Mutational landscape and in silico structure models of SARS-CoV-2 Spike Receptor Binding Domain reveal key molecular determinants for virus-host interaction

  title={Mutational landscape and in silico structure models of SARS-CoV-2 Spike Receptor Binding Domain reveal key molecular determinants for virus-host interaction},
  author={Shijulal Nelson-Sathi and PK Umasankar and Easwaran Sreekumar and Radeep Krishna Radhakrishnan Nair and Iype Joseph and Sai Ravi Chandra Nori and Jamiema Sara Philip and Roshny Prasad and K. S. Navyasree and Shikha Ramesh and Heera R. Pillai and Sanu Ghosh and TR Santosh Kumar and Madhavan Radhakrishna Pillai},
Protein-protein interactions between virus and host are crucial for infection. SARS-CoV-2, the causative agent of COVID-19 pandemic is an RNA virus prone to mutations. Formation of a stable binding interface between the Spike (S) protein Receptor Binding Domain (RBD) of SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) of host actuates viral entry. Yet, how this binding interface evolves as virus acquires mutations during pandemic remains elusive. Here, using a high fidelity bioinformatics… Expand
2 Citations
A computational approach to evaluate the combined effect of SARS-CoV-2 RBD mutations and ACE2 receptor genetic variants on infectivity: The COVID-19 host-pathogen nexus
It is inferred that it is important to consider both ACE2 variants and circulating SARS-CoV-2 RBD mutations to assess the stability of the virus-receptor association and evaluate infectivity. Expand
SARS-CoV-2 RBD mutations, ACE2 genetic polymorphism, and stability of the virus-receptor complex: The COVID-19 host-pathogen nexus.
It is inferred that it is important to consider both ACE2 genetic variants and Sars-CoV-2 RBD mutations to assess the stability of the virus-receptor association and evaluate the infectivity of circulating SARS-Co V-2. Expand


Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues. Expand
Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions
Analysis of the dynamic trajectories reveals that the binding interface consists of a primarily hydrophobic region and a delicate hydrogen-bonding network in the 2019 novel coronavirus. Expand
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans. Expand
Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase
The molecular basis of SARS-CoV-2 RNA replication is examined by determining the cryo-EM structures of the stalled pre-/post- translocated polymerase complexes and the inhibition mechanisms of the triphosphate metabolite of remdesivir are investigated through structural and kinetic analyses. Expand
Broad and Differential Animal Angiotensin-Converting Enzyme 2 Receptor Usage by SARS-CoV-2
Examination of receptor activity of 14 ACE2 orthologs found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells and have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models. Expand
Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus
These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019- nCoV. Expand
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry. Expand
Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV
It is shown that the SARS-CoV-2 spike protein is less stable than that of SARS -CoV, and limited cross-neutralization activities between SARS and COVID-19 patients’ sera showlimited cross- neutralization activities, suggesting that recovery from one infection might not protect against the other. Expand
Mining of epitopes on spike protein of SARS-CoV-2 from COVID-19 patients
This study analysed the correlation between Sor Nucleocapsid (N) protein-specific antibody levels and neutralizing antibody tires and identified a very strong correlation between antiRBD IgG titres and MN activity in recovered patients, which suggests that manipulating the RBD-induced immune responses might have the potential to be used in developing more effective COVID-19 vaccines. Expand
The spike protein of SARS-CoV — a target for vaccine and therapeutic development
Recent advances in the development of vaccines and therapeutics based on the S protein are highlighted, which plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. Expand