Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 277
Filter
1.
Chin Med J (Engl) ; 135(10): 1213-1222, 2022 May 20.
Article in English | MEDLINE | ID: covidwho-2190861

ABSTRACT

ABSTRACT: The pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to major public health challenges globally. The increasing viral lineages identified indicate that the SARS-CoV-2 genome is evolving at a rapid rate. Viral genomic mutations may cause antigenic drift or shift, which are important ways by which SARS-CoV-2 escapes the human immune system and changes its transmissibility and virulence. Herein, we summarize the functional mutations in SARS-CoV-2 genomes to characterize its adaptive evolution to inform the development of vaccination, treatment as well as control and intervention measures.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation/genetics , Pandemics , SARS-CoV-2/genetics , Virulence
2.
Viruses ; 14(11)2022 Nov 21.
Article in English | MEDLINE | ID: covidwho-2123864

ABSTRACT

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Cricetinae , Mice , Animals , Humans , SARS-CoV-2/genetics , Mice, Inbred C57BL , Virulence , Disease Models, Animal , Antiviral Agents
3.
Viruses ; 14(11)2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2123861

ABSTRACT

The porcine epidemic diarrhea virus (PEDV) is a member of the coronavirus family, causing deadly watery diarrhea in newborn piglets. The global pandemic of PEDV, with significant morbidity and mortality, poses a huge threat to the swine industry. The currently developed vaccines and drugs are only effective against the classic GI strains that were prevalent before 2010, while there is no effective control against the GII variant strains that are currently a global pandemic. In this review, we summarize the latest progress in the biology of PEDV, including its transmission and origin, structure and function, evolution, and virus-host interaction, in an attempt to find the potential virulence factors influencing PEDV pathogenesis. We conclude with the mechanism by which PEDV components antagonize the immune responses of the virus, and the role of host factors in virus infection. Essentially, this review serves as a valuable reference for the development of attenuated virus vaccines and the potential of host factors as antiviral targets for the prevention and control of PEDV infection.


Subject(s)
Coronavirus Infections , Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Swine , Virulence , Host Microbial Interactions , Coronavirus Infections/epidemiology , Coronavirus Infections/veterinary , Vaccines, Attenuated
4.
Cells ; 11(22)2022 Nov 14.
Article in English | MEDLINE | ID: covidwho-2115964

ABSTRACT

COVID-19 (coronavirus disease 2019) is a threatening disease caused by the novel enveloped, positive-sense, single-stranded RNA beta-coronavirus, denoted as SARS-CoV-2 [...].


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Virulence , RNA , Disease Outbreaks
5.
Chem Biol Interact ; 368: 110244, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2095126

ABSTRACT

Interactions between the human angiotensin-converting enzyme 2 (ACE2) and the RBD region of the SARS-CoV-2 Spike protein are critical for virus entry into the host cell. The objective of this work was to identify some of the most relevant SARS-CoV-2 Spike variants that emerged during the pandemic and evaluate their binding affinity with human variants of ACE2 since some ACE2 variants can enhance or reduce the affinity of the interaction between the ACE2 and S proteins. However, no information has been sought to extrapolate to different variants of SARS-CoV-2. Therefore, to understand the impact on the affinity of the interaction between ACE2 protein variants and SARS-CoV-2 protein S variants, molecular docking was used in this study to predict the effects of five mutations of ACE2 when they interact with Alpha, Beta, Delta, Omicron variants and a hypothetical variant, which present mutations in the RBD region of the SARS-CoV-2 Spike protein. Our results suggest that these variants could alter the interaction of the Spike and the human ACE2 protein, losing or creating new inter-protein contacts, enhancing viral fitness by improving binding affinity, and leading to an increase in infectivity, virulence, and transmission. This investigation highlighted that the S19P mutation of ACE2 decreases the binding affinity between the ACE2 and Spike proteins in the presence of the Beta variant and the wild-type variant of SARS-CoV-2 isolated in Wuhan-2019. The R115Q mutation of ACE2 lowers the binding affinity of these two proteins in the presence of the Beta and Delta variants. Similarly, the K26R mutation lowers the affinity of the interaction between the ACE2 and Spike proteins in the presence of the Alpha variant. This decrease in binding affinity is probably due to the lack of interaction between some of the key residues of the interaction complex between the ACE2 protein and the RBD region of the SARS-CoV-2 Spike protein. Therefore, ACE2 mutations appear in the presence of these variants, they could suggest an intrinsic resistance to COVID-19 disease. On the other hand, our results suggested that the K26R, M332L, and K341R mutations of ACE2 expressively showed the affinity between the ACE2 and Spike proteins in the Alpha, Beta, and Delta variants. Consequently, these ACE2 mutations in the presence of the Alpha, Beta, and delta variants of SARS-CoV-2 could be more infectious and virulent in human cells compared to the SARS-CoV-2 isolated in Wuhan-2019 and it could have a negative prognosis of the disease. Finally, the Omicron variant in interaction with ACE2 WT, S19P, R115Q, M332L, and K341R mutations of ACE2 showed a significant decrease in binding affinity. This could be consistent that the Omicron variant causes less severe symptoms than previous variants. On the other hand, our results suggested Omicron in the complex with K26R, the binding affinity is increased between ACE2/RBD, which could indicate a negative prognosis of the disease in people with these allelic conditions.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Molecular Docking Simulation , Mutation , Peptidyl-Dipeptidase A/chemistry , Protein Binding , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism , Virulence/genetics
6.
Arch Virol ; 167(11): 2249-2262, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2075433

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an enteric virus that was first identified in 2012. Although PDCoV has been detected worldwide, there is little information about its circulation in western China. In this study, fecal samples were collected from piglets with watery diarrhea in western China between 2015 and 2018 for the detection of PDCoV. The positive rate was 29.9%. A PDCoV strain (CHN/CQ/BN23/2016, BN23) was isolated and selected for further investigation. Phylogenetic analysis showed that this strain formed an individual cluster between the early Chinese lineage and the Chinese lineage. RDP4 and SimPlot analysis demonstrated that strain BN23 is a recombinant of Thailand/S5015L/2015 and CHN-AH-2004. The pathogenicity of BN23 was evaluated in 3-day-old piglets. Challenged piglets developed serious clinical signs and died at 3 days post-inoculation. Our data show that PDCoV is prevalent in western China and that strain BN23 is highly pathogenic to newborn piglets. Therefore, more attention should be paid to emerging PDCoV strains in western China.


Subject(s)
Deltacoronavirus , Animals , China , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Deltacoronavirus/genetics , Deltacoronavirus/isolation & purification , Deltacoronavirus/pathogenicity , Diarrhea/veterinary , Genomics , Phylogeny , Swine , Swine Diseases/virology , Virulence
7.
J Virol ; 96(17): e0096122, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2053119

ABSTRACT

Omicron (B.1.1.529) is the most recent SARS-CoV-2 variant of concern, which emerged in late 2021 and rapidly achieved global predominance by early 2022. In this study, we compared the infection dynamics, tissue tropism, and pathogenesis and pathogenicity of SARS-CoV-2 D614G (B.1), Delta (B.1.617.2), and Omicron BA.1.1 (B.1.1.529) variants in a highly susceptible feline model of infection. Although D614G- and Delta-inoculated cats became lethargic and showed increased body temperatures between days 1 and 3 postinfection (pi), Omicron-inoculated cats remained subclinical and, similar to control animals, gained weight throughout the 14-day experimental period. Intranasal inoculation of cats with D614G- and the Delta variants resulted in high infectious virus shedding in nasal secretions (up to 6.3 log10 TCID50.Ml-1), whereas strikingly lower level of viruses shedding (<3.1 log10 TCID50.Ml-1) was observed in Omicron-inoculated animals. In addition, tissue distribution of the Omicron variant was markedly reduced in comparison to the D614G and Delta variants, as evidenced by lower in situ viral RNA detection, in situ viral immunofluorescence staining, and viral loads in tissues on days 3, 5, and 14 pi. Nasal turbinate, trachea, and lung were the main-but not the only-sites of replication for all three viral variants. However, only scarce virus staining and lower viral titers suggest lower levels of viral replication in tissues from Omicron-infected animals. Notably, while D614G- and Delta-inoculated cats presented pneumonia, histologic examination of the lungs from Omicron-infected cats revealed mild to modest inflammation. Together, these results demonstrate that the Omicron variant BA.1.1 is less pathogenic than D614G and Delta variants in a highly susceptible feline model. IMPORTANCE The SARS-CoV-2 Omicron (B.1.1.529) variant of concern emerged in South Africa late in 2021 and rapidly spread across the world causing a significant increase in the number of infections. Importantly, this variant was also associated with an increased risk of reinfections. However, the number of hospitalizations and deaths due to COVID-19 did not follow the same trends. These early observations suggested effective protection conferred by immunizations and/or overall lower virulence of the highly mutated variant virus. In this study we present novel evidence demonstrating that the Omicron BA.1.1 variant of concern presents a lower pathogenicity when compared to D614G- or Delta variants in cats. Clinical, virological, and pathological evaluations revealed lower disease severity, viral replication, and lung pathology in Omicron-infected cats when compared with D614G and Delta variant inoculated animals, confirming that Omicron BA.1.1 is less pathogenic in a highly susceptible feline model of infection.


Subject(s)
COVID-19/virology , SARS-CoV-2 , Animals , Cats , Disease Models, Animal , Humans , SARS-CoV-2/pathogenicity , Virulence , Virus Replication
9.
Mol Genet Genomics ; 297(6): 1741-1754, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2035055

ABSTRACT

The current pandemic (COVID-19) has made evident the need to approach pathogenicity from a deeper and more systematic perspective that might lead to methodologies to quickly predict new strains of microbes that could be pathogenic to humans. Here we propose as a solution a general and principled definition of pathogenicity that can be practically implemented in operational ways in a framework for characterizing and assessing the (degree of) potential pathogenicity of a microbe to a given host (e.g., a human individual) just based on DNA biomarkers, and to the point of predicting its impact on a host a priori to a meaningful degree of accuracy. The definition is based on basic biochemistry, the Gibbs free Energy of duplex formation between oligonucleotides and some deep structural properties of DNA revealed by an approximation with certain properties. We propose two operational tests based on the nearest neighbor (NN) model of the Gibbs Energy and an approximating metric (the h-distance.) Quality assessments demonstrate that these tests predict pathogenicity with an accuracy of over 80%, and sensitivity and specificity over 90%. Other tests obtained by training machine learning models on deep features extracted from DNA sequences yield scores of 90% for accuracy, 100% for sensitivity and 80% for specificity. These results hint towards the possibility of an operational, objective, and general conceptual framework for prior identification of pathogens and their impact without the cost of death or sickness in a host (e.g., humans.) Consequently, a reasonable prediction of possible pathogens might pave the way to eventually transform the way we handle and prepare for future pandemic events and mitigate the adverse impact on human health, while reducing the number of clinical trials to obtain similar results.


Subject(s)
COVID-19 , Humans , Virulence/genetics , Oligonucleotides , DNA , Biomarkers
10.
Lung ; 200(5): 573-577, 2022 10.
Article in English | MEDLINE | ID: covidwho-2035047

ABSTRACT

In vitro and animal models described lower replication capacity and virulence of SARS-CoV-2 Omicron lineage in lower respiratory airways compared to wild type and other variants of concern (oVOCs). Among adult subjects admitted to our hospital (Turin, Italy) due to wild type, oVOCs, and Omicron SARS-CoV-2-related pneumonia (n = 100 for each lineage), the cases of Omicron pneumonia showed lower degree of lung parenchyma involvement (aß -1.471, p = 0.037), less tendency to parenchyma consolidation (aOR 0.500, p = 0.011), and better respiratory functions (assessed by ambient air arterial blood gas analysis). After adjusting for demographic, previous immunity, and comorbidities, Omicron pneumonia still associated with lower risk of respiratory failure (for severe respiratory failure, Wild-type versus Omicron aOR 15.6, p = 0.005 and oVOCs versus Omicron aOR 31.7, p < 0.001). These observations are in line with preliminary findings from in vitro and animal models and could explain why Omicron infection has been associated with lower mortality and hospitalization in human.


Subject(s)
COVID-19 , Pneumonia , Respiratory Insufficiency , Animals , Humans , Inpatients , Lung , SARS-CoV-2 , Virulence
11.
Int J Mol Sci ; 23(16)2022 Aug 18.
Article in English | MEDLINE | ID: covidwho-2023740

ABSTRACT

In this work, we analysed human isolates of nontyphoidal Salmonella enterica subsp. enterica (NTS), which were collected from salmonellosis cases in Armenia from 1996 to 2019. This disease became a leading food-borne bacterial infection in the region, with the younger age groups especially affected. The isolates were characterised by serotyping, Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR) typing, and whole genome sequencing (WGS). The main serotypes were S. Typhimurium, S. Enteritidis, and S. Arizonae. ERIC-PCR indicated a high degree of clonality among S. Typhimurium strains, which were also multidrug-resistant and produced extended spectrum beta-lactamases. During the study period, the frequency of S. Typhimurium and S. Arizonae isolations decreased, but with the increase in S. Enteritidis and other NTS. A total of 42 NTS isolates were subjected to WGS and explored for virulence-related traits and the corresponding genetic elements. Some virulence and genetic factors were shared by all NTS serotypes, while the main differences were attributed to the serotype-specific diversity of virulence genes, SPIs, virulence plasmids, and phages. The results indicated the variability and dynamics in the epidemiology of salmonellosis and a high virulence potential of human NTS isolates circulating in the region.


Subject(s)
Salmonella Infections , Salmonella enterica , Anti-Bacterial Agents , Armenia/epidemiology , Humans , Molecular Epidemiology , Salmonella/genetics , Salmonella Infections/epidemiology , Salmonella Infections/microbiology , Salmonella enterica/genetics , Virulence/genetics
12.
Microbiol Spectr ; 10(5): e0226322, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2019798

ABSTRACT

We investigated the distribution, virulence, and pathogenic characteristics of mutated SARS-CoV-2 to clarify the association between virulence and the viral spreading ability of current and future circulating strains. Chinese rhesus macaques were infected with ancestral SARS-CoV-2 strain GD108 and Beta variant B.1.351 (B.1.351) and assessed for clinical signs, viral distribution, pathological changes, and pulmonary inflammation. We found that GD108 replicated more efficiently in the upper respiratory tract, whereas B.1.351 replicated more efficiently in the lower respiratory tract and lung tissue, implying a reduced viral shedding and spreading ability of B.1.351 compared with that of GD108. Importantly, B.1.351 caused more severe lung injury and dramatically elevated the level of inflammatory cytokines compared with those observed after infection with GD108. Moreover, both B.1.351 and GD108 induced spike-specific T-cell responses at an early stage of infection, with higher levels of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in the B.1.351 group and higher levels of interleukin 17 (IL-17) in the GD108 group, indicating a divergent pattern in the T-cell-mediated inflammatory "cytokine storm." This study provides a basis for exploring the pathogenesis of SARS-CoV-2 variants of concern (VOCs) and establishes an applicable animal model for evaluating the efficacy and safety of vaccines and drugs. IMPORTANCE One of the priorities of the current SARS-CoV-2 vaccine and drug research strategy is to determine the changes in transmission ability, virulence, and pathogenic characteristics of SARS-CoV-2 variants. In addition, nonhuman primates (NHPs) are suitable animal models for the study of the pathogenic characteristics of SARS-CoV-2 and could contribute to the understanding of pathogenicity and transmission mechanisms. As SARS-CoV-2 variants continually emerge and the viral biological characteristics change frequently, the establishment of NHP infection models for different VOCs is urgently needed. In the study, the virulence and tissue distribution of B.1.351 and GD108 were comprehensively studied in NHPs. We concluded that the B.1.351 strain was more virulent but exhibited less viral shedding than the latter. This study provides a basis for determining the pathogenic characteristics of SARS-CoV-2 and establishes an applicable animal model for evaluating the efficacy and safety of vaccines and drugs.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , SARS-CoV-2/genetics , Interleukin-17 , Virus Shedding , Virulence , COVID-19 Vaccines , Tumor Necrosis Factor-alpha , Macaca mulatta , Interferon-gamma , Disease Models, Animal
13.
Proc Natl Acad Sci U S A ; 119(37): e2204717119, 2022 09 13.
Article in English | MEDLINE | ID: covidwho-2017032

ABSTRACT

The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the spike protein. Although these differences in spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome that may also affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through interference with innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other nonspike mutations on SARS-CoV-2 pathogenesis, we synthesized both viruses possessing deletions in the accessory genes as well as viruses where the WA-1 spike is replaced by each variant spike gene in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to both WA-1 and the full variant viruses. Our work has revealed that the accessory proteins contribute to SARS-CoV-2 pathogenesis and the nonspike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host. This work suggests that while spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may alter clinical disease presentation.


Subject(s)
COVID-19 , Mutation , SARS-CoV-2 , Viral Regulatory and Accessory Proteins , Virulence , COVID-19/virology , Humans , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Viral Regulatory and Accessory Proteins/genetics , Virulence/genetics , Virus Replication/genetics
14.
Cell Rep Med ; 3(9): 100743, 2022 09 20.
Article in English | MEDLINE | ID: covidwho-2004613

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 was a dominant circulating SARS-CoV-2 variant worldwide. Recent reports hint that BA.2 is similarly potent regarding antibody evasion but may be more transmissible than BA.1. The pathogenicity of BA.2 remains unclear and is of critical public health significance. Here we investigated the virological features and pathogenicity of BA.2 with in vitro and in vivo models. We show that BA.2 is less dependent on transmembrane protease serine 2 (TMPRSS2) for virus entry in comparison with BA.1 in vitro. In K18-hACE2 mice, BA.2 replicates more efficiently than BA.1 in the nasal turbinates and replicates marginally less efficiently in the lungs, leading to decreased body weight loss and improved survival. Our study indicates that BA.2 is similarly attenuated in lungs compared with BA.1 but is potentially more transmissible because of its better replication at the nasal turbinates.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , Mice , SARS-CoV-2/genetics , Serine , Virulence
15.
Virology ; 575: 36-42, 2022 10.
Article in English | MEDLINE | ID: covidwho-2004599

ABSTRACT

All processes in nature are driven by negative Gibbs energy. Gibbs energy is used by various viruses and their strains to hijack host cell metabolic machinery. The analysis was made by using the atom counting method to obtain elemental compositions and Gibbs energy of growth of the BA.2 strain of SARS-CoV-2. Moreover, Gibbs energy of binding was determined for the BA.2 strain. The properties of BA.2 were compared to those of Hu-1, Delta and Omicron strains. It is concluded that SARS-CoV-2 has evolved by making its Gibbs energy of binding more negative. Hence, it seems that the change in Gibbs energy of binding plays the major role in SARS-CoV-2 evolution. Therefore, Gibbs energy difference between various strains represents the possible mechanism of Darwinian evolution of viruses. In particular, a virus evolves through mutations, resulting in change in information content, elemental composition, increase in infectivity and decrease in pathogenicity.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation , SARS-CoV-2/genetics , Virulence
16.
EBioMedicine ; 80: 104035, 2022 06.
Article in English | MEDLINE | ID: covidwho-2004029
17.
Phys Chem Chem Phys ; 24(34): 20371-20380, 2022 Aug 31.
Article in English | MEDLINE | ID: covidwho-2000945

ABSTRACT

New variants of SARS-CoV-2 are being reported worldwide. The World Health Organization has reported Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529) as the variants of concern. There are speculations that the variants might evade the host immune responses induced by currently available vaccines and develop resistance to drugs under consideration. The first step of viral infection in COVID-19 occurs through the interaction of the spike protein's receptor-binding domain (RBD) with the peptidase domain of the human ACE-2 (hACE-2) receptor. This study aims to get a molecular-level understanding of the mechanism behind the increased infection rate in the alpha variant. We have computationally studied the spike protein interaction in both the wild-type and B.1.1.7 variant with the hACE-2 receptor using molecular dynamics and MM-GBSA based binding free energy calculations. The binding free energy difference shows that the mutant variant of the spike protein has increased binding affinity for the hACE-2 receptor (i.e. ΔG(N501Y,A570D) is in the range -7.2 to -7.6 kcal mol-1) and the results were validated using Density functional theory. We demonstrate that with the use of state-of-the-art computational approaches, we can, in advance, predict the virulent nature of variants of SARS-CoV-2 and alert the world healthcare system.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Spike Glycoprotein, Coronavirus/genetics , Virulence
18.
PLoS One ; 17(8): e0272945, 2022.
Article in English | MEDLINE | ID: covidwho-1993505

ABSTRACT

Streptococcus pneumoniae (S. pneumoniae), the major etiological agent of community-acquired pneumonia (CAP) contributes significantly to the global burden of infectious diseases which is getting resistant day by day. Nearly 30% of the S. pneumoniae genomes encode hypothetical proteins (HPs), and better understandings of these HPs in virulence and pathogenicity plausibly decipher new treatments. Some of the HPs are present across many Streptococcus species, systematic assessment of these unexplored HPs will disclose prospective drug targets. In this study, through a stringent bioinformatics analysis of the core genome and proteome of S. pneumoniae PCS8235, we identified and analyzed 28 HPs that are common in many Streptococcus species and might have a potential role in the virulence or pathogenesis of the bacteria. Functional annotations of the proteins were conducted based on the physicochemical properties, subcellular localization, virulence prediction, protein-protein interactions, and identification of essential genes, to find potentially druggable proteins among 28 HPs. The majority of the HPs are involved in bacterial transcription and translation. Besides, some of them were homologs of enzymes, binding proteins, transporters, and regulators. Protein-protein interactions revealed HP PCS8235_RS05845 made the highest interactions with other HPs and also has TRP structural motif along with virulent and pathogenic properties indicating it has critical cellular functions and might go under unconventional protein secretions. The second highest interacting protein HP PCS8235_RS02595 interacts with the Regulator of chromosomal segregation (RocS) which participates in chromosome segregation and nucleoid protection in S. pneumoniae. In this interacting network, 54% of protein members have virulent properties and 40% contain pathogenic properties. Among them, most of these proteins circulate in the cytoplasmic area and have hydrophilic properties. Finally, molecular docking and dynamics simulation demonstrated that the antimalarial drug Artenimol can act as a drug repurposing candidate against HP PCS8235_RS 04650 of S. pneumoniae. Hence, the present study could aid in drugs against S. pneumoniae.


Subject(s)
Genome, Bacterial , Streptococcus pneumoniae , Bacterial Proteins/metabolism , Molecular Docking Simulation , Streptococcus/genetics , Virulence
19.
Proc Biol Sci ; 289(1978): 20212800, 2022 07 13.
Article in English | MEDLINE | ID: covidwho-1992455

ABSTRACT

Hosts can avoid parasites (and pathogens) by reducing social contact, but such isolation may carry costs, e.g. increased vulnerability to predators. Thus, many predator-host-parasite systems confront hosts with a trade-off between predation and parasitism. Parasites, meanwhile, evolve higher virulence in response to increased host sociality and consequently, increased multiple infections. How does predation shift coevolution of host behaviour and parasite virulence? What if predators are selective, i.e. predators disproportionately capture the sickest hosts? We answer these questions with an eco-coevolutionary model parametrized for a Trinidadian guppy-Gyrodactylus spp. system. Here, increased predation drives host coevolution of higher grouping, which selects for higher virulence. Additionally, higher predator selectivity drives the contact rate higher and virulence lower. Finally, we show how predation and selectivity can have very different impacts on host density and prevalence depending on whether hosts or parasites evolve, or both. For example, higher predator selectivity led to lower prevalence with no evolution or only parasite evolution but higher prevalence with host evolution or coevolution. These findings inform our understanding of diverse systems in which host behavioural responses to predation may lead to increased prevalence and virulence of parasites.


Subject(s)
Parasites , Poecilia , Animals , Biological Evolution , Host-Parasite Interactions , Parasites/physiology , Predatory Behavior , Virulence
20.
Nature ; 609(7929): 994-997, 2022 09.
Article in English | MEDLINE | ID: covidwho-1991628

ABSTRACT

Accurate and timely detection of recombinant lineages is crucial for interpreting genetic variation, reconstructing epidemic spread, identifying selection and variants of interest, and accurately performing phylogenetic analyses1-4. During the SARS-CoV-2 pandemic, genomic data generation has exceeded the capacities of existing analysis platforms, thereby crippling real-time analysis of viral evolution5. Here, we use a new phylogenomic method to search a nearly comprehensive SARS-CoV-2 phylogeny for recombinant lineages. In a 1.6 million sample tree from May 2021, we identify 589 recombination events, which indicate that around 2.7% of sequenced SARS-CoV-2 genomes have detectable recombinant ancestry. Recombination breakpoints are inferred to occur disproportionately in the 3' portion of the genome that contains the spike protein. Our results highlight the need for timely analyses of recombination for pinpointing the emergence of recombinant lineages with the potential to increase transmissibility or virulence of the virus. We anticipate that this approach will empower comprehensive real-time tracking of viral recombination during the SARS-CoV-2 pandemic and beyond.


Subject(s)
COVID-19 , Genome, Viral , Pandemics , Phylogeny , Recombination, Genetic , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , Genome, Viral/genetics , Humans , Mutation , Recombination, Genetic/genetics , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Selection, Genetic/genetics , Spike Glycoprotein, Coronavirus/genetics , Virulence/genetics
SELECTION OF CITATIONS
SEARCH DETAIL