Pangolin homology associated with 2019-nCoV

AbstractTo explore potential intermediate host of a novel coronavirus is vital to rapidly control continuous COVID-19 spread. We found genomic and evolutionary evidences of the occurrence of 2019-nCoV-like coronavirus (named as Pangolin-CoV) from dead Malayan Pangolins. Pangolin-CoV is 91.02% and 90.55% identical at the whole genome level to 2019-nCoV and BatCoV RaTG13, respectively. Pangolin-CoV is the lowest common ancestor of 2019-nCoV and RaTG13. The S1 protein of Pangolin-CoV is much more closely related to 2019-nCoV than RaTG13. Five key amino-acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and 2019-nCoV but four amino-acid mutations occur in RaTG13. It indicates Pangolin-CoV has similar pathogenic potential to 2019-nCoV, and would be helpful to trace the origin and probable intermediate host of 2019-nCoV.

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On the Identification of Clinically Relevant Bacterial Amino Acid Changes at the Whole Genome Level Using Auto-PSS-Genome

Interdisciplinary Sciences Computational Life Sciences ◽

10.1007/s12539-021-00439-2 ◽

2021 ◽

Author(s):

Hugo López-Fernández ◽

Cristina P. Vieira ◽

Pedro Ferreira ◽

Paula Gouveia ◽

Florentino Fdez-Riverola ◽

...

Keyword(s):

Amino Acid ◽

Whole Genome ◽

Genome Level

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Genetic Variation and Evolution of the 2019 Novel Coronavirus

Public Health Genomics ◽

10.1159/000513530 ◽

2021 ◽

pp. 1-13

Author(s):

Salvatore Dimonte ◽

Muhammed Babakir-Mina ◽

Taib Hama-Soor ◽

Salar Ali

Keyword(s):

Amino Acid ◽

Receptor Binding ◽

Rapid Evolution ◽

Single Amino Acid ◽

Angiotensin Converting Enzyme 2 ◽

New Type ◽

Amino Acid Mutations ◽

Host Infection ◽

Human Coronaviruses ◽

Novel Coronavirus

Introduction: SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. Methods: This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. Results: The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. Discussion/Conclusion: Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

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Geographical Distribution of Amino Acid Mutations in Human SARS-CoV-2 Orf1ab Poly-Proteins Compared to the Equivalent Reference Proteins from China

10.26434/chemrxiv.12951617.v1 ◽

2020 ◽

Author(s):

Kunchur Guruprasad

Keyword(s):

Amino Acid ◽

North America ◽

South America ◽

Protein Sequences ◽

Sequence Length ◽

Amino Acid Residues ◽

Deletion Mutations ◽

Leader Protein ◽

Amino Acid Mutations ◽

Geographical Locations

Mutations in orf1ab poly-protein sequences from human SARS-CoV-2 isolates representing six geographical locations were identified by comparing with the equivalent reference sequences from the Wuhan-Hu-1, China isolate, epicentre of the current COVID-19 pandemic disease. The orf1ab poly-proteins of sequence length 7096 amino acid residues representing 10,929 genomes from six geographical locations comprised a total of 27,895 mutations that corresponded to 2,095 distinct mutation sites. The percentage of mutations was significantly high for RdRp (33.47%), nsp2 (20.04%), helicase (15.95%) and nsp3 (12.61%) proteins, compared to rest of the proteins which ranged between (0.14%) for nsp10 to (2.79%) for nsp6 proteins. A total of 2715 mutations were observed for the unique mutation sites identified for each of the six geographical locations. The distribution of the mutations was; Africa (87), Asia (605), Europe (134), North America (1677), Oceania (200) and South America (12). The RdRp protein contained significantly high mutation percentage (>31%) that varied among the different geographical locations. The nsp2 proteins from Asia, North America, Oceania and South America, the nsp3 proteins from Africa and Europe and the helicase proteins from North America showed high mutation percentage next to the RdRp proteins. The P4715L mutation in RdRp, T265I in nsp2 and L3606F in nsp6 were observed in all the geographical locations with the RdRp P4715L mutation being predominant among the orf1ab poly-proteins. In another dataset comprising 158 genomes in which the orf1ab poly-proteins comprised sequences of variable length between 7084-7095 amino acid residues, 88 additional distinct mutations were observed for the six geographical locations that included deletion mutations. The proteins containing deletion mutations were; leader protein, nsp2, nsp3, nsp4, nsp6, RdRp, 3’ -to-5’ exonuclease and endoRNAse. In this work, all the mutations observed in 11,087 orf1ab poly-proteins of human SARS CoV-2 comprising between 7084-7096 amino acid residues with reference to the human SARS-CoV-2 orf1ab poly-protein sequences from Wuhan-Hu-1, China and representing the six geographical locations; Africa, Asia, Europe, North America, Oceania and South America are presented.

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Whole-genome Sequencing of SARS-CoV-2: Using Phylogeny and Structural Modeling to Contextualize Local Viral Evolution

Military Medicine ◽

10.1093/milmed/usab031 ◽

2021 ◽

Author(s):

Ashley E Nazario-Toole ◽

Hui Xia ◽

Thomas F Gibbons

Keyword(s):

Amino Acid ◽

Phylogenetic Trees ◽

Sequence Data ◽

Viral Evolution ◽

Vaccine Design ◽

Whole Genome ◽

Structural Protein ◽

Protein Amino Acid ◽

Clinical Specimens ◽

Amino Acid Mutations

ABSTRACT Introduction The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global pandemic resulting in over 1 million deaths worldwide. In the Department of Defense (DoD), over 129,000 personnel (civilians, dependents, and active duty) have been infected with the virus to date. Rapid estimations of transmission and mutational patterns of virus outbreaks can be accomplished using whole-genome viral sequencing. Deriving interpretable and actionable results from pathogen sequence data is accomplished by the construction of phylogenetic trees (from local and global virus sequences) and by the creation of protein maps, to visualize and predict the effects of structural protein amino acid mutations. Materials and Methods We developed a sequencing and bioinformatics workflow for molecular epidemiological SARS-CoV-2 surveillance using excess clinical specimens collected under an institutional review board exempt protocol at Joint Base San Antonio, Lackland AFB. This workflow includes viral RNA isolation, viral load quantification, tiling-based next-generation sequencing, sequencing and bioinformatics analysis, and data visualization via phylogenetic trees and protein mapping. Results Sequencing of 37 clinical specimens collected at JBSA/Lackland revealed that by June 2020, SAR-CoV-2 strains carrying the 614G mutation were the predominant cause of local coronavirus disease 2019 infections. We identified 109 nucleotide changes in the coding region of the SARS-CoV-2 genome (which lead to 63 unique, non-synonymous amino acid mutations), one mutation in the 5ʹ-untranslated region (UTR), and two mutations in the 3ʹUTR. Furthermore, we identified and mapped six additional spike protein amino acid changes—information which could potentially aid vaccine design. Conclusion The workflow presented here is designed to enable DoD public health officials to track viral evolution and conduct near real-time evaluation of future outbreaks. The generation of molecular epidemiological sequence data is critical for the development of disease intervention strategies—most notably, vaccine design. Overall, we present a streamlined sequencing and bioinformatics methodology aimed at improving long-term readiness efforts in the DoD.

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Structural Insights Into the Design of Peptide-based Drug or Diagnostic Reagent Antagonizing SARS-COV-2

10.21203/rs.3.rs-45305/v1 ◽

2020 ◽

Author(s):

junhao jiang ◽

Ping Deng

Keyword(s):

Amino Acid ◽

Binding Affinity ◽

Great Promise ◽

Amino Acid Residues ◽

Important Amino Acid ◽

Amino Acid Mutations ◽

Α Helix ◽

New Interactions ◽

Structural Insights ◽

Blocking Capacity

Abstract Background Very limited drug and diagnostic reagents are currently available to tackle the emergence of SARS-CoV-2. However, recent findings about the structure of the complex about PD of ACE2 and RBD of SARS-CoV-2 spike protein hold great promise for the design of novel vaccines and peptides. To provide some suggestions for the design of peptide-based drug or diagnostic reagents antagonizing SARS-CoV-2, and describe the interactions between the receptor-binding domain of SARS-CoV-2 and PD domain of its receptor, ACE2. Methods Based on the PD-RBD crystal structure, the molecular interaction details of PD-RBD was contrasted. Results Amino acid mutations located in RBM of SARS-CoV result in the formation of new interactions between SARS-CoV-2 and α-helix 1, which can increase the binding affinity of SARS-CoV-2 to ACE2. It is confirmed that the α-helix 1 on ACE2 is the most important domain for binding spike glycoprotein of SARS-CoV-2, which can be used as a leading peptide for drug and diagnostic reagents development. Conclusion Based on the molecular-level characterization analysis between the PD and RBD, severe important amino acid residues (Q24, T27, K31, and H34) on α-helix 1 are proposed to mutate into increasing the binding affinity. Although the information provided in this study is predictive and based on no experimental evidence, it may provide useful suggestions for the experimental scientists to synthesize the proposed peptide and test their binding affinity and blocking capacity, and may be helpful for the understanding of SARS-CoV-2 entry.

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Evolutionary Process of Amino Acid Biosynthesis in Corynebacterium at the Whole Genome Level

Molecular Biology and Evolution ◽

10.1093/molbev/msh175 ◽

2004 ◽

Vol 21 (9) ◽

pp. 1683-1691 ◽

Cited By ~ 21

Author(s):

Yousuke Nishio ◽

Yoji Nakamura ◽

Yoshihiro Usuda ◽

Shinichi Sugimoto ◽

Kazuhiko Matsui ◽

...

Keyword(s):

Amino Acid ◽

Evolutionary Process ◽

Amino Acid Biosynthesis ◽

Whole Genome ◽

Acid Biosynthesis ◽

Genome Level

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Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

10.1101/2020.03.16.993816 ◽

2020 ◽

Cited By ~ 7

Author(s):

Jiao-Mei Huang ◽

Syed Sajid Jan ◽

Xiaobin Wei ◽

Yi Wan ◽

Songying Ouyang

Keyword(s):

Public Health ◽

Amino Acid ◽

Recombinant Virus ◽

Spike Protein ◽

Whole Genome ◽

Amino Acid Residues ◽

Global Public Health ◽

Whole Genome Analysis ◽

Coding Regions ◽

Genomic Similarity

SUMMARYThe recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability.

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Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

10.20944/preprints202003.0395.v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Kunal Dutta ◽

Sergey Shityakov ◽

Olga Morozova ◽

Ibrahim Khalifa ◽

Jin Zhang ◽

...

Keyword(s):

Amino Acid ◽

Rna Polymerase ◽

Rna Synthesis ◽

Binding Free Energy ◽

Polymerase Activity ◽

Amino Acid Residues ◽

Rna Dependent Rna Polymerase ◽

Recent Emergence ◽

Novel Coronavirus ◽

Major Amino Acid

Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25o C beclabuvir, a non-nucleoside inhibitor of the RdRpHCV can efficiently bind to RdRp SARS-CoV-2 (ΔGAutoDock = -9.95 kcal mol-1) with an inhibition constant of 51.03 nM. Both the ΔGLondon and ΔGGBVI / WSA values were - 9.06 and - 6.67 kcal mol-1, respectively for binding of beclabuvir to RdRpSARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRpSARS-CoV-2 (ΔGvina = -8.0 kcal mol-1) than that observed with the Thumb 1 domain of RdRpHCV (ΔGvina = -7.1 kcal mol-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549th to 776th amino acid residues of RdRpSARS-CoV, where the major amino acid residues interacting being I591, Y621, C624, D625, A690, N693, L760, D762, D763, and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRpSARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.

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Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

10.20944/preprints202003.0395.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Kunal Dutta ◽

Sergey Shityakov ◽

Olga Morozova ◽

Ibrahim Khalifa ◽

Jin Zhang ◽

...

Keyword(s):

Amino Acid ◽

Rna Polymerase ◽

Rna Synthesis ◽

Therapeutic Potential ◽

Binding Free Energy ◽

Polymerase Activity ◽

Amino Acid Residues ◽

Rna Dependent Rna Polymerase ◽

Recent Emergence ◽

Novel Coronavirus

Recent emergence of novel coronavirus (SARS-CoV-2) in Wuhan, China has resulted more than 14,510 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between well-known antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25o C beclabuvir, a non-nucleoside inhibitor of the RdRp of the HCV can efficiently bind to RdRp of the SARS-CoV-2 (ΔGAutoDock = -9.95 kcal mol-1) with an inhibition constant of only 51.03 nM. Both the ΔGLondon and ΔGGBVI / WSA values were - 9.06 and - 6.67 kcal mol-1, respectively for SARS-CoV-2. In addition, beclabuvir also shows better binding free energy (ΔGvina = 9.7 kcal mol-1) than that of the Thumb 1 domain of RdRp of HCV (ΔGvina = 7.7 kcal mol-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity existed within 549 to 776 amino acid residues of RdRp. Moreover, major interacting amino acid residues were I591, Y621, C624, D625, A690, N693, L760, D762, D763 and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRp which is essential for viral RNA synthesis. In conclusion, results suggest beclabuvir has high therapeutic potential as an anti-SARS-CoV-2 drug.

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Evolutionary dynamics of bovine coronaviruses: natural selection pattern of the spike gene implies adaptive evolution of the strains

Journal of General Virology ◽

10.1099/vir.0.054940-0 ◽

2013 ◽

Vol 94 (9) ◽

pp. 2036-2049 ◽

Cited By ~ 25

Author(s):

Mehdi R. M. Bidokhti ◽

Madeleine Tråvén ◽

Neel K. Krishna ◽

Muhammad Munir ◽

Sándor Belák ◽

...

Keyword(s):

Amino Acid ◽

Adaptive Evolution ◽

Evolutionary Dynamics ◽

Common Ancestor ◽

Protein Gene ◽

Interspecies Transmission ◽

Amino Acid Residues ◽

S Protein ◽

Spike Gene ◽

Selection Pattern

Coronaviruses demonstrate great potential for interspecies transmission, including zoonotic outbreaks. Although bovine coronavirus (BCoV) strains are frequently circulating in cattle farms worldwide, causing both enteric and respiratory disease, little is known about their genomic evolution. We sequenced and analysed the full-length spike (S) protein gene of 33 BCoV strains from dairy and feedlot farms collected during outbreaks that occurred from 2002 to 2010 in Sweden and Denmark. Amino acid identities were >97 % for the BCoV strains analysed in this work. These strains formed a clade together with Italian BCoV strains and were highly similar to human enteric coronavirus HECV-4408/US/94. A high similarity was observed between BCoV, canine respiratory coronavirus (CRCoV) and human coronavirus OC43 (HCoV-OC43). Molecular clock analysis of the S gene sequences estimated BCoV and CRCoV diverged from a common ancestor in 1951, while the time of divergence from a common ancestor of BCoV and HCoV-OC43 was estimated to be 1899. BCoV strains showed the lowest similarity to equine coronavirus, placing the date of divergence at the end of the eighteenth century. Two strongly positive selection sites were detected along the receptor-binding subunit of the S protein gene: spanning amino acid residues 109–131 and 495–527. By contrast, the fusion subunit was observed to be under negative selection. The selection pattern along the S glycoprotein implies adaptive evolution of BCoVs, suggesting a successful mechanism for BCoV to continuously circulate among cattle and other ruminants without disappearance.

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