay to detect SARS-CoV-2

The Analyst ◽  
2021 ◽  
Author(s):  
Linlin Zhuang ◽  
Jiansen Gong ◽  
Ming Ma ◽  
Yongxin Ji ◽  
Peilong Tian ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Lateral Flow ◽  
Strand Exchange ◽  
The Novel ◽  
The World ◽  
Novel Coronavirus

The novel coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been surging rapidly around the world, which exposes humanity to unprecedented economic, social and...

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