scholarly journals Analyzing the interaction of human ACE2 and RBD of spike protein of SARS-CoV-2 in perspective of Omicron variant

2021 ◽  
Author(s):  
Arijit Samanta ◽  
Syed Sahajada Mahafujul Alam ◽  
Safdar Ali ◽  
Mehboob Hoque
Keyword(s):  
Protein Docking ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Amino Acid Residues ◽  
Angiotensin I ◽  
S Protein ◽  
Angiotensin I Converting Enzyme ◽  
Protein Receptor ◽  
New Variant ◽  
Unique Amino Acid

The newly identified Omicron (B.1.1.529) variant of Severe Acute Respiratory Syndrome Voronavirus 2 (SARS-CoV-2) has steered concerns across the world due to the possession of large number of mutations leading to high infectivity and vaccine escape potential. The Omicron variant houses 32 mutations in S protein alone. The viral infectivity is determined mainly by the ability of spike (S) protein receptor binding domain (RBD) to bind to the human Angiotensin I Converting Enzyme 2 (hACE2) receptor. In this paper, the interaction of the RBDs of SARS-CoV-2 variants with hACE2 was analyzed by using protein-protein docking and compared with the novel Omicron variant. Our findings reveal that the Omicron RBD interacts strongly with hACE2 receptor via unique amino acid residues as compared to the Wuhan and many other variants. However, the interacting residues of RBD are found to be the same in Lamda (C.37) variant. These unique binding of Omicron RBD with hACE2 suggests an increased potential of infectivity and vaccine evasion potential of the new variant. The evolutionary drive of the SARS-CoV-2 may not be exclusively driven by RBD variants but surely provides for the platform for emergence of new variants.

scholarly journals ACE2 polymorphisms as potential players in COVID-19 outcome

2020 ◽  
Author(s):  
André Salim Khayat ◽  
Paulo Pimentel de Assumpção ◽  
Bruna Claudia Meireles Khayat ◽  
Taíssa Maíra Thomaz Araújo ◽  
Jéssica Almeida Batista-Gomes ◽  
...  
Keyword(s):  
South American ◽  
Angiotensin I ◽  
Biological Aspect ◽  
Death Rates ◽  
Angiotensin I Converting Enzyme ◽  
Protein Receptor ◽  
Biological Explanation ◽  
The Many ◽  
Shed Light ◽  
Regulatory Sites

AbstractThe clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, ACE2 polymorphisms should influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.

scholarly journals Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Pranam Chatterjee ◽  
Manvitha Ponnapati ◽  
Christian Kramme ◽  
Alexandru M. Plesa ◽  
George M. Church ◽  
...  
Keyword(s):  
Computational Design ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Experimental Characterization ◽  
Viral Production ◽  
Health Crisis ◽  
Intracellular Degradation ◽  
Protein Receptor ◽  
Therapeutic Development ◽  
Novel Coronavirus

AbstractThe COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has elicited a global health crisis of catastrophic proportions. With only a few vaccines approved for early or limited use, there is a critical need for effective antiviral strategies. In this study, we report a unique antiviral platform, through computational design of ACE2-derived peptides which both target the viral spike protein receptor binding domain (RBD) and recruit E3 ubiquitin ligases for subsequent intracellular degradation of SARS-CoV-2 in the proteasome. Our engineered peptide fusions demonstrate robust RBD degradation capabilities in human cells and are capable of inhibiting infection-competent viral production, thus prompting their further experimental characterization and therapeutic development.

scholarly journals Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome

2012 ◽  
Vol 11 (12) ◽  
pp. 1405-1413 ◽  
Author(s):  
Shibo Jiang ◽  
Maria Elena Bottazzi ◽  
Lanying Du ◽  
Sara Lustigman ◽  
Chien-Te Kent Tseng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Protein Receptor

scholarly journals Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain

2009 ◽  
Vol 388 (4) ◽  
pp. 815-823 ◽  
Author(s):  
John E. Pak ◽  
Chetna Sharon ◽  
Malathy Satkunarajah ◽  
Thierry C. Auperin ◽  
Cheryl M. Cameron ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Immune Recognition ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Protein Receptor ◽  
Structural Insights

scholarly journals Targeted Intracellular Degradation of SARS-CoV-2 via Computationally-Optimized Peptide Fusions

2020 ◽  
Author(s):  
Pranam Chatterjee ◽  
Manvitha Ponnapati ◽  
Christian Kramme ◽  
Alex Plesa ◽  
Joseph Jacobson ◽  
...  
Keyword(s):  
Computational Design ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Experimental Characterization ◽  
Viral Production ◽  
Health Crisis ◽  
Intracellular Degradation ◽  
Protein Receptor ◽  
Therapeutic Development ◽  
Novel Coronavirus

Abstract The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has elicited a global health crisis of catastrophic proportions. With no approved cure or vaccine currently available, there is a critical need for effective antiviral strategies. In this study, we report a novel antiviral platform, through computational design of ACE2-derived peptides which both target the viral spike protein receptor binding domain (RBD) and recruit E3 ubiquitin ligases for subsequent intracellular degradation of SARS-CoV-2 in the proteasome. Our engineered peptide fusions demonstrate robust RBD degradation capabilities in human cells and are capable of inhibiting infection-competent viral production, thus prompting their further experimental characterization and therapeutic development.

scholarly journals Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Seth J. Zost ◽  
Pavlo Gilchuk ◽  
Rita E. Chen ◽  
James Brett Case ◽  
Joseph X. Reidy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cross Reactivity ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Human Monoclonal Antibodies ◽  
S Protein ◽  
Global Pandemic ◽  
Antibody Discovery ◽  
Novel Coronavirus ◽  
Rapid Antibody

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.

scholarly journals S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit

2020 ◽  
Author(s):  
Phuong Nguyen-Contant ◽  
A. Karim Embong ◽  
Preshetha Kanagaiah ◽  
Francisco A. Chaves ◽  
Hongmei Yang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Receptor Binding ◽  
Memory B Cells ◽  
Binding Domain ◽  
The Novel ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Cell Immunity ◽  
Antibody Levels

ABSTRACTThe high susceptibility of humans to SARS-CoV-2 infection, the cause of COVID-19, reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and PBMCs from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 in convalescent subjects were higher than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.IMPORTANCERecent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key questions are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and post-infection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study also suggests that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.

scholarly journals Genome Characterization and Potential Risk Assessment of the Novel SARS-CoV-2 Variant Omicron (B.1.1.529)

Zoonoses ◽  
2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Si Qin ◽  
Mengnan Cui ◽  
Siqi Sun ◽  
Jiyang Zhou ◽  
Zongmin Du ◽  
...  
Keyword(s):  
Sharp Increase ◽  
World Health ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Global Epidemic ◽  
New Variant ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Global Population

As the novel coronavirus SARS-CoV-2 spread around the world, multiple waves of variants emerged, thus leading to local or global population shifts during the pandemic. A new variant named Omicron (PANGO lineage B.1.1.529), which was first discovered in southern Africa, has recently been proposed by the World Health Organization to be a Variant of Concern. This variant carries an unusually large number of mutations, particularly on the spike protein and receptor binding domain, in contrast to other known major variants. Some mutation sites are associated with enhanced viral transmission, infectivity, and pathogenicity, thus enabling the virus to evade the immune protective barrier. Given that the emergence of the Omicron variant was accompanied by a sharp increase in infection cases in South Africa, the variant has the potential to trigger a new global epidemic peak. Therefore, continual attention and a rapid response are required to decrease the possible risks to public health.

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