Molecular Evolutionary Characteristics of the 2019 Novel Coronavirus (SARS-CoV-2) Contracted by Tunisian Citizens: Comparison and Relationship to Other Human and Animal Coronaviruses Based on Spike Glycoprotein-Coding Gene Sequences Analysis

In contributing to the initiative to address the COVID-19 pandemic and in order to enhance the knowledge on driving forces shaping the evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (isolated from Tunisian patients), a comparison in relation to other coronaviruses infecting humans (SARS-CoV-1, MERS-CoV, HCoV/229E, HCoV/NL63, HCoV/OC43, and HCoV/HKU1) as well as animals (SARS-CoVs in tiger, bats, civet, pangolin, bovine, and MERS-CoV in dromedary/camel), was conducted. In-depth analysis was carried out involving 115 sequences of spike glycoprotein-coding gene extracted from the international databases. Phylogeny inference allowed the reconstruction of a bifurcating tree where four distinct groups were delineated and at the same time, three animal accessions (SARS-CoV-2/tiger, MERS-CoV/camel, and SARS-CoV/bovine) shifted from the animal group and integrated the human coronaviruses clades. Nonetheless, in the presence of reticulate events such as recombination, networks described better the phylogenetic relationships rather than the classic dendrogram. Thus, networks were produced and identified four clusters containing sharply demarcated subgroups (eight subdivisions). Except networked phylogenies of SARS-CoV-1, SARS-CoV-2, and HCoV/HKU1, all the others showed edges and boxes illustrating the occurrence of incompatibilities related to the sequences of spike glycoprotein-coding gene. Thereby and consolidating this result, three methods (RDP package, GARD, and RECCO) were used to detect breakpoints in aligned sequences. Except the clades SARS-CoV-1 and SARS-CoV-2, all the remaining phylogenetic subdivisions were subject to recombination. Furthermore, the screening of selection pressure in all studied sequences by various statistics-based models of the HyPhy package, showed that, similarly, the lineages belonging to the clades SARS-CoV-1 and SARS-CoV-2 were not under selection. In contrast, all members of the remaining clades underwent, to different extents, adaptive selection as well as purifying selection.

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Emergence of SARS-CoV-2 through recombination and strong purifying selection

Science Advances ◽

10.1126/sciadv.abb9153 ◽

2020 ◽

Vol 6 (27) ◽

pp. eabb9153 ◽

Cited By ~ 49

Author(s):

Xiaojun Li ◽

Elena E. Giorgi ◽

Manukumar Honnayakanahalli Marichannegowda ◽

Brian Foley ◽

Chuan Xiao ◽

...

Keyword(s):

Host Species ◽

Purifying Selection ◽

New Drugs ◽

Evolutionary Constraints ◽

Binding Motif ◽

The Novel ◽

Global Pandemic ◽

Show Evidence ◽

Human Coronaviruses ◽

Novel Coronavirus

COVID-19 has become a global pandemic caused by the novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis, discovering new drugs, and developing a vaccine. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike and other genes among bat, pangolin, and human coronaviruses, suggesting similar evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. Similar purifying selection in different host species, together with frequent recombination among coronaviruses, suggests a common evolutionary mechanism that could lead to new emerging human coronaviruses.

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Emergence of SARS-CoV-2 through Recombination and Strong Purifying Selection

10.1101/2020.03.20.000885 ◽

2020 ◽

Cited By ~ 34

Author(s):

Xiaojun Li ◽

Elena E. Giorgi ◽

Manukumar Honnayakanahalli Marichann ◽

Brian Foley ◽

Chuan Xiao ◽

...

Keyword(s):

Host Species ◽

Vaccine Development ◽

Purifying Selection ◽

Evolutionary Constraints ◽

Binding Motif ◽

Spike Gene ◽

Global Pandemic ◽

Show Evidence ◽

Human Coronaviruses ◽

Novel Coronavirus

AbstractCOVID-19 has become a global pandemic caused by a novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis and for drug discovery and vaccine development. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike gene and in other genes among bat, pangolin and human coronaviruses, indicating similar strong evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. Similar purifying selection in different host species and frequent recombination among coronaviruses suggest a common evolutionary mechanism that could lead to new emerging human coronaviruses.One Sentence SummaryExtensive Recombination and Strong Purifying Selection among coronaviruses from different hosts facilitate the emergence of SARS-CoV-2

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Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

Infectious Disorders - Drug Targets ◽

10.2174/1871526520666200804161650 ◽

2020 ◽

Vol 20 ◽

Author(s):

Bipin Singh

Keyword(s):

Receptor Binding ◽

Point Mutations ◽

Binding Domain ◽

Receptor Binding Domain ◽

Spike Glycoprotein ◽

Angiotensin Converting Enzyme 2 ◽

Recent Outbreak ◽

Novel Coronavirus ◽

Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

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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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Bioactive Terpenes and Their Derivatives as Potential SARS-CoV-2 Proteases Inhibitors from Molecular Modeling Studies

Biomolecules ◽

10.3390/biom11010074 ◽

2021 ◽

Vol 11 (1) ◽

pp. 74

Author(s):

Lúcio Ricardo Leite Diniz ◽

Yunierkis Perez-Castillo ◽

Hatem A. Elshabrawy ◽

Carlos da Silva Maia Bezerra Filho ◽

Damião Pergentino de Sousa

Keyword(s):

Natural Products ◽

Healthcare Systems ◽

New Drugs ◽

Therapeutic Approaches ◽

Elderly Individuals ◽

Global Challenge ◽

Molecular Modeling Studies ◽

Human Coronaviruses ◽

Novel Coronavirus ◽

Chronic Comorbidities

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus; the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Millions of cases and deaths to date have resulted in a global challenge for healthcare systems. COVID-19 has a high mortality rate, especially in elderly individuals with pre-existing chronic comorbidities. There are currently no effective therapeutic approaches for the prevention and treatment of COVID-19. Therefore, the identification of effective therapeutics is a necessity. Terpenes are the largest class of natural products that could serve as a source of new drugs or as prototypes for the development of effective pharmacotherapeutic agents. In the present study, we discuss the antiviral activity of these natural products and we perform simulations against the Mpro and PLpro enzymes of SARS-CoV-2. Our results strongly suggest the potential of these compounds against human coronaviruses, including SARS-CoV-2.

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SARS-CoV-2 and human milk: what is the evidence?

10.1101/2020.04.07.20056812 ◽

2020 ◽

Cited By ~ 7

Author(s):

Kimberly A. Lackey ◽

Ryan M. Pace ◽

Janet E. Williams ◽

Lars Bode ◽

Sharon M. Donovan ◽

...

Keyword(s):

Public Health ◽

Human Milk ◽

Vertical Transmission ◽

Published Data ◽

Single Study ◽

Public Health Challenges ◽

Specific Igg ◽

Health Communities ◽

Human Coronaviruses ◽

Novel Coronavirus

ABSTRACTThe novel coronavirus SARS-CoV-2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical, and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. While respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS-CoV-2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on April 17, 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS-CoV in human milk (it was negative); and no published data on MERS-CoV and human milk. We identified 12 studies reporting human milk tested for SARS-CoV-2; one study detected the virus in one milk sample, and another study detected SARS-CoV-2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.

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Human coronaviruses: ophthalmic manifestations

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2020-000630 ◽

2020 ◽

Vol 5 (1) ◽

pp. e000630

Author(s):

Mohd-Asyraaf Abdul-Kadir ◽

Lik Thai Lim

Keyword(s):

Viral Entry ◽

Ocular Surface ◽

Animal Studies ◽

Preliminary Finding ◽

Ocular Manifestations ◽

Ophthalmic Manifestations ◽

Global Pandemic ◽

Conflicting Evidence ◽

Human Coronaviruses ◽

Novel Coronavirus

The 2019 novel coronavirus which causes severe acute respiratory syndrome (SARS) known as SARS-CoV-2 still remains as a global pandemic since its discovery and continues to spread across the world, given how highly contagious the virus is. We reviewed various articles that explore eye involvement in COVID-19 and other human coronaviruses, its human manifestations in comparison to animal studies and potential mechanism of viral entry into the eye surface. Evidence of animal studies depicted various complications of coronaviruses infection into the eyes, in both anterior and posterior segments of the eye. Conjunctival inflammation remains uncommon in association with COVID-19, with other ophthalmic findings. The risk of transmission via the ocular surface remains likely low, though it is inarguably present based on preliminary finding of viral load in ocular samples and expression of ACE2 on the ocular surface. Testing the tears sample for diagnosing SARS-CoV-2 was unreliable due to limitations of the testing kits and conflicting evidence of the viral titre in the ocular samples. Further larger, more precise and specific studies are required to allow us to better understand the pattern of virulence underlying the associations of SARS-CoV-2 in the eye despite its rare occurrence. This review article aims to enhance better awareness among clinicians regarding ocular manifestations associated with COVID-19 and necessary precautions should be implemented to minimise the risk of person-to-person especially in the nosocomial setting.

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Nanobiosensors for the Detection of Novel Coronavirus 2019-nCoV and Other Pandemic/Epidemic Respiratory Viruses: A Review

Sensors ◽

10.3390/s20226591 ◽

2020 ◽

Vol 20 (22) ◽

pp. 6591

Author(s):

Badriyah Alhalaili ◽

Ileana Nicoleta Popescu ◽

Olfa Kamoun ◽

Feras Alzubi ◽

Sami Alawadhia ◽

...

Keyword(s):

Public Health ◽

Vaccine Development ◽

Respiratory Viruses ◽

Public Health Emergency ◽

Detection Methods ◽

Origin And Evolution ◽

The World ◽

Human Coronaviruses ◽

Novel Coronavirus ◽

Made In

The coronavirus disease 2019 (COVID-19) pandemic is considered a public health emergency of international concern. The 2019 novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused this pandemic has spread rapidly to over 200 countries, and has drastically affected public health and the economies of states at unprecedented levels. In this context, efforts around the world are focusing on solving this problem in several directions of research, by: (i) exploring the origin and evolution of the phylogeny of the SARS-CoV-2 viral genome; (ii) developing nanobiosensors that could be highly effective in detecting the new coronavirus; (iii) finding effective treatments for COVID-19; and (iv) working on vaccine development. In this paper, an overview of the progress made in the development of nanobiosensors for the detection of human coronaviruses (SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV) is presented, along with specific techniques for modifying the surface of nanobiosensors. The newest detection methods of the influenza virus responsible for acute respiratory syndrome were compared with conventional methods, highlighting the newest trends in diagnostics, applications, and challenges of SARS-CoV-2 (COVID-19 causative virus) nanobiosensors.

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Computational Inference of Selection Underlying the Evolution of the Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2

Journal of Virology ◽

10.1128/jvi.00411-20 ◽

2020 ◽

Vol 94 (12) ◽

Cited By ~ 45

Author(s):

Rachele Cagliani ◽

Diego Forni ◽

Mario Clerici ◽

Manuela Sironi

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Positive Selection ◽

Common Ancestor ◽

Purifying Selection ◽

Population Variation ◽

Binding Motif ◽

The Novel ◽

Species Barrier ◽

The Common ◽

Novel Coronavirus

ABSTRACT The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that recently emerged in China is thought to have a bat origin, as its closest known relative (BatCoV RaTG13) was described previously in horseshoe bats. We analyzed the selective events that accompanied the divergence of SARS-CoV-2 from BatCoV RaTG13. To this end, we applied a population genetics-phylogenetics approach, which leverages within-population variation and divergence from an outgroup. Results indicated that most sites in the viral open reading frames (ORFs) evolved under conditions of strong to moderate purifying selection. The most highly constrained sequences corresponded to some nonstructural proteins (nsps) and to the M protein. Conversely, nsp1 and accessory ORFs, particularly ORF8, had a nonnegligible proportion of codons evolving under conditions of very weak purifying selection or close to selective neutrality. Overall, limited evidence of positive selection was detected. The 6 bona fide positively selected sites were located in the N protein, in ORF8, and in nsp1. A signal of positive selection was also detected in the receptor-binding motif (RBM) of the spike protein but most likely resulted from a recombination event that involved the BatCoV RaTG13 sequence. In line with previous data, we suggest that the common ancestor of SARS-CoV-2 and BatCoV RaTG13 encoded/encodes an RBM similar to that observed in SARS-CoV-2 itself and in some pangolin viruses. It is presently unknown whether the common ancestor still exists and, if so, which animals it infects. Our data, however, indicate that divergence of SARS-CoV-2 from BatCoV RaTG13 was accompanied by limited episodes of positive selection, suggesting that the common ancestor of the two viruses was poised for human infection. IMPORTANCE Coronaviruses are dangerous zoonotic pathogens; in the last 2 decades, three coronaviruses have crossed the species barrier and caused human epidemics. One of these is the recently emerged SARS-CoV-2. We investigated how, since its divergence from a closely related bat virus, natural selection shaped the genome of SARS-CoV-2. We found that distinct coding regions in the SARS-CoV-2 genome evolved under conditions of different degrees of constraint and are consequently more or less prone to tolerate amino acid substitutions. In practical terms, the level of constraint provides indications about which proteins/protein regions are better suited as possible targets for the development of antivirals or vaccines. We also detected limited signals of positive selection in three viral ORFs. However, we warn that, in the absence of knowledge about the chain of events that determined the human spillover, these signals should not be necessarily interpreted as evidence of an adaptation to our species.

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COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein

Biology Direct ◽

10.1186/s13062-020-00275-2 ◽

2020 ◽

Vol 15 (1) ◽

Cited By ~ 4

Author(s):

Sepehr Ehsani

Keyword(s):

Respiratory Infections ◽

Binding Capacity ◽

Sequence Similarity ◽

Cytoplasmic Tail ◽

Research Field ◽

Spike Protein ◽

Spike Glycoprotein ◽

Surface Receptors ◽

Evolutionary Connection ◽

Novel Coronavirus

Abstract The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed.

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