Molecular detection of monkeypox and related viruses: challenges and opportunities.

The recent widespread emergence of monkeypox (mpox), a rare and endemic zoonotic disease by monkeypox virus (MPXV), has made global headlines. While transmissibility (R0 ≈ 0.58) and fatality rate (0-3%) are low, as it causes prolonged morbidity, the World Health Organization has declared monkeypox as a public health emergency of international concern. Thus, effective containment and disease management require quick and efficient detection of MPXV. In this bioinformatic overview, we summarize the numerous molecular tests available for MPXV, and discuss the diversity of genes and primers used in the polymerase chain reaction-based detection. Over 90 primer/probe sets are used for the detection of poxviruses. While hemagglutinin and A-type inclusion protein are the most common target genes, tumor necrosis factor receptor and complement binding protein genes are frequently used for distinguishing Clade I and Clade II of MPXV. Problems and possibilities in the detection of MPXV have been discussed.

Phylogenetic Changes in SARS-CoV-2 Virus in Bosnian-Herzegovinian Population Over the Period of Two Years.

Background: All viral genomes, including the SARS-CoV-2 virus, mutate over time, and some of these mutations can affect the characteristics of the virus, such as the ease of spread, the severity of the patient's clinical picture, or the effect of vaccines, therapeutic drugs, diagnostic tools or other measures of public health and social protection. Because of all the above, it is imperative to carry out continuous sequencing of this pathogen. Objective: The main goal of this research was to obtain the highest quality genomic sequences of the SARS-CoV-2 virus, to compare the obtained sequences with the reference Wuhan-Hu-1 sequence and to obtain a high-quality genomic alignment in order to reconstruct the appropriate phylogenetic tree. Methods: For the purposes of this research, a next-generation semiconductor sequencing method was chosen. In this research, a total of 47 samples of nasopharyngeal and oropharyngeal swabs from patients from the human population of Bosnia and Herzegovina with a clinical diagnosis of COVID-19 were collected. Results: In the processed 47 samples, there are several monophyletic groups on the constructed phylogenetic tree, of which one sample belongs to the same monophyletic group as the Wuhan-Hu-1 reference sequence. Conclusion: The greater number of samples is needed for a more comprehensive approach. Therefore, the results of this research can act as a guideline for the design of effective measures and strategies in order to solve problems regarding future pandemics as efficiently as possible.

Phylogenomic analysis of COVID-19 summer and winter outbreaks in Hong Kong: An observational study.

BACKGROUND: Viral genomic surveillance is vital for understanding the transmission of COVID-19. In Hong Kong, breakthrough outbreaks have occurred in July (third wave) and November (fourth wave) 2020. We used whole viral genome analysis to study the characteristics of these waves. METHODS: We analyzed 509 SARS-CoV-2 genomes collected from Hong Kong patients between 22nd January and 29th November, 2020. Phylogenetic and phylodynamic analyses were performed, and were interpreted with epidemiological information. FINDINGS: During the third and fourth waves, diverse SARS-CoV-2 genomes were identified among imported infections. Conversely, local infections were dominated by a single lineage during each wave, with 96.6% (259/268) in the third wave and 100% (73/73) in the fourth wave belonging to B.1.1.63 and B.1.36.27 lineages, respectively. While B.1.1.63 lineage was imported 2 weeks before the beginning of the third wave, B.1.36.27 lineage has circulated in Hong Kong for 2 months prior to the fourth wave. During the fourth wave, 50.7% (37/73) of local infections in November was identical to the viral genome from an imported case in September. Within B.1.1.63 or B.1.36.27 lineage in our cohort, the most common non-synonymous mutations occurred at the helicase (nsp13) gene. INTERPRETATION: Although stringent measures have prevented most imported cases from spreading in Hong Kong, a single lineage with low-level local transmission in October and early November was responsible for the fourth wave. A superspreading event or lower temperature in November may have facilitated the spread of the B.1.36.27 lineage.

SARS-CoV-2 variant identification using a genome tiling array and genotyping probes.

With over 5.5 million deaths worldwide attributed to the respiratory disease COVID-19 caused by the novel coronavirus SARS-CoV-2, it is essential that continued efforts be made to track the evolution and spread of the virus globally. The authors previously presented a rapid and cost-effective method to sequence the entire SARS-CoV-2 genome with 95% coverage and 99.9% accuracy. This method is advantageous for identifying and tracking variants in the SARS-CoV-2 genome compared with traditional short-read sequencing methods which can be time-consuming and costly. Herein, the addition of genotyping probes to a DNA chip that targets known SARS-CoV-2 variants is presented. The incorporation of genotyping probe sets along with the advent of a moving average filter improved the sequencing coverage and accuracy of the SARS-CoV-2 genome.

Throughout the COVID-19 pandemic the virus known as SARS-CoV-2 has continued to mutate and evolve. It is imperative to continue to track these mutations and where the virus has traveled to best inform healthcare practices and global strategies to combat the virus. The authors previously developed a method to investigate 95% of this viral genome with 99.9% accuracy that was more cost-effective and less time-consuming than previous methods. In this work, specific markers were added to the technology to allow tracking of mutations in the virus that have already been documented. In doing so, the accuracy and how much of the viral genome can be sequenced was improved.

Ribonucleic acid genome mutations induced by the Casimir effect.

In this paper, we investigate the Casimir effect within a virus RNA, particularizing the study to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Then, we discuss the possibility of occurring damage or mutation in its genome due to the presence of quantum vacuum fluctuations inside and around the RNA ribbon. For this, we consider the geometry and the nontrivial topology of the viral RNA as having a simple helical structure. We initially compute the non-thermal Casimir energy associated to that geometry, considering boundary conditions that constrain the zero point oscillations of a massless scalar field to the cylindrical cavity containing a helix pitch of RNA ribbon. Then we extend the obtained result to the electromagnetic field and, following, we calculate the probability of occurring damage or mutation in RNA by using the normalized inverse exponential distribution, which suppresses very low energies, and consider cutoff (threshold) energies corresponding to UV-A and UV-C rays, surely responsible by mutations. Then, by taking into account UV-A, we arrive at a mutation rate per base per infection cycle, which in the case of the SARS-CoV-2 is non-negligible. We find a maximum value of this mutation rate for an RNA ribbon radius, applying it for SARS-CoV-2, in particular. We also calculate a characteristic longitudinal oscillation frequency for the helix pitch value corresponding to the local minimum of the Casimir energy. Finally, we consider thermal fluctuations of classical and quantum nature and show that the corresponding probability of mutation is completely negligible for that virus. Therefore, we conclude that only the nontrivial topology and the geometric attributes of the RNA molecule contribute to the possible mutations caused by quantum vacuum fluctuations in the viral genome.

COVID-19: Some unresolved issues.

Two years after the COVID-19 pandemic, many uncertainties persist about the causal agent, the disease and its future. This document contains the reflection of the COVID-19 working group of the Official College of Physicians of Madrid (ICOMEM) in relation to some questions that remain unresolved. The document includes considerations on the origin of the virus, the current indication for diagnostic tests, the value of severity scores in the onset of the disease and the added risk posed by hypertension or dementia. We also discuss the possibility of deducing viral behavior from the examination of the structure of the complete viral genome, the future of some drug associations and the current role of therapeutic resources such as corticosteroids or extracorporeal oxygenation (ECMO). We review the scarce existing information on the reality of COVID 19 in Africa, the uncertainties about the future of the pandemic and the status of vaccines, and the data and uncertainties about the long-term pulmonary sequelae of those who suffered severe pneumonia.

Favipiravir in SARS-CoV-2 Infection: Is it Worth it?

Favipiravir is a potential antiviral drug undergoing clinical trials to manage various viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Favipiravir possesses antiviral properties against RNA viruses, including SARS-CoV-2. Unfortunately, these viruses do not have authorized antiviral drugs for the management of diseases resulting from their infection, hence the dire need to accentuate the discovery of antiviral drugs that are efficacious and have a broad spectrum. Favipiravir acts primarily by blocking inward and outward movements of the virus from cells. Favipiravir is a prodrug undergoing intracellular phosphorylation and ribosylation to form an active form, favipiravir-RTP, which binds viral RNA-dependent RNA polymerase (RdRp). Considering the novel mechanism of favipiravir action, especially in managing viral infections, it is vital to pay more attention to the promised favipiravir hold in the management of SARS-CoV-2, its efficacy, and dosage regimen, and interactions with other drugs. In conclusion, favipiravir possesses antiviral properties against RNA viruses, including COVID- 19. Favipiravir is effective against SARS-CoV-2 infection through inhibition of RdRp. Pre-clinical and large-scalp prospective studies are recommended for efficacy and long-term safety of favipiravir in COVID-19.

SARS-CoV-2: Next Generation Sequencing and Analysis

Sars-cov-2 is the causative agent responsible for the global pandemic of COVID-19. Bioinformatics tools are used to sequence the viral genome, identify SARS-CoV-2 from all host genomes, and detect its variants. There is no all-in-one tool that can automatically analyse complete sequences, so different bioinformatics resources are needed to work together for detection and characterisation. This paper discusses the use of next-generation sequencing for virus definition and characterization. © 2022 SPIE. All rights reserved.

Defective Interfering Particles with Broad-Acting Antiviral Activity for Dengue, Zika, Yellow Fever, Respiratory Syncytial and SARS-CoV-2 Virus Infection.

More than 100 arboviruses, almost all of which have an RNA genome, cause disease in humans. RNA viruses are causing unprecedented health system challenges worldwide, many with little or no specific therapies or vaccines available. Certain species of mosquito can carry dengue virus (DENV), Zika virus (ZIKV) and yellow fever virus (YFV), where co-infection of these viruses has occurred. Here, we found that purified synthetic defective interfering particles (DIPs) derived from DENV type 2 (DENV-2) strongly suppressed replication of the aforementioned viruses, respiratory syncytial virus (RSV) and also the novel emerging virus SARS-CoV-2 in human cells. DENV DIPs produced in bioreactors, purified by column chromatography, and concentrated are virus-like particles that are about half the diameter of a typical DENV particle, but with similar ratios of the viral structural proteins envelope and capsid. Overall, DIP-treated cells inhibited DENV, ZIKV, YFV, RSV, and SARS-CoV-2 by at least 98% by mechanisms which included interferon (IFN)-dependent cellular antiviral responses. IMPORTANCE DIPs are spontaneously derived virus mutants with deletions in genes that block viral replication. DIPs play important roles in modulation of viral disease, innate immune responses, virus persistence and virus evolution. Here, we investigated the antiviral activity of highly purified synthetic DIPs derived from DENV, which were produced in bioreactors. DENV DIPs purified by column chromatography strongly inhibited five different RNA viruses, including DENV, ZIKV, YFV, RSV, and SARS-CoV-2 in human cells. DENV DIPs inhibited virus replication via delivery of a small, noninfectious viral RNA that activated cellular innate immunity, resulting in robust type 1 interferon responses. The work here presents a pathway for DIP production which is adaptable to Good Manufacturing Practice, so that their preclinical testing should be suitable for evaluation in subjects.

Semantic interoperability: ontological unpacking of a viral conceptual model.

BACKGROUND: Genomics and virology are unquestionably important, but complex, domains being investigated by a large number of scientists. The need to facilitate and support work within these domains requires sharing of databases, although it is often difficult to do so because of the different ways in which data is represented across the databases. To foster semantic interoperability, models are needed that provide a deep understanding and interpretation of the concepts in a domain, so that the data can be consistently interpreted among researchers. RESULTS: In this research, we propose the use of conceptual models to support semantic interoperability among databases and assess their ontological clarity to support their effective use. This modeling effort is illustrated by its application to the Viral Conceptual Model (VCM) that captures and represents the sequencing of viruses, inspired by the need to understand the genomic aspects of the virus responsible for COVID-19. For achieving semantic clarity on the VCM, we leverage the "ontological unpacking" method, a process of ontological analysis that reveals the ontological foundation of the information that is represented in a conceptual model. This is accomplished by applying the stereotypes of the OntoUML ontology-driven conceptual modeling language.As a result, we propose a new OntoVCM, an ontologically grounded model, based on the initial VCM, but with guaranteed interoperability among the data sources that employ it. CONCLUSIONS: We propose and illustrate how the unpacking of the Viral Conceptual Model resolves several issues related to semantic interoperability, the importance of which is recognized by the "I" in FAIR principles. The research addresses conceptual uncertainty within the domain of SARS-CoV-2 data and knowledge.The method employed provides the basis for further analyses of complex models currently used in life science applications, but lacking ontological grounding, subsequently hindering the interoperability needed for scientists to progress their research.

Reinfection with SARS-CoV-2 in a patient undergoing chemotherapy for lymphoma: Case report.

BACKGROUND: COVID-19 is usually a time-limited disease. However, prolonged infections and reinfections can occur among immunocompromised patients. It can be difficult to distinguish a prolonged infection from a new one, especially when reinfection occurs early. METHODS: We report the case of a 57-year-old man infected with SARS-CoV-2 while undergoing chemotherapy for follicular lymphoma. He experienced prolonged symptomatic infection for 3 months despite a 5-day course of remdesivir and eventually deteriorated and died. RESULTS: Viral genome sequencing showed that his final deterioration was most likely due to reinfection. Serologic studies confirmed that the patient did not seroconvert. CONCLUSIONS: This case report highlights that reinfection can occur rapidly (62-67 d) among immunocompromised patients after a prolonged disease. We provide substantial proof of prolonged infection through repeated nucleic acid amplification tests and positive viral culture at day 56 of the disease course, and we put forward evidence of reinfection with viral genome sequencing.

HISTORIQUE: La COVID-19 est généralement une maladie limitée dans le temps. Toutefois, des infections et réinfections prolongées peuvent survenir chez des patients immunodéprimés. Il peut être difficile de distinguer une infection prolongée d'une nouvelle infection, particulièrement lorsque la réinfection se produit rapidement. MÉTHODOLOGIE: Les auteurs rendent compte du cas d'un homme de 57 ans infecté par le SRAS-CoV-2 alors qu'il était sous chimiothérapie pour soigner un lymphome folliculaire. Il a souffert d'une infection symptomatique prolongée de trois mois, malgré un traitement de cinq jours au remdésivir. Son état s'est finalement détérioré et il est décédé. RÉSULTATS: Le séquençage du génome viral a démontré que la détérioration finale de son état a probablement été causée par une réinfection. Les études sérologiques ont confirmé qu'il n'avait pas présenté de séroconversion. CONCLUSIONS: Le présent rapport de cas établit la possibilité d'une réinfection rapide (au bout de 62 à 67 jours) chez les patients immunodéprimés après une longue maladie. Les auteurs fournissent des preuves substantielles d'une infection prolongée par des tests répétés d'amplification des acides nucléiques et par des cultures virales positives au 56e jour de l'évolution de la maladie, et ils présentent des preuves de réinfection grâce au séquençage du génome viral.

Determinative Role of Non-structural Protein Genes in Genus Identification of Coronaviruses

Interrelationship of coronavirus genus with key fragments of viral genome was investigated. Genes of structural proteins (S-gene of spike protein and N-gene of nucleocapsid protein) and ORF1ab of polyprotein pp1ab, that in infected cell is split into 16 non-structural proteins, were considered as such fragments. Statistical method based on averaged codon distribution in the genes of genus prototype variants was applied in the work to recognize genus of coronavirus. High reliability of this method has been demonstrated earlier in recognizing the 15 species and serotypes of the flaviviruses, such as viruses of yellow fever, dengue fever, various encephalitides, etc. For each key fragment of the coronavirus genome the numerical experiments on identification of genus for the 3242 viral genomes from the GenBank have been done. The highest reliability (98%) was achieved, when ORF1ab frequency codon characteristics were used. It appeared to be that in recognizing genus of Gammacoronavirus, basing on spike protein gene, about half of the 345 genomes of this genus were identified as Betacoronavirus (84.6%) and Alphacoronavirus (15.4%). Analogous phenomenon of significant error appeared in determinating Alphacoronavirus genus, basing on nucleocapsid protein gene, also. However, these significant errors may be a consequence of the coronavirus genome plasticity in the result of homologous recombinations between the viral genomes. © 2022 IEEE.

Vaccination Rates and the Emergence of Viral Variants: An Evolutionary Strategies-Inspired Model

The emergence of variants of concern (VOC) has produced challenges in bringing the ongoing COVID-19 pandemic under control, and has created obstacles in the ultimate transition to endemicity;indeed, the omicron variant of SARS-CoV-2, the virus that causes COVID-19, caused a wave of unprecedented levels of infection throughout the globe. Although the available COVID-19 vaccines offer significant protection from infection, hospitalization, and death, challenges in vaccine availability globally have limited the efficacy of mass inoculation in controlling viral spread. The present study utilizes an evolutionary strategies (ES)-inspired model to examine the effect of vaccination upon the emergence of viral variants. The kinetics of the evolution of an idealized RNA virus are modelled in the details of the mutation of an ES population, and the emergence of variants is formulated as an optimization problem. A binary fitness function is optimized such that it achieves a maximum upon the condition that a single viral genome exhibits the requisite number of mutations such that it may be considered a variant of concern. Results demonstrate that vaccination is extremely effective in delaying the emergence of viral variants, and that vaccination rates are highly correlated with delayed variant emergence (R= 0.8399) and requisite viral genetic diversity for consideration as a variant of concern (R=0.8583). Time to emergence of a variant of concern for 0%, 25%, 50%, and 80% vaccination rates of the population are 17.46\pm 1.61 generations, 20.51\pm 2.12 generations, 33.67\pm 5.18 generations, and 226.12\pm 114.41 generations, respectively. It is shown that the delay in emergence of a variant of concern with higher vaccination rates may be attributable to a decrease in the number of infections, thus requiring a higher degree of genetic diversity in the viral genome. © 2022 IEEE.

High mortality and morbidity among vaccinated residents infected with the SARS-CoV-2 Omicron variant during an outbreak in a nursing home in Kyoto City, Japan.

BACKGROUND: Outbreaks of coronavirus disease 2019 (COVID-19) in long-term care facilities are associated with mortality, although vaccination have contributed to improvements. This study reports clinical impacts of a COVID-19 outbreak in a nursing home for elderly individuals in Kyoto City, Japan. METHODS: We performed epidemiologic and molecular investigations of the outbreak and characterized outcomes of the nursing home residents. RESULTS: During the outbreak period, a total of 31 residents (39.2%) and 26 staff members (49.1%) were infected with COVID-19. All residents and staff received two doses of a vaccine approximately 7 months prior. Ten residents with severe hypoxemia could not be transferred to a hospital due to a shortage of beds for COVID-19 patients. Within 90 days of the onset of the outbreak, 8 residents with COVID-19 (25.8%) died. A total of 48.4% of residents with COVID-19 developed 1 or more comorbidities. Viral genome analysis showed that the outbreak was caused by the Omicron BA.1.1.2 variant. CONCLUSIONS: Despite vaccination, high mortality and morbidity were observed in the COVID-19 outbreak due to the Omicron variant. Limiting medical care for residents with COVID-19 in facilities that experience ongoing outbreaks may be needed to reduce the risk of mortality among nursing home residents.

A Deep Learning Approach for Viral DNA Sequence Classification using Genetic Algorithm

DNA sequence classification is one of the major challenges in biological data processing. The identification and classification of novel viral genome sequences drastically help in reducing the dangers of a viral outbreak like COVID-19. The more accurate the classification of these viruses, the faster a vaccine can be produced to counter them. Thus, more accurate methods should be utilized to classify the viral DNA. This research proposes a hybrid deep learning model for efficient viral DNA sequence classification. A genetic algorithm (GA) was utilized for weight optimization with Convolutional Neural Networks (CNN) architecture. Furthermore, Long Short-Term Memory (LSTM) as well as Bidirectional CNN-LSTM model architectures are employed. Encoding methods are needed to transform the DNA into numeric format for the proposed model. Three different encoding methods to represent DNA sequences as input to the proposed model were experimented: k-mer, label encoding, and one hot vector encoding. Furthermore, an efficient oversampling method was applied to overcome the imbalanced dataset issues. The performance of the proposed GA optimized CNN hybrid model using label encoding achieved the highest classification accuracy of 94.88% compared with other encoding methods © 2022, International Journal of Advanced Computer Science and Applications.All Rights Reserved.

Comprehensive Subcellular Localization of Swine Acute Diarrhea Syndrome Coronavirus Proteins.

Bats are reservoirs for diverse coronaviruses, including swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV was first identified in diarrheal piglets in 2017. As a novel alphacoronavirus, SADS-CoV shares ~95% identity with bat alphacoronavirus HKU2. SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. Thus far, no effective antiviral drugs or vaccines are available to treat infections with SADS-CoV. Therefore, knowledge of the protein-coding gene set and a subcellular localization map of SADS-CoV proteins are fundamental first steps in this endeavor. Here, all SADS-CoV genes were cloned separately into Flag-tagged plasmids, and the subcellular localizations of viral proteins, with the exception of nsp11, were detected using confocal microscopy techniques. As a result, nsp1, nsp3-N, nsp4, nsp5, nsp7, nsp8, nsp9, nsp10, nsp14, and nsp15 were localized in the cytoplasm and nuclear spaces, and these viral proteins may perform specific functions in the nucleus. All structural and accessory proteins were mainly localized in the cytoplasm. NS7a and membrane protein M colocalized with the Golgi compartment, and they may regulate the assembly of SADS-CoV virions. Maturation of SADS-CoV may occur in the late endosomes, during which envelope protein E is involved in the assembly and release of the virus. In summary, the present study demonstrates for the first time the location of all the viral proteins of SADS-CoV. These fundamental studies of SADS-CoV will promote studies of basic virology of SADS-CoV and support preventive strategies for animals with infection of SADS-CoV. IMPORTANCE SADS-CoV is the first documented spillover of a bat coronavirus that causes severe diseases in domestic animals. Our study is an in-depth annotation of the newly discovered swine coronavirus SADS-CoV genome and viral protein expression. Systematic subcellular localization of SADS-CoV proteins can have dramatic significance in revealing viral protein biological functions in the subcellular locations. Furthermore, our study promote understanding the fundamental science behind the novel swine coronavirus to pave the way for treatments and cures.

A comprehensive genomic study, mutation screening, phylogenetic and statistical analysis of SARS-CoV-2 and its variant omicron among different countries.

BACKGROUND: With the rapid development of the genomic sequence data for the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants Delta (B.1.617.2) and Omicron (B.1.1.529), it is vital to successfully identify mutations within the genome. OBJECTIVE: The main objective of the study is to investigate the full-length genome mutation analysis of 157 SARS-CoV-2 and its variant Delta and Omicron isolates. This study also provides possible effects at the structural level to understand the role of mutations and new insights into the evolution of COVID-19 and evaluates the differential level analysis in viral genome sequence among different nations. We have also tried to offer a mutation snapshot for these differences that could help in vaccine formulation. This study utilizes a unique and efficient method of targeting the stable genes for the drug discovery approach. METHODS: Complete genome sequence information of SARS-CoV-2, Delta, and Omicron from online resources were used to predict structure domain identification, data mining, and screening; employing different bioinformatics tools. BioEdit software was used to perform their genomic alignments across countries and a phylogenetic tree as per the confidence of 500 bootstrapping values was constructed. Heterozygosity ratios were determined in-silico. A minimum spanning network (MSN) of selected populations was determined by Bruvo's distance role-based framework. RESULTS: Out of all 157 different strains of SARS-CoV-2 and its variants, and their complete genome sequences from different countries, Corona nucleoca and DUF5515 were observed to be the most conserved domains. All genomes obtained changes in comparison to the Wuhan-Hu-1 strain, mainly in the TRS region (CUAAAC or ACGAAC). We discovered 596 mutations in all genes, with the highest number (321) found in ORF1ab (QHD43415.1), or TRS site mutations found only in ORF7a (1) and ORF10 (2). The Omicron variant has 30 mutations in the Spike protein and has a higher alpha-helix shape (23.46%) than the Delta version (22.03%). T478 was also discovered to be a prevalent polymorphism in Delta and Omicron variations, as well as genomic gaps ranging from 45 to 65aa. All 157 sequences contained variations and conformed to Nei's Genetic distance. We discovered heterozygosity (Hs) 0.01, mean anticipated Hs 0.32, the genetic diversity index (GDI) 0.01943989, and GD within population 0.01266951. The Hedrick value was 0.52324978, the GD coefficient was 0.52324978, the average Hs was 0.01371452, and the GD coefficient was 0.52324978. Among other countries, Brazil has the highest standard error (SE) rate (1.398), whereas Japan has the highest ratio of Nei's gene diversity (0.01). CONCLUSIONS: The study's findings will assist in comprehending the shape and kind of complete genome, their streaming genomic sequences, and mutations in various additions of SARS-CoV-2, as well as its different variant strains like Omicron. These results will provide a scientific basis to design the vaccines and understand the genomic study of these viruses.

Application of Continuous Embedding of Viral Genome Sequences and Machine Learning in the Prediction of SARS-CoV-2 Variants

Since the beginning of the novel coronavirus pandemic, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread to 224 countries with over 430 million confirmed cases and more than 5,97 million deaths worldwide. One of the crucial reasons why the spread of the virus was difficult to stop was the viral evolution over time. The emergence of new virus variants is hindering the development of effective drugs and vaccines. Moreover, they contribute e.g. to virus transmissibility or viral immune evasion. This fact has led to increased importance of understanding genomic data related to SARS-CoV-2. In this study, we are proposing sarscov2vec, a new application of continuous vector space representation on novel species of coronaviruses genomes. With its core methodology of genome feature extraction step and being supervised by a Machine Learning model, this tool is designed to distinguish the most common five different SARS-CoV-2 variants: Alpha, Beta, Delta, Gamma and Omicron. In this research we used 367,004 unique genome sequence records from the official virus repositories, where 25,000 sequences were randomly selected and used to train the Natural Language Processing (NLP) algorithm. The next 36,365 samples were processed by a Machine Learning pipeline. Our research results show that the final hiper-tuned classification model achieved 99% of accuracy on the test set. Furthermore, this study demonstrated that the continuous vector space representation of SARS-CoV-2 genomes can be decomposed into 2D vector space and visualized as a method of explaining Machine Learning model decisions. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

A Novel Approach of Antiviral Drugs Targeting Viral Genomes.

Outbreaks of viral diseases, which cause morbidity and mortality in animals and humans, are increasing annually worldwide. Vaccines, antiviral drugs, and antibody therapeutics are the most effective tools for combating viral infection. The ongoing coronavirus disease 2019 pandemic, in particular, raises an urgent need for the development of rapid and broad-spectrum therapeutics. Current antiviral drugs and antiviral antibodies, which are mostly specific at protein levels, have encountered difficulties because the rapid evolution of mutant viral strains resulted in drug resistance. Therefore, degrading viral genomes is considered a novel approach for developing antiviral drugs. The current article highlights all potent candidates that exhibit antiviral activity by digesting viral genomes such as RNases, RNA interference, interferon-stimulated genes 20, and CRISPR/Cas systems. Besides that, we introduce a potential single-chain variable fragment (scFv) that presents antiviral activity against various DNA and RNA viruses due to its unique nucleic acid hydrolyzing characteristic, promoting it as a promising candidate for broad-spectrum antiviral therapeutics.

Transmissibility of SARS-CoV-2 B.1.1.214 and Alpha Variants during 4 COVID-19 Waves, Kyoto, Japan, January 2020-June 2021.

Household transmission is a primary source of SARS-CoV-2 spread. We used COVID-19 epidemiologic investigation data and viral genome analysis data collected in the city of Kyoto, Japan, during January 2020-June 2021 to evaluate the effects of different settings and viral strains on SARS-CoV-2 transmission. Epidemiologic investigations of 5,061 COVID-19 cases found that the most common category for close contact was within households (35.3%); this category also had the highest reverse transcription PCR positivity. The prevalent viral lineage shifted from B.1.1.214 in the third wave to the Alpha variant in the fourth wave. The proportion of secondary cases associated with households also increased from the third to fourth waves (27% vs. 29%). Among 564 contacts from 206 households, Alpha variant was significantly associated with household transmission (odds ratio 1.52, 95% CI 1.06-2.18) compared with B.1.1.214. Public health interventions targeting household contacts and specific variants could help control SARS-CoV-2 transmission.