¿Qué predicciones computacionales de mutaciones de sars-cov-2 se han confirmado?

(What computational predictions of sars-cov-2 mutations have been confirmed?)

Primeras 5 respuestas:

Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV.

We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein.

These mutations lead to a significant decrease in the antigenicity of this epitope in the SARS-CoV-2 S protein.

Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes.

Comparative analyses between SARS-CoV and SARS-CoV-2 spike glycoprotein showed 77% similarity between them where the most diverse region was .

Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV.

... alanine scanning mutagenesis on the "hotspot" residues at protein-protein interfaces using relative free energy calculations. Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV. In addition, our free energy calculations provide insight into the infectious ability of viruses on ...

Ref: Computational Prediction of Mutational Effects on SARS-CoV-2 Binding by Relative Free Energy Calculations [bioRxiv, 2020]

We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein.

... RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. ...

Ref: Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity [Brief. bioinform, 2020]

These mutations lead to a significant decrease in the antigenicity of this epitope in the SARS-CoV-2 S protein.

... critical and conserved linear neutralization epitope (overlap with fusion peptide) around a sparsely glycosylated area. These mutations lead to a significant decrease in the antigenicity of this epitope in the SARS-CoV-2 S protein. In addition, 62 T-cell epitopes in the SARS-CoV-2 S protein were predicted in our study. ...

Ref: Immunoinformatic analysis of T-and B-cell epitopes for SARS-CoV-2 vaccine design [Vaccines, 2020]

Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes.

... amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important ...

Ref: Insights on cross-species transmission of SARS-CoV-2 from structural modeling [bioRxiv, 2020-06-05]

Comparative analyses between SARS-CoV and SARS-CoV-2 spike glycoprotein showed 77% similarity between them where the most diverse region was .

... that, this could also promote viruses to escape antiviral therapies targeting transmembrane protease TMPRSS2 (ClinicalTrials.gov, NCT04321096) which is well reported protease to cleave at S1/S2 of S glycoprotein [47] . Comparative analyses between SARS-CoV and SARS-CoV-2 spike glycoprotein showed 77% similarity between them where the most diverse region was . ...

Ref: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach [bioRxiv, 2020-04-11]

Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV

... alanine scanning mutagenesis on the “hotspot” residues at protein-protein interfaces using relative free energy calculations Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV In addition, our free energy calculations provide insight into the infectious ability of viruses on ...

Ref: Computational Prediction of Mutational Effects on the SARS-CoV-2 Binding by Relative Free Energy Calculations [bioRxiv, 2020]

A total of 18 354 mutations in S protein were analyzed,

... to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18 354 mutations in S protein were analyzed, and we discovered that most of these mutations could destabilize the entire S protein and ...

Ref: Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity [Brief. bioinform, 2020]

Comparisons of MD simulations in the WT and mutants revealed a significant de-stabilization effect of the mutations on RBD and HR1 domains.

... HR1 (912-984) have been studied to examine its role on the spike glycoprotein native structure. Comparisons of MD simulations in the WT and mutants revealed a significant de-stabilization effect of the mutations on RBD and HR1 domains. We have investigated the impact of mapped mutations on the stability of the spike glycoprotein, ...

Ref: Insights into the structural and dynamical changes of spike glycoprotein mutations associated with SARS-CoV-2 host receptor binding [J Biomol Struct Dyn, 2020]

we show that most likely future mutations will make SARS-CoV-2 more infectious.

... a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain, we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding free energy calculation, we predict that a few ...

Ref: Mutations Strengthened SARS-CoV-2 Infectivity [J Mol Biol, 2020]

each mutation in the identical sequences causes a sharp increase in Shannon entropy, and also to omit biases in collection time and location in Shannon entropy analysis.

... of SARS-CoV-2 to be used for developing the current strategies of diagnosis, and treatment platforms. each mutation in the identical sequences causes a sharp increase in Shannon entropy, and also to omit biases in collection time and location in Shannon entropy analysis. [38] In a recent study, ten hotspot mutations including D614G (23403A>G) on S, L84S (28144T>C) ...

Ref: Genetics and genomics of SARS-CoV-2: A review of the literature with the special focus on genetic diversity and SARS-CoV-2 genome detection [Genomics, 2020-09-30]

The observed mutations in HS binding motif (R682W and R685H) decreased the positive charge of the site and increased its hydrophobicity.

... furin cleavage site PRRARS has a composition that overlaps with the HS binding motif XBBXBX. The observed mutations in HS binding motif (R682W and R685H) decreased the positive charge of the site and increased its hydrophobicity. To understand if the growth advantage was due to the loss of HS binding site ...

Ref: SARS-CoV-2 Quasispecies Mediate Rapid Virus Evolution and Adaptation [bioRxiv, 2020-08-10]

We identified 72 point mutations and 5 deletions across the genomes of 44 clinical isolates,

... to identify peptide epitopes that would be broadly applicable in vaccine development efforts against SARS-CoV-2. We identified 72 point mutations and 5 deletions across the genomes of 44 clinical isolates, with the majority of mutations (n = 46) and deletions (n = 4) occurring in ...

Ref: Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome [Sci Rep, 2020-08-25]

Structural protein modeling confirmed that most of the nonsynonymous mutations in the nonstructural proteins were neutral (Figs.S5-S11).

... Structural protein modeling confirmed that most of the nonsynonymous mutations in the nonstructural proteins were neutral (Figs.S5-S11). Conversely, several nonsynonymous mutations in the spike protein might have functional consequences: notably, the G614 clade-defining mutation D614G is located in subdomain 1 (SD1; Fig.4, Fig.S5 ). In the trimeric ...

Ref: A genetic barcode of SARS-CoV-2 for monitoring global distribution of different clades during the COVID-19 pandemic [Int J Infect Dis, 2020-08-22]

The predicted structures proved to be accurate within the targeted RBD region when compared to experimentally derived structures published weeks later.

... we predicted (and publicly released) structures of the SARS-CoV-2 spike protein using homology-based structural modeling. The predicted structures proved to be accurate within the targeted RBD region when compared to experimentally derived structures published weeks later. Next we used our in silico design platform to iteratively propose mutations to SARS-CoV-1 neutralizing ...

Ref: Rapid in silico design of antibodies targeting SARS-CoV-2 using machine learning and supercomputing [bioRxiv, 2020-04-10]

The secondary structure prediction analysis of these seven mutations shows that three of them cause alteration in the structure of RdRp.

... between them. Our data revealed the occurrence of seven mutations in Indian isolates of SARS-CoV-2. The secondary structure prediction analysis of these seven mutations shows that three of them cause alteration in the structure of RdRp. Furthermore, we did protein modelling studies to show that these mutations can potentially alter the ...

Ref: Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure [PeerJ, 2020-07-03]

Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation.

... analyses of mutation were based on the nine structural and non-structural genes of SARS-CoV-2 strains. Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation. ResultsPhylogenetic analyses revealed the evolution of "genome-type clusters" and adaptive selection of "L" type SARS-CoV-2 ...

Ref: The novel Coronavirus enigma: Phylogeny and mutation analyses of SARS-CoV-2 viruses circulating in India during early 2020 [bioRxiv, 2020-05-26]

Table 6 presents the top mutations from the set of mutants predicted to lead to the largest increase in ΔΔG per site.

... equilibrium towards rhACE2-S-protein complex formation and reduce the dose required for inhibition of viral infection. Table 6 presents the top mutations from the set of mutants predicted to lead to the largest increase in ΔΔG per site. These mutations are excellent candidates to improve the efficacy of rhACE2 therapy in COVID-19. We ...

Ref: Missense variants in ACE2 are predicted to encourage and inhibit interaction with SARS-CoV-2 Spike and contribute to genetic risk in COVID-19 [bioRxiv, 2020-05-04]

Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential,

... compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the ...

Ref: Comparing the Binding Interactions in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV [J Phys Chem Lett, 2020]

Residue 364 Ala (A) of bat coronavirus BM48-31 is omitted.

... closely related species, including SARS-CoV [15] , bat coronavirus RaTG13 [40] , bat coronavirus BM48-31 [4] , and bat coronavirus CoVZC45 [9] . Detailed numbering is given according to SARS-CoV-2. Residue 364 Ala (A) of bat coronavirus BM48-31 is omitted. ...

Ref: Mutations Strengthened SARS-CoV-2 Infectivity [J Mol Biol, 2020-07-23]

The mutations at glycine residues G431, G648 and G35 residues have maximum destabilizing effects on the full-length S protein.

... the Table 1 according to the mean values of ΔΔG of mutations in each position. The mutations at glycine residues G431, G648 and G35 residues have maximum destabilizing effects on the full-length S protein. In contrast, the mutations at serine residues S514, S735 and S50 residues have induced highly ...

Ref: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity [bioRxiv, 2020-05-23]

Current predictions suggest that traditional vaccine strategies might be too slow to address the spread of the pandemic and mitigate the death toll 59 .

... Custommune approach. Our implementation of Custommune was here extended to include vaccine design for SARS-CoV-2. Current predictions suggest that traditional vaccine strategies might be too slow to address the spread of the pandemic and mitigate the death toll 59 . Furthermore, immune responses developed during natural infection might be insufficient to provide long-term protection against ...

Ref: Custommune: a web tool to design personalized and population-targeted vaccine epitopes [bioRxiv, 2020-04-29]

We predict the free energy changes following existing mutations using our TopNetTree model [44] .

... which are relevant to the binding of SARS-COV-2 S protein and antibody 4A8 (PDB: 7C2L). We predict the free energy changes following existing mutations using our TopNetTree model [44] . The RBD mutations are computed which are in the distance of 10Å to antibodies. Our ...

Ref: Prediction and mitigation of mutation threats to COVID-19 vaccines and antibody therapies [bioRxiv, 2020-10-13]

The top ranked docking results for both proteins show surprising associations with C3b at a common region between amino acid residues 771 -850.

... length as ORF8, as negative controls for modelling interactions with C3b ( Figure 4 ). The top ranked docking results for both proteins show surprising associations with C3b at a common region between amino acid residues 771 -850. The interacting regions appear to be located at an exterior surface, away from the ORF8/F1 ...

Ref: SARS-CoV-2 ORF8 can fold into human factor 1 catalytic domain binding site on complement C3b: Predict functional mimicry [bioRxiv, 2020-08-05]

In-silico saturation mutagenesis provides a fast methodology to investigate all possible mutations and identify the potential functional sites.

... map of SARS-CoV-2 S mutations still lacks for identifying the target sites for vaccine design. In-silico saturation mutagenesis provides a fast methodology to investigate all possible mutations and identify the potential functional sites. It has been applied to Mycobacterium research to determine the effects of missense mutations on ...

Ref: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity [bioRxiv, 2020-05-23]

Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures.

... affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. INTERPRETATION: One of the two mutations, likely developed within the genome during virus spread, could ...

Ref: Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy [J Infect, 2020]

We used structure-based energy calculations and sequence-based bioinformatics tools to quantify the systemic effects of missense mutations on the protein structure and function.

... all residues in the S and ACE2 proteins to all other 19 amino acid types. We used structure-based energy calculations and sequence-based bioinformatics tools to quantify the systemic effects of missense mutations on the protein structure and function. A total of 18,354 mutations in SARS-CoV-2 spike protein were analyzed and we discovered that ...

Ref: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity [bioRxiv, 2020-05-23]

We predict that mutations are more detrimental in ACE2 than TMPRSS2.

... data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results ...

Ref: SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals [bioRxiv, 2020-08-19]

We identify residues affecting the affinities of the two domains for hACE2.

... methods complexes of hACE2 with the receptor binding domains (RBDs) of viruses SARS-CoV-2 and SARS-CoV. We identify residues affecting the affinities of the two domains for hACE2. We also propose mutations at key SARS-CoV-2 positions, which might enhance hACE2 affinity. Such mutations ...

Ref: Computational optimization of the SARS-CoV-2 receptor-binding-motif affinity for human ACE2 [bioRxiv, 2020-07-20]

The effect of mutations of these major proteins were also investigated using various in silico approaches.

... Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly ...

Ref: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight [PLoS One, 2020]

Genome-wide annotations of a wider range of sequences (50-2500) revealed considerable number of mutations throughout the SARS-CoV-2 genome,

... and Malayan Pangolin sequences helped reveal key RBD mutations and the polybasic furin cleavage sites. Genome-wide annotations of a wider range of sequences (50-2500) revealed considerable number of mutations throughout the SARS-CoV-2 genome, which includes both mismatch and deletion mutations both in translated and untranslated regions. Moreover, the ...

Ref: Genomic diversity and evolution, diagnosis, prevention, and therapeutics of the pandemic COVID-19 disease [PeerJ, 2020-09-01]

No mutations were observed in non-allergenic and non-toxic T-cell epitopes from S, M and N protein.

... to 311 in N protein ( Supplementary Fig. 11) . Particularly, the epitopes without allergenicity and toxicity containing one functional residue (highly conserved and exposed) included B-cell Table 10 ). No mutations were observed in non-allergenic and non-toxic T-cell epitopes from S, M and N protein. ...

Ref: Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2 [Virus Res, 2020-07-01]

their stability and affinity binding to hACE2 (S19-D615) were calculated.

... better. 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 were simulated and their stability and affinity binding to hACE2 (S19-D615) were calculated. Our analysis indicates SARS-CoV-2 could infect humans from different populations with no preference, and a ...

Ref: Binding Ability Prediction between Spike Protein and Human ACE2 Reveals the Adaptive Strategy of SARS-CoV-2 in Humans [bioRxiv, 2020-06-25]

The secondary structure of the RNA-dependent RNA polymerase/nonstructural protein NSP12 was predicted with respect to the novel A97V mutation Results:

... of the coevolving mutations were done in comparison to the prototype SARS-CoV-2 from Wuhan, China The secondary structure of the RNA-dependent RNA polymerase/nonstructural protein NSP12 was predicted with respect to the novel A97V mutation Results: Phylogenetic analyses revealed the evolution of “genome-type clusters” and adaptive selection of “L”-type SARS-CoV-2 strains ...

Ref: The Novel Coronavirus Enigma: Phylogeny and Analyses of Coevolving Mutations Among the SARS-CoV-2 Viruses Circulating in India [JMIR Bioinformatics Biotechnol, 2020]

An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc

... an immunoadhesin form of human ACE2 (ACE2-Fc) Two of these mutations impaired neutralization of SARS-CoV-1 An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc These data narrow the potential SARS-CoV-2 reservoir, suggest that SARS-CoV-1 and -2 originate from distinct ...

Ref: Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 [JMIR Bioinformatics Biotechnol, 2020]

These results emphasized the possibility that new mutations have emerged in that area.

... identified imported cases of a novel D614A mutation in the spike glycoprotein of SARS-CoV-2 in the South Korea. SARS-CoV-2 harboring the novel mutation was isolated from returning travelers from Uzbekistan. These results emphasized the possibility that new mutations have emerged in that area. ...

Ref: Emergence of the D614A mutation in the spike protein of SARS-CoV-2: Imported cases to the South Korea [JMIR Bioinformatics Biotechnol, 2020-09-07]

Both the predictions and the 3D models reveal additional beta strands and hydrogen bonds.

... there are several mutations that may have strengthened the binding affinity of the surface glycoprotein. Both the predictions and the 3D models reveal additional beta strands and hydrogen bonds. These additional mutations may cause changes in structural conformations and cause a higher binding affinity. ...

Ref: A comparative analysis for SARS-CoV-2 [JMIR Bioinformatics Biotechnol, 2020-04-08]

three of four mutations that we identified as detrimental for RBD expression or ACE2 binding greatly reduced pseudovirus entry,

... observed for entry by the spike-pseudotyped lentiviral particles generally confirmed the deep mutational scanning measurements: three of four mutations that we identified as detrimental for RBD expression or ACE2 binding greatly reduced pseudovirus entry, while a mutation that had little phenotypic effect in the deep mutational scanning did not ...

Ref: Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding [bioRxiv, 2020-06-17]

It presents the change of energy of molecular structure and the difference in molecular interactions between wild-type and mutant-type alleles.

... We use COVID-3D (http://biosig.unimelb.edu.au/covid3d/), an online resource exploring the structural distribution of genetic variations of SARS-CoV-2, to predict the functional effects of mutations (24) . It presents the change of energy of molecular structure and the difference in molecular interactions between wild-type and mutant-type alleles. ...

Ref: Ongoing natural selection drives the evolution of SARS-CoV-2 genomes [bioRxiv, 2020-09-09]

These additional mutations may cause changes in structural conformations and cause a higher binding affinity.

... receptors, there are several mutations that may have strengthened the binding affinity of the surface glycoprotein. Both the predictions and the 3D models reveal additional beta strands and hydrogen bonds. These additional mutations may cause changes in structural conformations and cause a higher binding affinity. ...

Ref: A comparative analysis for SARS-CoV-2 [bioRxiv, 2020-04-08]

Additionally, our microsecond molecular dynamics simulations of mutant structures indicate relatively stable secondary structures.

... and/or the pseudoknot of the FSE, potentially dismantling the virus against translation of the polyproteins. Additionally, our microsecond molecular dynamics simulations of mutant structures indicate relatively stable secondary structures. These findings not only advance our computational design of RNAs containing pseudoknots; they pinpoint to ...

Ref: Structure-Altering Mutations of the SARS-CoV-2 Frame Shifting RNA Element [bioRxiv, 2020-08-30]

Our results of alanine scanning showed that all native to alanine mutations studied here disfavored binding.

... Our results of alanine scanning showed that all native to alanine mutations studied here disfavored binding. All mutations on SARS-CoV showed a mild to moderate effect, whereas three mutations, L455A, F456A, and Q493A on SARS-CoV-2 weakened the binding by over 2 kcal/mol. Furthermore, L455A and Q493A ...

Ref: Computational Prediction of Mutational Effects on SARS-CoV-2 Binding by Relative Free Energy Calculations [J Chem Inf Model, 2020-07-28]

We saw an average mutation rate of 1.37 × 10 −3 nucleotide substitution per site per year for SARS-CoV-2,

... the SNP analysis to estimate the mutation rate of the SARS-CoV-2 from these 10 patients. We saw an average mutation rate of 1.37 × 10 −3 nucleotide substitution per site per year for SARS-CoV-2, which is consistent with other reports on the mutation rate of SARS-CoV-2 (19, 24) and ...

Ref: Epidemiological and Genomic Analysis of SARS-CoV-2 in 10 Patients From a Mid-Sized City Outside of Hubei, China in the Early Phase of the COVID-19 Outbreak [Front Public Health, 2020-09-18]

it would not survive

... Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive It is expected that our results could provide an important clue in understanding the genomic ...

Ref: Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome [Osong Public Health Res Perspect, 2020]

Experiments show that S protein mutation D614G also has made SARS-CoV-2 more infectious [38] .

... is believed that these extra residues might change SARS-CoV-2"s behavior in ACE2 assisted entry of host cells [33] . However, this speculation has no qualitative nor quantitative validation at present. Experiments show that S protein mutation D614G also has made SARS-CoV-2 more infectious [38] . ...

Ref: Mutations Strengthened SARS-CoV-2 Infectivity [J Mol Biol, 2020-07-23]

63 predictions after computational alanine scanning mutagenesis of ACE2-RBD interface residues.

... in genome-wide studies, 39 mutants with reported effects on the recognition of the RBD, and 63 predictions after computational alanine scanning mutagenesis of ACE2-RBD interface residues. This dataset will help accelerate the design of therapeutics against SARS-CoV-2, as well as contribute ...

Ref: Structural models of human ACE2 variants with SARS-CoV-2 Spike protein for structure-based drug design [Sci Data, 2020]

23 point mutations were predicted to significantly influence the affinity and stability of the spike protein (Fig. 5) ,

... all mutationson the S gene and their binding capacity with ACE2 receptor in human beings. 23 point mutations were predicted to significantly influence the affinity and stability of the spike protein (Fig. 5) , among which 9 polymorphisms exhibited increased affinity and stability while 14 ones showed decreased affinity ...

Ref: Binding Ability Prediction between Spike Protein and Human ACE2 Reveals the Adaptive Strategy of SARS-CoV-2 in Humans [bioRxiv, 2020-06-25]

We confirmed that mutations in different genomic regions of SARS-CoV-2 have specific influence on virus reproductive adaptability,

... regions including the envelop, membrane, nucleocapsid, and spike glycoproteins to become a novel infectious agent. We confirmed that mutations in different genomic regions of SARS-CoV-2 have specific influence on virus reproductive adaptability, allowing for genotype adjustment and adaptations in rapidly changing environments. Moreover, for the first time ...

Ref: Evolutionary Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2 [Pathogens, 2020-03-23]

Vibrational entropy changes were predicted for both wild type and mutant 108 proteins for evaluating the impact of mutations on conformation, flexibility and stability of 109 proteins.

... a 106 positive or negative log-odds value represents co-occurring and mutually exclusive mutations, 107 respectively. Vibrational entropy changes were predicted for both wild type and mutant 108 proteins for evaluating the impact of mutations on conformation, flexibility and stability of 109 proteins. The SARS-CoV-2 proteome can be classified into ORF1a, ORF1b (or ORF1ab joint), They were also ...

Ref: Mutational signatures in countries affected by SARS-CoV-2: Implications in host-pathogen interactome [bioRxiv, 2020-09-17]

fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome;

... been observed;only 169 mutations (5 27%) had a prevalence greater than 1% of genomes Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three ...

Ref: Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the “Confined Virus”? [Pathogens, 2020]

Computational alanine scanning mutagenesis was performed to predict changes in Gibbs’ free energy

... ‘hot-spot’ residues in a positive control PPI (PMI / MDM2) and the CoV-2 RBD/ACE2 complex. Computational alanine scanning mutagenesis was performed to predict changes in Gibbs’ free energy that are associated with mutating residues at the positive control (PMI/MDM2) or SARS RBD/ACE2 binding ...

Ref: Computational Hot-Spot Analysis of the SARS-CoV-2 Receptor Binding Domain / ACE2 Complex [bioRxiv, 2020-08-06]

hydrophobic contacts in the complex of the SARS-CoV-neutralizing antibody 80R are disrupted in the SARS-CoV-2 homology complex model,

... toward a more tilted binding groove in the complex in comparison with the SARS-CoV complex. On the other hand, hydrophobic contacts in the complex of the SARS-CoV-neutralizing antibody 80R are disrupted in the SARS-CoV-2 homology complex model, which is attributed to failure of recognition of SARS-CoV-2 by 80R. ...

Ref: cord_uid b0cf3viw Enhanced receptor binding of SARS-CoV-2 throug... b0cf3viw Enhanced receptor binding of SARS-CoV-2 throug... Name: title, dtype: object [bioRxiv, cord_uid b0cf3viw 2020 b0cf3viw 2020 Name: publish_time, dtype: object]

From Figure 6 , a slightly increasing trend of binding free energy is observed such that the largest change is positive while the second largest change is negative.

... From Figure 6 , a slightly increasing trend of binding free energy is observed such that the largest change is positive while the second largest change is negative. Notice that mutation S477N is observed increasing of its frequency in Figure 3 . Interestingly, mutation T478I changes from amino acid with polar uncharged side chains, Threonine, to an amino ...

Ref: Mutations Strengthened SARS-CoV-2 Infectivity [J Mol Biol, 2020-07-23]

indicating that the N gene is one of the most non-conservative genes in the SARS-CoV-2 genome.

... mutated unevenly, we have computed the mutation rate and mutation h-index of all SARS-CoV-2 genes, indicating that the N gene is one of the most non-conservative genes in the SARS-CoV-2 genome. We show that due to human immune response induced APOBEC mRNA (Câ¯>â¯T) editing, diagnostic targets ...

Ref: Mutations on COVID-19 diagnostic targets [Genomics, 2020]

Mutations in the phosphorylation sites of SARS-CoV-2 encoded nucleocapsid protein isolated from various populations and locations, are described.

... the origin, evolution and biochemistry (molecular biology) of SARS-CoV-2 is a prerequisite to its control. Mutations in the phosphorylation sites of SARS-CoV-2 encoded nucleocapsid protein isolated from various populations and locations, are described. Mutations occurred in the phosphorylation sites, all located within a stretch which forms a phosphorylation ...

Ref: Mutations in the phosphorylation sites of SARS-CoV-2 encoded nucleocapsid protein and structure model of sequestration by protein 14-3-3 [Biochem Biophys Res Commun, 2020]

We identified 64 point mutations and 4 deletions 175 across the genomes of 44 clinical isolates,

... identify peptide epitopes that would be broadly applicable 174 in vaccine development efforts against SARS-CoV-2. We identified 64 point mutations and 4 deletions 175 across the genomes of 44 clinical isolates, with all deletions and the majority of mutations (n=45) 176 occurring in the ORF1ab polyprotein ...

Ref: Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome [bioRxiv, 2020-05-14]

polar residue mutations results in greater electrostatic complementarity than that of the SARS-CoV complex.

... in SARS-CoV-2 creates a salt bridge across the central hydrophobic contact region, which along with polar residue mutations results in greater electrostatic complementarity than that of the SARS-CoV complex. Furthermore, both electrostatic effects and enhanced hydrophobic packing due to removal of four out of ...

Despite amino acid mutations in these regions in both proteins, the structures are highly superimposable.

... were identified and highlighted in the pairwise sequence alignment of RBD ( Figure 2B ). Despite amino acid mutations in these regions in both proteins, the structures are highly superimposable. The location corresponding to the deletions of the two sequence regions in bat SARS CoV ...

Ref: Evolutionary relationships and sequence‐structure determinants in human SARS coronavirus‐2 spike proteins for host receptor recognition [Proteins, 2020-06-16]

An in silico mutational study suggests a higher affinity of the SARS-Cov-2 spike protein favorable to the human ACE2 receptor,

... domain (Rabaan et al. 2020 ). These domains are guiding the link to host receptors. An in silico mutational study suggests a higher affinity of the SARS-Cov-2 spike protein favorable to the human ACE2 receptor, compared to the Bat-CoV spike protein Ortega et al. 2020) . The N82 in ACE2 ...

Ref: Genomics insights of SARS-CoV-2 (COVID-19) into target-based drug discovery [Med Chem Res, 2020-07-31]

For the C-to-U mutations, the context of the upstream uracil and downstream guanine from mutated position was found to be most prevalent.

... We also found the point mutations which are consistent with other RNA editing enzymes, ADARs. For the C-to-U mutations, the context of the upstream uracil and downstream guanine from mutated position was found to be most prevalent. Further, the degree of increase of U in SARS-CoV-2 variants correlates with enhanced production of ...

Ref: Point mutation bias in SARS-CoV-2 variants results in increased ability to stimulate inflammatory responses [Sci Rep, 2020-10-20]

T1103P mutation in Nsp3 was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type;

... that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting ...

Ref: Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2 [bioRxiv, 2020-06-20]

ORF8 protein had the highest mutation density across all geographical areas.

... spike D614G was the most common, occurring mostly in genomes outside China and United States. ORF8 protein had the highest mutation density across all geographical areas. Moreover, mutation hotspots neighboring and at the catalytic site of RNA-dependent RNA polymerase were found ...

Ref: Genomic and proteomic mutation landscapes of SARS-CoV-2 [J. med. virol, 2020]

Some mutations that break hydrogen bonds and/or salt bridges in antibody−antigen interactions will have a large impact.

... there are many mutations on the S proteins. The RBD is also prone to mutations. Some mutations that break hydrogen bonds and/or salt bridges in antibody−antigen interactions will have a large impact. However, silent mutations, such as those that replace hydrophobic residues with other hydrophobic residues, will ...

Ref: Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine [J Chem Inf Model, 2020-06-12]

The computational search will provide libraries
of optimized therapeutics capable of reducing the SARS-CoV-2 infection on a global scale.

... free energies. In this adaptive evolution, atomistic molecular dynamics simulations of the template-RBD complexes are iteratively perturbed by the peptide mutations, which are retained under favorable Monte Carlo decisions. The computational search will provide libraries
of optimized therapeutics capable of reducing the SARS-CoV-2 infection on a global scale.
...

Ref: Adaptive Evolution of Peptide Inhibitors for Mutating SARS-CoV-2 [ChemRxiv, 2020-07-10]

The mutation of C14408T at NSP12 in Indian isolates of SARS-CoV-2 lead to the substitution of proline with threonine.

... with the cofactors NSP7 and NSP8 to form the RNA dependent RNA polymerase (RdRP) complex. The mutation of C14408T at NSP12 in Indian isolates of SARS-CoV-2 lead to the substitution of proline with threonine. The proline residue at position 323 corresponding to the polyprotein results in an unusual turn ...

Ref: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype [bioRxiv, 2020-06-07]

We found rare variants that would result in missense mutations in 7 out of the 25 binding residues (Dataset S2) .

... potential differences in binding to SARS-CoV-2 S and their relationship to selected and accelerated sites. We found rare variants that would result in missense mutations in 7 out of the 25 binding residues (Dataset S2) . Some of those (e.g. E35K with an AF of 0.00001636) could reduce the virus binding ...

Ref: Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates [bioRxiv, 2020-04-18]

Our analysis revealed three unique linked mutations, which are prevalent in most of the sequences studied.

... of SARS-CoV-2 from the western part of India, the worst affected region by the pandemic. Our analysis revealed three unique linked mutations, which are prevalent in most of the sequences studied. These may serve as a molecular marker to track the spread of this viral variant ...

Ref: Phylogenomic analysis of SARS-CoV-2 genomes from western India reveals unique linked mutations [bioRxiv, 2020-08-04]

The top RBD residues and mutations with maximum and minimum ΔΔG values are shown in Table 1 and Figure 2B .

... and analyzed a total of 3,705 mutations generated from 195 residues of its RBD chain. The top RBD residues and mutations with maximum and minimum ΔΔG values are shown in Table 1 and Figure 2B . The average change in protein stability at each SARS-CoV-2 S residue position ranged from 26.266 ...

Ref: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity [bioRxiv, 2020-05-23]

Next, we computed the binding affinities of the RBD designs with ACE2 obtained from Rosetta simulations.

... Next, we computed the binding affinities of the RBD designs with ACE2 obtained from Rosetta simulations. We found that the binding affinities ranged from -8.8 kcal/mol to -12.5 kcal/mol across the designs (Figure 4 ). When the binding affinities were compared, many of the designs scored ...

Ref: High Throughput Designing and Mutational Mapping of RBD-ACE2 Interface Guide Non-Conventional Therapeutic Strategies for COVID-19 [bioRxiv, 2020-05-19]

computational alanine scanning with BAlaS predicted seven residues on each protein, which when mutated, significantly alter binding energy.

... five residues each on ACE2 and SARS-CoV-2 RBD that are predicted to stabilize the complex; computational alanine scanning with BAlaS predicted seven residues on each protein, which when mutated, significantly alter binding energy. There is good agreement between the two methods; both servers predicted ACE2 residues H34, D38, ...

Ref: Computational Hot-Spot Analysis of the SARS-CoV-2 Receptor Binding Domain / ACE2 Complex [bioRxiv, 2020-08-06]

A one-base deletion caused a frame-shift mutation in ORF10 of ZXC21 ( Fig. S1 ).

... protein sequence of SARS-CoV-2 ORF8 shared very low similarity with sequences in SARS-CoV and BM48-31, and ORF10 had a premature stop codon in both SARS-CoV and BM48-31 (Fig. S1) . A one-base deletion caused a frame-shift mutation in ORF10 of ZXC21 ( Fig. S1 ). ...

Ref: On the origin and continuing evolution of SARS-CoV-2 [Natl Sci Rev, 2020-03-03]

We also identified 11 residues with high aa mutation frequency, and each contains four types of aa variations.

... amino acid (aa). An outlier strain (EPI_ISL_463893) from Bosnia and Herzegovina possessed six aa substitutions. We also identified 11 residues with high aa mutation frequency, and each contains four types of aa variations. The infamous D614G variant has spread worldwide with ever-rising dominance and across regions with different ...

Ref: Comprehensive annotations of the mutational spectra of SARS-CoV-2 spike protein: a fast and accurate pipeline [Transbound. emerg. dis. (Internet), 2020]

The amino acidic position 614 (mutation D -G) has been found most frequently mutated in the sequences of our subset (Table S2) .

Ref: Selective pressure on SARS-CoV-2 protein coding genes and glycosylation site prediction [Heliyon, 2020-09-21]

The next three top US SARS-CoV-2 mutations were first detected in the US

... first detected in China (2 cases), Singapore (2 cases), and the United Kingdom (1 case) The next three top US SARS-CoV-2 mutations were first detected in the US These eight top mutations belong to two disconnected groups The first group consisting of 5 ...

Ref: Characterizing SARS-CoV-2 mutations in the United States [Research square, 2020]

The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection.

... RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation ...

Ref: Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13 [bioRxiv, 2020-03-02]

in-silico Ala-scanning and long-timescale MD simulations,

... as any vaccine design endeavors since these mutations could act as antibody escape mutants Furthermore, in-silico Ala-scanning and long-timescale MD simulations, highlight the crucial role of the residues at the interface of RBD and ACE2 that ...

Ref: Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations [bioRxiv, 2020]

The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein

... S-protein apo structure, S-protein–furin complex structure, and the free binding energy of the complex Results The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: −0 086 kcal/mol) The mutation resulted in a stronger binding affinity (Kd = 1 ...

Ref: Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity [International Journal of Infectious Diseases, 2020]

We generated predictions for 15,295 mutations in human ACE2 and 24,187 mutations in SARS-Cov-2 full-length S

... the mutation pathogenicity of all mutations of S and ACE2 proteins based their protein sequences. We generated predictions for 15,295 mutations in human ACE2 and 24,187 mutations in SARS-Cov-2 full-length S including 4,237 mutations in its RBD region. As shown in Figure 4A Protein destabilization is ...

Ref: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity [bioRxiv, 2020-05-23]

Most studies simply considered the number of residues mutated relative to human ACE2 32,57−59 ,

... protein structure of the S-protein:ACE2 complex to computationally predict the breadth of possible viral hosts. Most studies simply considered the number of residues mutated relative to human ACE2 32,57−59 , although some also analyse the effect that these mutations have on the interface stability 34, ...

Ref: SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals [Sci Rep, 2020-10-05]

Several reports have documented mutations in several SARS-CoV-2 encoded proteins,

... Several reports have documented mutations in several SARS-CoV-2 encoded proteins, in particular the Spike protein [7] which determines the infectivity of SARS-CoV-2 by binding to ACE2 [8, 9] . Other reports have described mutations in other proteins encoded by SARS-CoV-2, ...

Ref: Mutations in the phosphorylation sites of SARS-CoV-2 encoded nucleocapsid protein and structure model of sequestration by protein 14-3-3 [Biochem Biophys Res Commun, 2020-08-15]

The computational search will provide librariesof optimized therapeutics capable of reducing the SARS-CoV-2 infection on a global scale. .

... RBD-binding free energies. In this adaptive evolution, atomistic molecular dynamics simulations of the template-RBD complexes are iteratively perturbed by the peptide mutations, which are retained under favorable Monte Carlo decisions. The computational search will provide librariesof optimized therapeutics capable of reducing the SARS-CoV-2 infection on a global scale. . ...

Ref: Adaptive Evolution of Peptide Inhibitors for Mutating SARS-CoV-2. [ChemRxiv : the preprint server for chemistry, 2020-07-10]

Peptide stability, mutation analysis, toxicity, allergenicity, hydro and physiochemical features were calculated and the results were presented in Supplementary Table 6 .

... Peptide stability, mutation analysis, toxicity, allergenicity, hydro and physiochemical features were calculated and the results were presented in Supplementary Table 6 . While no peptide listed is toxic, a majority of them are potentially allergenic. To forecast the probability of an immune response induced by the predicted HLA-1 binding peptides, the class ...

Ref: Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2 [Infect Dis Poverty, 2020-07-10]

Consequent alterations of miRNA binding and structure were also predicted for these mutations.

... correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S D domain) and G1124V (in ...

Ref: Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility [J. Biosci., 2020]

SNVs 124 could impact assay accuracy if diagnostic primers and probes are also being used to quantify 125 viral loads in patients.

... primer ( Figure 3A) . As the authors of the preprint, Vanaerschot et al., noted, SNVs 124 could impact assay accuracy if diagnostic primers and probes are also being used to quantify 125 viral loads in patients. We found that at least ten other primer pairs could potentially be at risk in ...

Ref: COVID-19 CG: Tracking SARS-CoV-2 mutations by locations and dates of interest [bioRxiv, 2020-09-28]

From the top five mutations at 0.1% frequency, we performed MHC class 1 binding prediction with NetMHC4 [15] ,

... we explored whether these RBD mutations were influencing the class 1 presentation of SARS-CoV-2 epitopes. From the top five mutations at 0.1% frequency, we performed MHC class 1 binding prediction with NetMHC4 [15] , for both the wild-type (Wuhan strain) and the mutated strain, choosing the most frequent HLAs ...

Ref: Companion vaccine Bioinformatic design tool reveals limited functional genomic variability of SARS-Cov-2 Spike Receptor Binding Domain [bioRxiv, 2020-06-22]

Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2.

... emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the ...

Ref: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 [Infect Genet Evol, 2020]

Although SARS-CoV-1 and SARS-CoV-2 share the sequence similarity with 80% homolog.

... Although SARS-CoV-1 and SARS-CoV-2 share the sequence similarity with 80% homolog. After performing the alignment, they reveal their 75% similarity in spike protein. The S protein mediates viral entry into host cells by first binding to a host receptor through the ...

Ref: Genomic variance of Open Reading Frames (ORFs) and Spike protein in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [J Chin Med Assoc, 2020-07-17]

Some of these mutations are predicted to have impact on viral and host factors, which might affect transmission and disease severity.

... in the important regions of the viral genome including Spike, RdRP and nucleocapsid coding genes. Some of these mutations are predicted to have impact on viral and host factors, which might affect transmission and disease severity. This preliminary evidence of emergence of multiple subclones of SARS-CoV-2, which might have altered phenotypes, ...

We further evaluated the potential of these frequently mutated residues in protein structure stability of spike glycoprotein and their possible functional consequences in other proteins.

... residues by aligning ~660 SARS-CoV-2 genomes and validated in 10,000 datasets available in GISAID Nextstrain. We further evaluated the potential of these frequently mutated residues in protein structure stability of spike glycoprotein and their possible functional consequences in other proteins. Among the 11 genes, surface glycoprotein, nucleocapsid, ORF1ab, and ORF8 showed frequent mutations, while envelop, ...

Ref: Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission [Infect Genet Evol, 2020]

Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history.

... we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously ...

Ref: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity [bioRxiv, 2020-04-11]

atomistic molecular dynamics simulations of the template-RBD complexes are iteratively perturbed by the peptide mutations, which are retained under favorable Monte Carlo decisions.

... mutations, while retaining those mutations that maximize their RBD-binding free energies. In this adaptive evolution, atomistic molecular dynamics simulations of the template-RBD complexes are iteratively perturbed by the peptide mutations, which are retained under favorable Monte Carlo decisions. The computational search will provide librariesof optimized therapeutics capable of reducing the SARS-CoV-2 infection on ...

Ref: Adaptive Evolution of Peptide Inhibitors for Mutating SARS-CoV-2. [ChemRxiv : the preprint server for chemistry, 2020-07-10]

We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants.

... We then utilize our previously developed protein design tool, Eris, to predict thermodynamically stabilizing mutations in proteins. We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants. We finally utilize the pipeline to identify new prefusion spike protein stabilization mutants. ...

Ref: Prefusion spike protein stabilization through computational mutagenesis [bioRxiv, 2020-06-19]

A total of 22 predicted N-glycosylation positions were found in the SARS-CoV-2 surface glycoprotein;

... pressure was identified in nsp2, nsp3, nsp4, nsp6, nsp12, helicase, ORF3a, ORF8, and N sub-sets. A total of 22 predicted N-glycosylation positions were found in the SARS-CoV-2 surface glycoprotein; one of them, 343N, was located within the RBD. One predicted N-glycosylation site was found ...

Ref: Selective pressure on SARS-CoV-2 protein coding genes and glycosylation site prediction [Heliyon, 2020]

In all RBD mutations, G431W introduced the highest positive folding energy change at 55.323 kcal/mol,

... -0.616 kcal/mol) induce strongly stabilizing effects on the SARS-Cov-2 RBD (Table1 and Figure 2B ). In all RBD mutations, G431W introduced the highest positive folding energy change at 55.323 kcal/mol, and all mutations in G431 could highly reduce the protein stabilities of RBD and full-length ...

Ref: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity [bioRxiv, 2020-05-23]

In the current study, we predict the affinity of many ACE2 variants for binding to S1 protein using different computational approaches.

... subunit S1. Many missense mutations are reported in various human populations for the ACE2 gene. In the current study, we predict the affinity of many ACE2 variants for binding to S1 protein using different computational approaches. The dissociation process of S1 from some variants of ACE2 is studied in the current ...

Ref: Studying the Effects of ACE2 Mutations on the Stability, Dynamics, and Dissociation Process of SARS-CoV-2 S1/hACE2 Complexes [bioRxiv, 2020]

The detected mutation in the RBD region of one isolate shows stronger binding affinity with human ACE2 than the wild type RBD,

... of RBDs with the ACE2 of different probable natural hosts of corona virus: bat, pangolin and hamster including human. The detected mutation in the RBD region of one isolate shows stronger binding affinity with human ACE2 than the wild type RBD, providing important information regarding its virulence as well as drug targeting. ...

Ref: Sequence analysis of Indian SARS-CoV-2 isolates shows a stronger interaction of mutated receptor binding domain with ACE2 receptor [bioRxiv, 2020-08-28]

H93Y was particularly important,

... domain in SARS-CoV (6, 9) . We observed several mutations within this domain in SARS-CoV-2. H93Y was particularly important, previously being linked in SARS-CoV to the loss of the K ϩ channel and reduced ...

Ref: SARS-CoV-2 and ORF3a: Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis [mSystems, 2020-05-05]

An outlier strain (EPI_ISL_463893) from Bosnia and Herzegovina possessed six aa substitutions.

... reference Wuhan-Hu-1 wherein 84.40% of these strains mutated by only a single amino acid (aa). An outlier strain (EPI_ISL_463893) from Bosnia and Herzegovina possessed six aa substitutions. We also identified 11 residues with high aa mutation frequency, and each contains four types ...

Ref: Comprehensive annotations of the mutational spectra of SARS-CoV-2 spike protein: a fast and accurate pipeline [Transbound. emerg. dis. (Internet), 2020]

Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties.

... whereas the frequency of other sites is continually increasing and now exhibit a worldwide distribution. Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties. We speculate that this improves binding to cellular proteins and hence represents fine-tuning of adaptation ...

Ref: Snapshot of the evolution and mutation patterns of SARS-CoV-2 [bioRxiv, 2020-07-05]

However, our predicted mutations on G431 and S514 have not been seen in the literatures.

... mechanisms of these spatial residues affecting the stabilities of S proteins are similar in SARS-Cov and SARS-Cov-2. However, our predicted mutations on G431 and S514 have not been seen in the literatures. Future experimental investigations should be focused on their topological interaction and biological functions. ...

Ref: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity [bioRxiv, 2020-05-23]

Most of the mutations in F483 of SARS-Cov have not effects on binding affinity and F483R can weaken the interaction.

... can be superimposed to F497 of SARS-Cov-2, F483 shows the different effects on RBD-ACE2 interaction. Most of the mutations in F483 of SARS-Cov have not effects on binding affinity and F483R can weaken the interaction. However, most of mutations in F497 of SARS-Cov-2 can enhance (ΔΔΔG < -0.5 kcal/mol) the ...

Ref: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity [bioRxiv, 2020-05-23]