COVID-19 Pandemic: Insights into Structure, Function, and hACE2 Receptor Recognition by the SARS-CoV-2

Mittal, Anshumali; Manjunath, Kavyashree; Ranjan, Rajesh Kumar; Kaushik, Sandeep; Kumar, Sujeet; Verma, Vikash

doi:10.20944/preprints202005.0260.v1

Cited by 40 publications

(65 citation statements)

References 71 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus belonging to the Betacoronaviridae family ( 4 ). It has a spherical shape of 60-140nm in diameter with characteristic club-shaped spikes on the outer surface of the virion ( 1 , 4 ). This solar corona appearance led to the name coronavirus ( 1 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…It has a spherical shape of 60-140nm in diameter with characteristic club-shaped spikes on the outer surface of the virion ( 1 , 4 ). This solar corona appearance led to the name coronavirus ( 1 , 4 ). The SARS-CoV-2 genome sequence comprises the following: non-coding 5’-untranslated region (UTR)-replicase gene (ORF1ab), structural proteins (spike, envelope, membrane and nucleocapsid), accessory proteins (ORF6, 7ab, 8 and 9b) and non-coding 3’-UTR ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

2021

View full text Add to dashboard Cite

The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to respiratory failure and multi-organ failure or death. The pathogenesis of SARS-CoV-2 infection is attributed to a complex interplay between virus and host immune response. It involves activation of multiple inflammatory pathways leading to hyperinflammation and cytokine storm, resulting in tissue damage, acute respiratory distress syndrome (ARDS) and multi-organ failure. Accumulating evidence has raised concern over the long-term health effects of COVID-19. Importantly, the neuroinvasive potential of SARS-CoV-2 may have devastating consequences in the brain. This review provides a conceptual framework on how the virus tricks the host immune system to induce infection and cause severe disease. We also explore the key differences between mild and severe COVID-19 and its short- and long-term effects, particularly on the human brain.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

2021

View full text Add to dashboard Cite

show abstract

“…Moreover, given that many of the SARS-CoV-2 neutralizing epitopes are located in the viral receptor binding domain (RBD) of the Spike (S) protein (21)(22)(23)(24)(25)(26)(27)(28)(29), it is important to evaluate the relationship between RBD-specific IgG titers and neutralizing antibody responses.…”

Section: Introductionmentioning

confidence: 99%

Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

Nayak¹,

Gottimukkala²,

Kumar³

et al. 2020

Preprint

View full text Add to dashboard Cite

India is one of the countries most affected by the recent COVID-19 pandemic. Characterization of humoral responses to SARS-CoV-2 infection, including immunoglobulin isotype usage, neutralizing activity and memory B cell generation, is necessary to provide critical insights on the formation of immune memory in Indian subjects. In this study, we evaluated SARS-CoV-2 receptor-binding domain (RBD)-specific IgG, IgM, and IgA antibody responses, neutralization of live virus, and RBD-specific memory B cell responses in pre-pandemic healthy versus convalescent COVID-19 individuals from India. We observed substantial heterogeneity in the formation of humoral and B cell memory post COVID-19 recovery. While a vast majority (38/42, 90.47%) of COVID-19 recovered individuals developed SARS-CoV-2 RBD-specific IgG responses, only half of them had appreciable neutralizing antibody titers. RBD-specific IgG titers correlated with these neutralizing antibody titers as well as with RBD-specific memory B cell frequencies. In contrast, IgG titers measured against SARS-CoV-2 whole virus preparation, which includes responses to additional viral proteins besides RBD, did not show robust correlation. Our results suggest that assessing RBD-specific IgG titers can serve as a surrogate assay to determine the neutralizing antibody response. These observations have timely implications for identifying potential plasma therapy donors based on RBD-specific IgG in resource-limited settings where routine performance of neutralization assays remains a challenge.ImportanceOur study provides an understanding of SARS-CoV-2-specific neutralizing antibodies, binding antibodies and memory B cells in COVID-19 convalescent subjects from India. Our study highlights that PCR-confirmed convalescent COVID-19 individuals develop SARS-CoV-2 RBD-specific IgG antibodies, which correlate strongly with their neutralizing antibody titers. RBD-specific IgG titers, thus, can serve as a valuable surrogate measurement for neutralizing antibody responses. These finding have timely significance for selection of appropriate individuals as donors for plasma intervention strategies, as well as determining vaccine efficacy.

show abstract

“…Arrows indicate the critical binding residues for interaction between RBD and receptor, stars indicate Five of these six amino acids differ between SARS‐CoV‐2 and SARS‐CoV that are critical for hACE2 binding; dots indicate a four‐residue motif that allows the ridge to become more compact and allow better contacts with hACE2; triangle marks virus‐binding hotspots that lead to considerable stabilization of binding and higher affinity for ACE2. (B) Crystal structures of the SARS‐CoV‐2 RBD (core in green and RBM in blue) with the receptor ACE2 (in yellow) (PDB: 6LZG) 34 ; (C) Structural similarity of the RBD‐hACE2 complex between SARS‐CoV‐2 (green) (PDB: 6LZG) and SARS‐CoV (yellow) (PDB: 2AJF) 34 . These data that support the findings of this study are openly available in (PDB) at ( https://www1.rcsb.org/) 34 …”

Section: Molecular Characteristics Of the Sars‐cov‐2 Spike(s) Proteinmentioning

confidence: 99%

“…(B) Crystal structures of the SARS‐CoV‐2 RBD (core in green and RBM in blue) with the receptor ACE2 (in yellow) (PDB: 6LZG) 34 ; (C) Structural similarity of the RBD‐hACE2 complex between SARS‐CoV‐2 (green) (PDB: 6LZG) and SARS‐CoV (yellow) (PDB: 2AJF) 34 . These data that support the findings of this study are openly available in (PDB) at ( https://www1.rcsb.org/) 34 …”

Section: Molecular Characteristics Of the Sars‐cov‐2 Spike(s) Proteinmentioning

confidence: 99%

Molecular biology of the SARs‐CoV‐2 spike protein: A review of current knowledge

Zhu

Yin

et al. 2021

Journal of Medical Virology

View full text Add to dashboard Cite

The global coronavirus disease 2019 (COVID‐19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has led to an unprecedented worldwide public health emergency. Despite the concerted efforts of the scientific field, by April 25, 2021, SARS‐CoV‐2 had spread to over 192 countries/regions, causing more than 146 million confirmed cases including 31 million deaths. For now, an established treatment for patients with COVID‐19 remains unavailable. The key to tackling this pandemic is to understand the mechanisms underlying its infectivity and pathogenicity. As a predominant focus, the coronavirus spike (S) protein is the key determinant of host range, infectivity, and pathogenesis. Thereby comprehensive understanding of the sophisticated structure of SARS‐CoV‐2 S protein may provide insights into possible intervention strategies to fight this ongoing global pandemic. Herein, we summarize the current knowledge of the molecular structural and functional features of SARS‐CoV‐2 S protein as well as recent updates on the cell entry mechanism of the SARS‐CoV‐2, paving the way for exploring more structure‐guided strategies against SARS‐CoV‐2.

show abstract

COVID-19 Pandemic: Insights into Structure, Function, and hACE2 Receptor Recognition by the SARS-CoV-2

Cited by 40 publications

References 71 publications

Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

Molecular biology of the SARs‐CoV‐2 spike protein: A review of current knowledge

Contact Info

Product

Resources

About