scholarly journals Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes

2020 ◽  
Author(s):  
Hua Guo ◽  
Bing-Jie Hu ◽  
Xing-Lou Yang ◽  
Lei-Ping Zeng ◽  
Bei Li ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Positive Selection ◽  
Binding Affinity ◽  
Arms Race ◽  
Spike Protein ◽  
Interspecies Transmission ◽  
Evolutionary Arms Race ◽  
Horseshoe Bat ◽  
Key Residues ◽  
Spike Proteins

AbstractThe Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. It is speculated that the interaction between bat ACE2 and SARSr-CoV spike proteins drives diversity. Here, we have identified a series of R. sinicus ACE2 variants with some polymorphic sites involved in the interaction with the SARS-CoV spike protein. Pseudoviruses or SARSr-CoVs carrying different spike proteins showed different infection efficiency in cells transiently expressing bat ACE2 variants. Consistent results were observed by binding affinity assays between SARS- and SARSr-CoV spike proteins and receptor molecules from bats and humans. All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with their SARS-CoV counterpart. Structure modeling revealed that the difference in binding affinity between spike and ACE2 might be caused by the alteration of some key residues in the interface of these two molecules. Molecular evolution analysis indicates that these residues were under strong positive selection. These results suggest that the SARSr-CoV spike protein and R. sinicus ACE2 may have coevolved over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics. It further proves that R. sinicus is the natural host of SARSr-CoVs.ImportanceEvolutionary arms race dynamics shape the diversity of viruses and their receptors. Identification of key residues which are involved in interspecies transmission is important to predict potential pathogen spillover from wildlife to humans. Previously, we have identified genetically diverse SARSr-CoV in Chinese horseshoe bats. Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. These ACE2 variants support SARS- and SARSr-CoV infection but with different binding affinity to different spike proteins. The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity of spillover to humans. The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests a long-term and ongoing coevolutionary dynamics between them. Continued surveillance of this group of viruses in bats is necessary for the prevention of the next SARS-like disease.

scholarly journals Evolutionary Arms Race between Virus and Host Drives Genetic Diversity in Bat Severe Acute Respiratory Syndrome-Related Coronavirus Spike Genes

2020 ◽  
Vol 94 (20) ◽  
Author(s):  
Hua Guo ◽  
Bing-Jie Hu ◽  
Xing-Lou Yang ◽  
Lei-Ping Zeng ◽  
Bei Li ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Severe Acute Respiratory Syndrome ◽  
Binding Affinity ◽  
Arms Race ◽  
Spike Protein ◽  
Content Type ◽  
Evolutionary Arms Race ◽  
Horseshoe Bat ◽  
Key Residues ◽  
Spike Proteins

ABSTRACT The Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. It is speculated that the interaction between bat ACE2 and SARSr-CoV spike proteins drives diversity. Here, we identified a series of R. sinicus ACE2 variants with some polymorphic sites involved in the interaction with the SARS-CoV spike protein. Pseudoviruses or SARSr-CoVs carrying different spike proteins showed different infection efficiencies in cells transiently expressing bat ACE2 variants. Consistent results were observed by binding affinity assays between SARS-CoV and SARSr-CoV spike proteins and receptor molecules from bats and humans. All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with that of their SARS-CoV counterpart. Structure modeling revealed that the difference in binding affinity between spike and ACE2 might be caused by the alteration of some key residues in the interface of these two molecules. Molecular evolution analysis indicates that some key residues were under positive selection. These results suggest that the SARSr-CoV spike protein and R. sinicus ACE2 may have coevolved over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics. IMPORTANCE Evolutionary arms race dynamics shape the diversity of viruses and their receptors. Identification of key residues which are involved in interspecies transmission is important to predict potential pathogen spillover from wildlife to humans. Previously, we have identified genetically diverse SARSr-CoVs in Chinese horseshoe bats. Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. These ACE2 variants support SARS-CoV and SARSr-CoV infection but with different binding affinities to different spike proteins. The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity for spillover to humans. The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests long-term and ongoing coevolutionary dynamics between them. Continued surveillance of this group of viruses in bats is necessary for the prevention of the next SARS-like disease.

scholarly journals Harnessing the Sars-cov-2 Spike Protein Binding Affinity to Ace2 Receptor Through Narcotinic Compounds Combined With Adjuvants: an in Silico Insight

2021 ◽  
Author(s):  
Saeedeh Mohammadi ◽  
Esmail Doustkhah ◽  
Nader Sakhaee ◽  
Ayoub Esmailpour ◽  
Mohammad Esmailpour
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Muramyl Dipeptide ◽  
Docking Studies ◽  
Spike Protein ◽  
Binding Affinities ◽  
Narcotic Analgesics ◽  
S Protein ◽  
Suitable Combination ◽  
Spike Proteins

Abstract Protein products of SARS-CoV-2 spike (S) coding gene sequence, were all analyzed and compared to other SARS-CoV S proteins to elucidate structural similarities of spike proteins. A homology modeling of SARS-CoV-2 S protein was obtained and used in molecular docking studies to find binding affinities of spike protein for angiotensin-converting enzyme 2 (ACE2). The two most important binding sites of S protein, namely, RBD and CTD, critically responsible for binding interactions, were identified. Finally, binding affinity of RBD and CTD domains of S protein with narcotic analgesics are studied. Moreover, interactions of ACE2 receptor- S protein with narcotic compounds when mixed with small molecule adjuvants to improve the immune response and increase the efficacy of potential vaccines, were taken into consideration. In-silico results suggest that the combination of narcotine hemiacetal with mannide monooleate shows a stronger binding affinity with CTD, while carprofen-muramyl dipeptide and squalene have stronger binding affinities for the RBD portion of S protein. Thus, a suitable combination of these narcotic is proposed to yield potent site-blocking efficacy for ACE2 receptor against SARS-CoV-2 spike proteins.

scholarly journals The Red Queen’s Crown: an evolutionary arms race between coronaviruses and mammalian species reflected in positive selection of the ACE2 receptor among many species

2020 ◽  
Author(s):  
Mehrdad Hajibabaei ◽  
Gregory A. C. Singer
Keyword(s):  
Positive Selection ◽  
Mammalian Species ◽  
Critical Role ◽  
Arms Race ◽  
Host Cells ◽  
Tasmanian Devil ◽  
Diverse Range ◽  
Evolutionary Response ◽  
Evolutionary Arms Race ◽  
Selection Of

AbstractThe world is going through a global viral pandemic with devastating effects on human life and socioeconomic activities. This pandemic is the result of a zoonotic coronavirus, Severe Acute Respirsatory Syndrom Coronavirus 2 (SARS-CoV-2) which is believed to have originated in bats and transferred to humans possibly through an intermediate host species (Zhou et al. 2020; Coronaviridae Study Group of the International Committee on Taxonomy of Viruses 2020). The virus attacks host cells by attaching to a cell membrane surface protein receptor called ACE2 (Ge et al. 2013; Zhou et al. 2020). Given the critical role of ACE2 as a binding receptor for a number of coronaviruses, we studied the molecular evolution of ACE2 in a diverse range of mammalian species. Using ACE2 as the target protein, we wanted to specifically test the Red Queen hypothesis (Dawkins and Krebs 1979) where the parasite and host engage in an evolutionary arms race which can result in positive selection of their traits associated to their fitness and survival. Our results clearly show a phylogenetically broad evolutionary response, in the form of positive selection detected at the codon-level in ACE2. We see positive selection occurring at deep branches as well as 13 incidents at the species level. We found the strongest level of positive selection in Tasmanian devil (Sarcophilus harrisii), donkey (Equus asinus), large flying fox (Pteropus vampyrus), Weddell seal (Leptonychotes weddellii), and dog (Canis lupus familiaris). At the codon-level, we found up to 10% of ACE2 codons are impacted by positive selection in the mammalian lineages studied. This phylogenetically broad evolutionary arms race can contribute to the emergence of new strains of coronaviruses in different mammalian lineages with a potential to transfer between species given the common binding receptor ACE2. Our study provides a molecular evolutionary perspective to the current pandemic and sheds light on its evolutionary mechanisms.“Nothing in biology makes sense except in the light of evolution” (Theodosius Dobzhansky)

scholarly journals Cryo-electron Microscopy Structure of the Swine Acute Diarrhea Syndrome Coronavirus Spike Glycoprotein Provides Insights into Evolution of Unique Coronavirus Spike Proteins

2020 ◽  
Vol 94 (22) ◽  
Author(s):  
Hongxin Guan ◽  
Youwang Wang ◽  
Vanja Perčulija ◽  
Abdullah F. U. H. Saeed ◽  
Yichang Liu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Immune Evasion ◽  
Acute Diarrhea ◽  
Structural Features ◽  
The Other ◽  
Spike Protein ◽  
Interspecies Transmission ◽  
Cryo Electron Microscopy ◽  
Diarrhea Syndrome ◽  
Spike Proteins

ABSTRACT Coronaviruses (CoV) have caused a number of major epidemics in humans and animals, including the current pandemic of coronavirus disease 2019 (COVID-19), which has brought a renewed focus on the evolution and interspecies transmission of coronaviruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), which was recently identified in piglets in southern China, is an alphacoronavirus that originates from the same genus of horseshoe bats as severe acute respiratory syndrome CoV (SARS-CoV) and that was reported to be capable of infecting cells from a broad range of species, suggesting a considerable potential for interspecies transmission. Given the importance of the coronavirus spike (S) glycoprotein in host range determination and viral entry, we report a cryo-electron microscopy (cryo-EM) structure of the SADS-CoV S trimer in the prefusion conformation at a 3.55-Å resolution. Our structure reveals that the SADS-CoV S trimer assumes an intrasubunit quaternary packing mode in which the S1 subunit N-terminal domain (S1-NTD) and the S1 subunit C-terminal domain (S1-CTD) of the same protomer pack together by facing each other in the lying-down state. SADS-CoV S has several distinctive structural features that may facilitate immune escape, such as a relatively compact architecture of the S trimer and epitope masking by glycan shielding. Comparison of SADS-CoV S with the spike proteins of the other coronavirus genera suggested that the structural features of SADS-CoV S are evolutionarily related to those of the spike proteins of the other genera rather than to the spike protein of a typical alphacoronavirus. These data provide new insights into the evolutionary relationship between spike glycoproteins of SADS-CoV and those of other coronaviruses and extend our understanding of their structural and functional diversity. IMPORTANCE In this article, we report the atomic-resolution prefusion structure of the spike protein from swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV is a pathogenic alphacoronavirus that was responsible for a large-scale outbreak of fatal disease in pigs and that was reported to be capable of interspecies transmission. We describe the overall structure of the SADS-CoV spike protein and conducted a detailed analysis of its main structural elements. Our results and analyses are consistent with those of previous phylogenetic studies and suggest that the SADS-CoV spike protein is evolutionarily related to the spike proteins of betacoronaviruses, with a strong similarity in S1-NTDs and a marked divergence in S1-CTDs. Moreover, we discuss the possible immune evasion strategies used by the SADS-CoV spike protein. Our study provides insights into the structure and immune evasion strategies of the SADS-CoV spike protein and broadens the understanding of the evolutionary relationships between coronavirus spike proteins of different genera.

scholarly journals The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13

2020 ◽  
Author(s):  
Shufeng Liu ◽  
Prabhuanand Selvaraj ◽  
Christopher Z. Lien ◽  
Wells W. Wu ◽  
Chao-Kai Chou ◽  
...  
Keyword(s):  
Animal Species ◽  
Cell Types ◽  
Spike Protein ◽  
Diverse Range ◽  
Host Tropism ◽  
Cellular Tropism ◽  
Horseshoe Bat ◽  
Different Cell Types ◽  
Spike Proteins

SummaryBiochemical and structural analyses suggest that SARS-CoV-2 is well-adapted to infecting human and the presence of four residues (PRRA) at the S1/S2 site within the Spike protein may lead to unexpected tissue or host tropism. Here we report that SARS-CoV-2 efficiently utilized ACE2 of 9 species except mouse to infect 293T cells. Similarly, pseudoviruses bearing spike protein derived from either the bat raTG13 or pangolin GX, two closely related animal coronaviruses, utilized ACE2 of a diverse range of animal species to gain entry. Removal of PRRA from SARS-CoV-2 Spike displayed distinct effects on pseudoviral entry into different cell types. Strikingly, insertion of PRRA into the raTG13 Spike selectively abrogated the usage of horseshoe bat and pangolin ACE2 but conferred usage of mouse ACE2 by the relevant pseudovirus to enter cells. Together, our findings identified a previously unrecognized effect of the PRRA insert on SARS-CoV-2 and raTG13 spike proteins.

scholarly journals Blocking SARS-CoV-2 Spike Protein binding to ACE2 receptor through Narcotinic Compounds Combined with Adjuvants: an in silico Insight

2021 ◽  
Author(s):  
Saeedeh Mohammadi ◽  
Ayoub Esmailpour ◽  
Nader Sakhaee ◽  
Esmail Doustkhah
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Muramyl Dipeptide ◽  
Docking Studies ◽  
Spike Protein ◽  
Binding Affinities ◽  
Narcotic Analgesics ◽  
S Protein ◽  
Suitable Combination ◽  
Spike Proteins

Abstract Protein products of SARS-CoV-2 spike (S) coding gene sequence, were all analyzed and compared to other SARS-CoV S proteins to elucidate structural similarities of spike proteins. A homology modeling of SARS-CoV-2 S protein was obtained and used in molecular docking studies to find binding affinities of spike protein for angiotensin-converting enzyme 2 (ACE2). The two most important binding sites of S protein, namely, RBD and CTD, critically responsible for binding interactions, were identified. Finally, binding affinity of RBD and CTD domains of S protein with narcotic analgesics are studied. Moreover, interactions of ACE2 receptor- S protein with narcotic compounds when mixed with small molecule adjuvants to improve the immune response and increase the efficacy of potential vaccines, were taken into consideration. In-silico results suggest that the combination of narcotine hemiacetal with mannide monooleate shows a stronger binding affinity with CTD, while carprofen-muramyl dipeptide and squalene have stronger binding affinities for the RBD portion of S protein. Thus, a suitable combination of these narcotic is proposed to yield potent site-blocking efficacy for ACE2 receptor against SARS-CoV-2 spike proteins.

Discovery of Some Antiviral Natural products to fight against Novel Corona Virus (SARS-CoV-2) using Insilico approach

2020 ◽  
Vol 23 ◽  
Author(s):  
Ashish Shah ◽  
Vaishali Patel ◽  
Bhumika Parmar
Keyword(s):  
Binding Affinity ◽  
Protein S ◽  
Docking Studies ◽  
Spike Protein ◽  
Enveloped Viruses ◽  
Bioactivity Prediction ◽  
Corona Virus ◽  
Main Protease ◽  
Antiviral Activities ◽  
Deadly Disease

Background: Novel Corona virus is a type of enveloped viruses with a single stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. Objective: We had selected 30 phytoconstituents from the different plants which are reported for antiviral activities against corona virus (CoVs) and performed insilico screening to find out phytoconstituents which have potency to inhibit specific target of novel corona virus. Methods: We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. Results: We had screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin using insilico approach. All compounds found safe in insilico toxicity studies. Bioactivity prediction reviles that these all compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had higher binding affinity for the target PLpro and Spike protein. Conclusion: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

scholarly journals A Single Adaptive Mutation in Sodium Taurocholate Cotransporting Polypeptide Induced by Hepadnaviruses Determines Virus Species Specificity

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Junko S. Takeuchi ◽  
Kento Fukano ◽  
Masashi Iwamoto ◽  
Senko Tsukuda ◽  
Ryosuke Suzuki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Virus Infection ◽  
Positive Selection ◽  
Sodium Taurocholate ◽  
Arms Race ◽  
Adaptive Mutation ◽  
Molecular Evidence ◽  
Adaptive Mutations ◽  
Wide Range ◽  
Coevolutionary Arms Race

ABSTRACTHepatitis B virus (HBV) and its hepadnavirus relatives infect a wide range of vertebrates, from fish to human. Hepadnaviruses and their hosts have a long history of acquiring adaptive mutations. However, there are no reports providing direct molecular evidence for such a coevolutionary “arms race” between hepadnaviruses and their hosts. Here, we present evidence suggesting that the adaptive evolution of the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, has been influenced by virus infection. Evolutionary analysis of the NTCP-encoding genes from 20 mammals showed that most NTCP residues are highly conserved among species, exhibiting evolution under negative selection (dN/dSratio [ratio of nonsynonymous to synonymous evolutionary changes] of <1); this observation implies that the evolution of NTCP is restricted by maintaining its original protein function. However, 0.7% of NTCP amino acid residues exhibit rapid evolution under positive selection (dN/dSratio of >1). Notably, a substitution at amino acid (aa) 158, a positively selected residue, converting the human NTCP to a monkey-type sequence abrogated the capacity to support HBV infection; conversely, a substitution at this residue converting the monkey Ntcp to the human sequence was sufficient to confer HBV susceptibility. Together, these observations suggested a close association of the aa 158 positive selection with the pressure by virus infection. Moreover, the aa 158 sequence determined attachment of the HBV envelope protein to the host cell, demonstrating the mechanism whereby HBV infection would create positive selection at this NTCP residue. In summary, we provide the first evidence in agreement with the function of hepadnavirus as a driver for inducing adaptive mutation in host receptor.IMPORTANCEHBV and its hepadnavirus relatives infect a wide range of vertebrates, with a long infectious history (hundreds of millions of years). Such a long history generally allows adaptive mutations in hosts to escape from infection while simultaneously allowing adaptive mutations in viruses to overcome host barriers. However, there is no published molecular evidence for such a coevolutionary arms race between hepadnaviruses and hosts. In the present study, we performed coevolutionary phylogenetic analysis between hepadnaviruses and the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, combined with virological experimental assays for investigating the biological significance of NTCP sequence variation. Our data provide the first molecular evidence supporting that HBV-related hepadnaviruses drive adaptive evolution in the NTCP sequence, including a mechanistic explanation of how NTCP mutations determine host viral susceptibility. Our novel insights enhance our understanding of how hepadnaviruses evolved with their hosts, permitting the acquisition of strong species specificity.

scholarly journals Coevolving Predator and Prey Robots: Do “Arms Races” Arise in Artificial Evolution?

1998 ◽  
Vol 4 (4) ◽  
pp. 311-335 ◽  
Author(s):  
Stefano Nolfi ◽  
Dario Floreano
Keyword(s):  
Evolutionary Robotics ◽  
Arms Race ◽  
Artificial Evolution ◽  
Arms Races ◽  
Wide Range ◽  
Evolutionary Arms Race ◽  
Adaptive Power ◽  
Competing Populations

Coevolution (i.e., the evolution of two or more competing populations with coupled fitness) has several features that may potentially enhance the power of adaptation of artificial evolution. In particular, as discussed by Dawkins and Krebs [3], competing populations may reciprocally drive one another to increasing levels of complexity by producing an evolutionary “arms race.” In this article we will investigate the role of coevolution in the context of evolutionary robotics. In particular, we will try to understand in what conditions coevolution can lead to “arms races.” Moreover, we will show that in some cases artificial coevolution has a higher adaptive power than simple evolution. Finally, by analyzing the dynamics of coevolved populations, we will show that in some circumstances well-adapted individuals would be better advised to adopt simple but easily modifiable strategies suited for the current competitor strategies rather than incorporate complex and general strategies that may be effective against a wide range of opposing counter-strategies.

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