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1.
Viruses ; 14(12):2764, 2022.
Article in English | MDPI | ID: covidwho-2155319

ABSTRACT

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of the initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track the virus's genetic changes that drive the early evolutionary dynamics of the Omicron. Based on the Omicron dataset chosen for the improved temporal signals and sampled globally between November 2021 and January 2022, the most recent common ancestor (tMRCA) and substitution rates for BA.1 were estimated to be that of 18 September 2021 (95% highest posterior density (HPD), 4 August-22 October 2021) and 1.435 ×10-3 (95% HPD =  1.021 ×10-3 - 1.869 ×10-3) substitution/site/year, respectively, whereas 3 November 2021 (95% highest posterior density (HPD) 26 September-28 November 2021) and 1.074 ×10-3 (95% HPD =  6.444 ×10-4 - 1.586 ×10-3) substitution/site/year were estimated for the BA.2 sub-lineage. The findings of this study suggest that the Omicron BA.1 and BA.2 sub-lineages originated independently and evolved over time. Furthermore, we identified multiple sites in the spike protein undergoing continued diversifying selection that may alter the neutralization profile of BA.1. This study sheds light on the ongoing global genomic surveillance and Bayesian molecular dating analyses to better understand the evolutionary dynamics of the virus and, as a result, mitigate the impact of emerging variants on public health.

2.
Methods in Microbiology ; 2022.
Article in English | ScienceDirect | ID: covidwho-1821091

ABSTRACT

Since the beginning of the COVID-19 pandemic, many diagnostic approaches (RT-qPCR, RAPID, LFA) have been adopted, with RT-qPCR being the most popular/gold standard. But, one of the major problems of COVID-19 diagnostics is the presentation of a wide range of symptoms which varies among different patients and needs early diagnosis for better management. Even though RT-qPCR is a precise molecular technique false negative results may be obtained. On the other hand, CRISPR-based SARS-CoV-2 detection approaches are cost and time efficient, highly sensitive and specific, and do not require sophisticated instruments. Moreover, they also show promise for increased scalability and diagnostic tests can be carried out at the point-of-care (POC). The CRISPR can be customized to the target of any genomic region of interest within the desired genome possessing a broad range of other applications and has been efficiently implemented for diagnosis of SARS-CoV-2. The CRISPR/Cas systems provide the specific gene targeting with immense potential to develop new generation diagnostics and therapeutics. Moreover, with the CRISPR/Cas based therapeutics, multiplexing is possible, where different sgRNAs or crRNAs can be guided to more than one target within the same gene thus decreasing the possibility of viral escape mutants. As an exceptionally efficient tool CRISPR/Cas13 and CARVER (Cas13-assisted restriction of viral expression and readout) systems can be implemented to target a broad range of ssRNA viruses that can be used for both, diagnosis and treatment for a variety of viral diseases including SARS-CoV-2. However, the efficacy and safety of the CRISPR-based therapeutics needs to be assessed in pre-clinical and clinical settings. Although the CRISPR biotechnologies are not very helpful to control the present pandemic of COVID-19 it is hopeful that the limitations of the CRISPR/Cas system can be overcome in the near future. The CRISPR based strategies may lead to a new era in the field of disease diagnosis and therapeutic development that would make us better prepared for future viral threats.

3.
Environ Res ; 212(Pt C): 113303, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1796871

ABSTRACT

Understanding the origin of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a highly debatable and unresolved issue for scientific communities all over the world. Understanding the mechanism of virus entry to the host cells is crucial to deciphering the susceptibility profiles of animal species to SARS-CoV-2. The interaction of SARS-CoV-2 ligands (receptor-binding domain on spike protein) with its host cell receptor, angiotensin-converting enzyme 2 (ACE2), is a critical determinant of host range and cross-species transmission. In this study, we developed and implemented a rigorous computational approach for predicting binding affinity between 299 ACE2 orthologs from diverse vertebrate species and the SARS-CoV-2 spike protein. The findings show that the SARS-CoV-2 spike protein can bind to a wide range of vertebrate species carrying evolutionary divergent ACE2, implying a broad host range at the virus entry level, which may contribute to cross-species transmission and further viral evolution. Furthermore, the current study facilitated the identification of genetic determinants that may differentiate susceptible from resistant host species based on the conservation of ACE2-spike protein interacting residues in vertebrate host species known to facilitate SARS-CoV-2 infection; however, these genetic determinants warrant in vivo experimental confirmation. The molecular interactions associated with varied binding affinity of distinct ACE2 isoforms in a specific bat species were identified using protein structure analysis, implying the existence of diversified bat species' susceptibility to SARS-CoV-2. The current study's findings highlight the importance of intensive surveillance programmes aimed at identifying susceptible hosts, especially those with the potential to transmit zoonotic pathogens, in order to prevent future outbreaks.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Angiotensin-Converting Enzyme 2 , Animals , Humans , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vertebrates/metabolism
4.
Rev Med Virol ; 31(5): 1-11, 2021 09.
Article in English | MEDLINE | ID: covidwho-1574954

ABSTRACT

The clinical severity, rapid transmission and human losses due to coronavirus disease 2019 (Covid-19) have led the World Health Organization to declare it a pandemic. Traditional epidemiological tools are being significantly complemented by recent innovations especially using artificial intelligence (AI) and machine learning. AI-based model systems could improve pattern recognition of disease spread in populations and predictions of outbreaks in different geographical locations. A variable and a minimal amount of data are available for the signs and symptoms of Covid-19, allowing a composite of maximum likelihood algorithms to be employed to enhance the accuracy of disease diagnosis and to identify potential drugs. AI-based forecasting and predictions are expected to complement traditional approaches by helping public health officials to select better response and preparedness measures against Covid-19 cases. AI-based approaches have helped address the key issues but a significant impact on the global healthcare industry is yet to be achieved. The capability of AI to address the challenges may make it a key player in the operation of healthcare systems in future. Here, we present an overview of the prospective applications of the AI model systems in healthcare settings during the ongoing Covid-19 pandemic.


Subject(s)
Artificial Intelligence , COVID-19/epidemiology , Delivery of Health Care , Humans , Pandemics
5.
Viruses ; 13(9)2021 09 16.
Article in English | MEDLINE | ID: covidwho-1411085

ABSTRACT

Many viruses that cause serious diseases in humans and animals, including the betacoronaviruses (beta-CoVs), such as SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2, have natural reservoirs in bats. Because these viruses rely entirely on the host cellular machinery for survival, their evolution is likely to be guided by the link between the codon usage of the virus and that of its host. As a result, specific cellular microenvironments of the diverse hosts and/or host tissues imprint peculiar molecular signatures in virus genomes. Our study is aimed at deciphering some of these signatures. Using a variety of genetic methods we demonstrated that trends in codon usage across chiroptera-hosted CoVs are collaboratively driven by geographically different host-species and temporal-spatial distribution. We not only found that chiroptera-hosted CoVs are the ancestors of SARS-CoV-2, but we also revealed that SARS-CoV-2 has the codon usage characteristics similar to those seen in CoVs infecting the Rhinolophus sp. Surprisingly, the envelope gene of beta-CoVs infecting Rhinolophus sp., including SARS-CoV-2, had extremely high CpG levels, which appears to be an evolutionarily conserved trait. The dissection of the furin cleavage site of various CoVs infecting hosts revealed host-specific preferences for arginine codons; however, arginine is encoded by a wider variety of synonymous codons in the murine CoV (MHV-A59) furin cleavage site. Our findings also highlight the latent diversity of CoVs in mammals that has yet to be fully explored.


Subject(s)
Chiroptera/virology , Codon Usage , Coronavirus/genetics , Evolution, Molecular , Animals , Furin/metabolism , Genetic Variation , Genome, Viral
6.
Brief Bioinform ; 22(2): 1006-1022, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1387712

ABSTRACT

Interaction of SARS-CoV-2 spike glycoprotein with the ACE2 cell receptor is very crucial for virus attachment to human cells. Selected mutations in SARS-CoV-2 S-protein are reported to strengthen its binding affinity to mammalian ACE2. The N501T mutation in SARS-CoV-2-CTD furnishes better support to hotspot 353 in comparison with SARS-CoV and shows higher affinity for receptor binding. Recombination analysis exhibited higher recombination events in SARS-CoV-2 strains, irrespective of their geographical origin or hosts. Investigation further supports a common origin among SARS-CoV-2 and its predecessors, SARS-CoV and bat-SARS-like-CoV. The recombination events suggest a constant exchange of genetic material among the co-infecting viruses in possible reservoirs and human hosts before SARS-CoV-2 emerged. Furthermore, a comprehensive analysis of codon usage bias (CUB) in SARS-CoV-2 revealed significant CUB among the S-genes of different beta-coronaviruses governed majorly by natural selection and mutation pressure. Various indices of codon usage of S-genes helped in quantifying its adaptability in other animal hosts. These findings might help in identifying potential experimental animal models for investigating pathogenicity for drugs and vaccine development experiments.


Subject(s)
Biological Evolution , Codon Usage , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Humans , Models, Animal , Mutation , RNA, Transfer/genetics , Spike Glycoprotein, Coronavirus/metabolism
7.
Pathogens ; 9(7)2020 06 28.
Article in English | MEDLINE | ID: covidwho-622889

ABSTRACT

The technology-driven world of the 21st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2') within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures.

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