Comparative analysis of non structural protein 1 of SARS-CoV2 with SARS-CoV1 and MERS-CoV: An i<i>n silico</i>study

Chaudhuri, Ankur

doi:10.1101/2020.06.09.142570

Cited by 8 publications

(9 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…8). Interestingly, however and proximity interactions with POLA1 (which were also detected by AP-MS 6 , and modelled in silico 40 ) were increased. The functional significance (if any) of these and the other gained proximity interactions with the mutant NSP1 remain to be discovered.…”

Section: Host Cell Rna Bindingmentioning

confidence: 75%

A SARS-CoV-2 – host proximity interactome

Samavarchi-Tehrani

Abdouni

Knight

et al. 2020

Preprint

131

View full text Add to dashboard Cite

Viral replication is dependent on interactions between viral polypeptides and host proteins. Identifying virus-host protein interactions can thus uncover unique opportunities for interfering with the virus life cycle via novel drug compounds or drug repurposing. Importantly, many viral-host protein interactions take place at intracellular membranes and poorly soluble organelles, which are difficult to profile using classical biochemical purification approaches. Applying proximity-dependent biotinylation (BioID) with the fast-acting miniTurbo enzyme to 27 SARS-CoV-2 proteins in a lung adenocarcinoma cell line (A549), we detected 7810 proximity interactions (7382 of which are new for SARS-CoV-2) with 2242 host proteins (results available at covid19interactome.org). These results complement and dramatically expand upon recent affinity purification-based studies identifying stable host-virus protein complexes, and offer an unparalleled view of membrane-associated processes critical for viral production. Host cell organellar markers were also subjected to BioID in parallel, allowing us to propose modes of action for several viral proteins in the context of host proteome remodelling. In summary, our dataset identifies numerous high confidence proximity partners for SARS-CoV-2 viral proteins, and describes potential mechanisms for their effects on specific host cell functions.

show abstract

Section: Host Cell Rna Bindingmentioning

confidence: 75%

A SARS-CoV-2 – host proximity interactome

Samavarchi-Tehrani

Abdouni

Knight

et al. 2020

Preprint

131

View full text Add to dashboard Cite

show abstract

“…Nsp1 is the N-terminal product of ORF1ab, cleaved by papain-like proteinase (PLpro) from the polyprotein, promoting host mRNA degradation, blocking translation, and interfering with the innate immune response [ 8 , 9 , 10 , 11 ]. It also binds with ribosomal subunits (40S), inserting its C-terminal region into the entrance position of the channel (ribosomal mRNA), blocking the translation of mRNA [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability

et al. 2021

View full text Add to dashboard Cite

The genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes 16 non-structural (Nsp) and 4 structural proteins. Among the Nsps, Nsp1 inhibits host gene expression and also evades the immune system. This protein has been proposed as a target for vaccine development and also for drug design. Owing to its important role, the current study aimed to identify mutations in Nsp1 and their effect on protein stability and flexibility. This is the first comprehensive study in which 295,000 complete genomes have been screened for mutations after alignment with the Wuhan-Hu-1 reference genome (Accession NC_045512), using the CoVsurver app. The sequences harbored 933 mutations in the entire coding region of Nsp1. The most frequently occurring mutation in the 180-amino-acid Nsp1 protein was R24C (n = 1122), followed by D75E (n = 890), D48G (n = 881), H110Y (n = 860), and D144A (n = 648). Among the 933 non-synonymous mutations, 529 exhibited a destabilizing effect. Similarly, a gain in flexibility was observed in 542 mutations. The majority of the most frequent mutations were detected in the loop regions. These findings imply that Nsp1 mutations might be useful to exploit SARS-CoV-2′s pathogenicity. Genomic sequencing of SARS-CoV-2 on a regular basis will further assist in analyzing variations among the drug targets and to test the diagnostic accuracy. This wide range of mutations and their effect on Nsp1’s stability may have some consequences for the host’s innate immune response to SARS-CoV-2 infection and also for the vaccines’ efficacy. Based on this mutational information, geographically strain-specific drugs, vaccines, and antibody combinations could be a useful strategy against SARS-CoV-2 infection.

show abstract

“…SARS-CoV-2 genome is highly similar with SARS-related coronaviruses 1 derived from Pangolin (Lopes et al 2020) or Bat (Uddin et al 2020;Li et al 2020). A minor dissimilarity might leads to the variation in functionality of SARS-CoV-2 protein with other class of coronaviruses (Chaudhuri 2020). Scientists observing variants in novel coronavirus strains due to mutation, insertion or deletion reported from different geographical regions (Joshi and Paul 2020;Sardar et al 2020;Chang et al 2020).…”

Section: Introductionmentioning

confidence: 99%

A study on non-synonymous mutational patterns in structural proteins of SARS-CoV-2

Das

Roy

2021

Genome

View full text Add to dashboard Cite

SARS-CoV-2 is mutating and creating divergent variants across the world. An in-depth investigation of the amino acid substitutions in the genomic signature of SARS-CoV-2 proteins is highly essential for understanding its host adaptation and infection biology. A total of 9587 SARS-CoV-2 structural protein sequences collected from 49 different countries are used to characterize protein-wise variants, substitution patterns (type and location), and major substitution changes. The majority of the substitutions are distinct, mostly in a particular location, and leads to a change in amino acid's biochemical properties. In terms of mutational changes, Envelope (E) and Membrane (M) proteins are relatively stable than Nucleocapsid (N) and Spike (S) proteins. Several co-occurrence substitutions are observed, particularly in S and N proteins. Substitution specific to active sub-domains reveals that Heptapeptide Repeat, Fusion peptides, Transmembrane in S protein, and N-terminal and C-terminal domains in N protein are remarkably mutated. We also observe a few deleterious mutations in the above domains. The overall study on non-synonymous mutation in structural proteins of SARS-CoV-2 at early in the pandemic indicates a diversity amongst virus sequences.

show abstract

Comparative analysis of non structural protein 1 of SARS-CoV2 with SARS-CoV1 and MERS-CoV: An in silicostudy

Cited by 8 publications

References 49 publications

A SARS-CoV-2 – host proximity interactome

A SARS-CoV-2 – host proximity interactome

Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability

A study on non-synonymous mutational patterns in structural proteins of SARS-CoV-2

Contact Info

Product

Resources

About