Betacoronavirus Research Articles

On the End of a Nightmare (COVID-19). The Role of the Immune System

After the Chinese epidemic of Wuhan and the global pandemic that followed, the spread of the coronavirus CoV-SARS-2 has finally come to an end. Already declared the end in the United Kingdom on 19 July 2021, which had primarily started vaccinations on 8 December 2020, aimed in particular at "over" 80 and frail subjects, the whole world has aligned, in particular also taking into account the therapies oral and monoclonal antibodies with a virus that while maintaining its contagiousness has reduced in its virulence. The African continent has stood out for its endemicity linked to zoonoses of the beta coronavirus family. Finally, particular importance is given to the natural infection from COVID-19 and to the immune response with the vaccination exemption due to the risk of thrombi due to genetic mutation and antibody overload.

Suppression of porcine hemagglutinating encephalomyelitis virus replication by resveratrol

BackgroundPorcine hemagglutinating encephalomyelitis virus (PHEV), a member of the genus Betacoronavirus, is the causative agent of neurological disease in pigs. No effective therapeutics are currently available for PHEV infection. Resveratrol has been shown to exert neuroprotective and antiviral effects. Here resveratrol was investigated for its ability to inhibit PHEV replication in nerve cells and central nervous system tissues.MethodsAnti-PHEV effect of resveratrol was evaluated using an in vitro cell-based PHEV infection model and employing a mouse PHEV infection model. The collected cells or tissues were used for quantitative PCR analysis, western blot analysis, or indirect immunofluorescence assay. The supernatants were collected to quantify viral loads by TCID50 assay in vitro. EC50 and CC50 were determined by dose–response experiments, and the ratio (EC50/CC50) was used as a selectivity index (SI) to measure the antiviral versus cytotoxic activity.ResultsOur results showed that resveratrol treatment reduced PHEV titer in a dose-dependent manner, with a 50% inhibition concentration of 6.24 μM. A reduction of > 70% of viral protein expression and mRNA copy number and a 19-fold reduction of virus titer were achieved when infected cells were treated with 10 µM resveratrol in a pre-treatment assay. Quantitative PCR analysis and TCID50 assay results revealed that the addition of 10 μM resveratrol to cells after adsorption of PHEV significantly reduced 56% PHEV mRNA copy number and eightfold virus titer. 10 µM resveratrol treatment reduced 46% PHEV mRNA copy number and fourfold virus titer in virus inactivation assay. Moreover, the in vivo data obtained in this work also demonstrated that resveratrol inhibited PHEV replication, and anti-PHEV activities of resveratrol treatment via intranasal installation displayed better than oral gavage.ConclusionThese results indicated that resveratrol exerted antiviral effects under various drug treatment and virus infection conditions in vitro and holds promise as a treatment for PHEV infection in vivo.

An Immunological Review of SARS-CoV-2 Infection and Vaccine Serology: Innate and Adaptive Responses to mRNA, Adenovirus, Inactivated and Protein Subunit Vaccines.

The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, which is defined by its positive-sense single-stranded RNA (ssRNA) structure. It is in the order Nidovirales, suborder Coronaviridae, genus Betacoronavirus, and sub-genus Sarbecovirus (lineage B), together with two bat-derived strains with a 96% genomic homology with other bat coronaviruses (BatCoVand RaTG13). Thus far, two Alphacoronavirus strains, HCoV-229E and HCoV-NL63, along with five Betacoronaviruses, HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2, have been recognized as human coronaviruses (HCoVs). SARS-CoV-2 has resulted in more than six million deaths worldwide since late 2019. The appearance of this novel virus is defined by its high and variable transmission rate (RT) and coexisting asymptomatic and symptomatic propagation within and across animal populations, which has a longer-lasting impact. Most current therapeutic methods aim to reduce the severity of COVID-19 hospitalization and virus symptoms, preventing the infection from progressing from acute to chronic in vulnerable populations. Now, pharmacological interventions including vaccines and others exist, with research ongoing. The only ethical approach to developing herd immunity is to develop and provide vaccines and therapeutics that can potentially improve on the innate and adaptive system responses at the same time. Therefore, several vaccines have been developed to provide acquired immunity to SARS-CoV-2 induced COVID-19-disease. The initial evaluations of the COVID-19 vaccines began in around 2020, followed by clinical trials carried out during the pandemic with ongoing population adverse effect monitoring by respective regulatory agencies. Therefore, durability and immunity provided by current vaccines requires further characterization with more extensive available data, as is presented in this paper. When utilized globally, these vaccines may create an unidentified pattern of antibody responses or memory B and T cell responses that need to be further researched, some of which can now be compared within laboratory and population studies here. Several COVID-19 vaccine immunogens have been presented in clinical trials to assess their safety and efficacy, inducing cellular antibody production through cellular B and T cell interactions that protect against infection. This response is defined by virus-specific antibodies (anti-N or anti-S antibodies), with B and T cell characterization undergoing extensive research. In this article, we review four types of contemporary COVID-19 vaccines, comparing their antibody profiles and cellular aspects involved in coronavirus immunology across several population studies.

SARS-CoV-2: An Updated Review Highlighting Its Evolution and Treatments.

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

Potential therapeutic value of necroptosis inhibitor for the treatment of COVID-19

The coronavirus disease 2019 (COVID-19), caused by a novel virus of the beta-coronavirus genus (SARS-CoV-2), has spread rapidly, posing a significant threat to global health. There are currently no drugs available for effective treatment. Severe cases of COVID-19 are associated with hyperinflammation, also known as cytokine storm syndrome. The reduce inflammation are considered promising treatments for COVID-19. Necroptosis is a type of programmed necrosis involved in immune response to viral infection, and severe inflammatory injury. Inhibition of necroptosis is pivotal in preventing associated inflammatory responses. The expression of key regulators of the necroptosis pathway is generally up-regulated in COVID-19, indicating that the necroptosis pathway is activated. Thus, necroptosis inhibitors are expected to be novel therapeutic candidates for the treatment of COVID-19.Better knowledge of the necroptosis pathway mechanism is urgently required to solve the remaining mysteries surrounding the role of necroptosis in COVID-19. In this review, we briefly introduce the pathogenesis of necroptosis, the relationship between necroptosis, cytokine storm, and COVID-19 also summarizes the progress of inhibitors of necroptosis. This research provides a timely and necessary suggest of the development of necroptosis inhibitors to treat COVID-19 and clinical transformation of inhibitors of necroptosis.

A Phase 1a/1b Clinical Trial Design to Assess Safety, Acceptability, Pharmacokinetics and Tolerability of Intranasal Q-Griffithsin for COVID-19 Prophylaxis

Background: The COVID-19 pandemic remains an ongoing threat to global public health. Q-Griffithsin (Q-GRFT) is a lectin that has demonstrated potent broad-spectrum inhibitory activity in preclinical studies in models of Nipah virus and the beta coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2.

MSClustering: A Cytoscape Tool for Multi-Level Clustering of Biological Networks.

MSClustering is an efficient software package for visualizing and analyzing complex networks in Cytoscape. Based on the distance matrix of a network that it takes as input, MSClustering automatically displays the minimum span clustering (MSC) of the network at various characteristic levels. To produce a view of the overall network structure, the app then organizes the multi-level results into an MSC tree. Here, we demonstrate the package's phylogenetic applications in studying the evolutionary relationships of complex systems, including 63 beta coronaviruses and 197 GPCRs. The validity of MSClustering for large systems has been verified by its clustering of 3481 enzymes. Through an experimental comparison, we show that MSClustering outperforms five different state-of-the-art methods in the efficiency and reliability of their clustering.

Intra-laboratory validated “TigraTest® SARS-CoV-2” — test assessing release of interferon gamma in vitro to identify peripheral blood T-lymphocytes specifically responding against SARS-CoV-2 virus antigens

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), also known as 2019-nCoV (2019-Novel Coronavirus) is a strain of coronavirus from the genus Betacoronavirus, discovered in China at the end of 2019 in patients with pneumonia. Coronavirus infection COVID-19 (COrona VIrus Disease 2019) caused by coronavirus 2019 (COVID-19) has spread around the world at a very fast pace, with death toll exceeding more than 5.2 million people worldwide. Limited success in developing new drugs as well as use of existing drugs for the treatment of COVID-19 resulted in situation when the main prevention measures for a long time were based on testing and isolation of sick subjects, which started to reverse due to vaccination. Monitoring the formation of humoral and T-cell population immunity against the SARS-CoV-2 virus during the COVID-19 pandemic is a necessary element for epidemiological surveillance. ELISA-based methods are widely used to assess humoral immunity, and various test systems including ELISPOT (Enzyme-Linked ImmunoSpot) are used to analyze cellular immunity. The ELISPOT assay is a highly sensitive and specific method for quantifying individual cytokine-secreting T cells after being stimulated with a specific antigen. TigraTest SARS-CoV-2 Test assessing release of interferon gamma in vitro to detect peripheral blood T-lymphocytes that specifically respond to the SARS-CoV-2 virus antigens manufactured by GENERIUM JSC, is created on the ELISPOT platform. This study describes the procedure for laboratory validation of this test system to analyze the following parameters: specificity of antibody pair, effect of interfering substances, sensitivity and specificity, precision, stability of blood samples till isolation of target cells. The developed test system showed high diagnostic sensitivity and specificity. The specificity of TigraTest SARS-CoV-2 was 100%, the sensitivity for subjects immunized with the Gam-COVID-Vac vaccine (Sputnik V) was 91.67%, and the sensitivity in convalescent COVID-19 patients was 95.45%. At the same time, the data variability both during within and between series comparison did not exceed 25%, whereas 24-hour storage of peripheral blood samples at (1825)С after blood collection followed by isolation of target cells did not affect the test results.

Could platelet indices have diagnostic properties in children with COVID-19?

Viral infections are often accompanied by reactive thrombocytosis, that is, increased activity of platelets, which is especially common in infants and children. This study aimed to test the diagnostic properties of platelet indices, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW), in children with beta corona virus 2 (SARS-CoV-2) infection. The study included 232 patients below the age of 18 admitted to the coronavirus disease (COVID-19) isolation wards at the Institute for Child and Youth Health Care of Vojvodina. PCT, MPV and PDW values on the day of admission were recorded. In total, 245 controls were selected from those treated for SARS-CoV-2 negative respiratory infections. Descriptive and inferential statistical analyses were performed. MPV and PDW were found important as independent predictors for COVID-19 in children. Furthermore, the joint effect of MPV and PDW for predicting COVID-19 was confirmed. The parameters showed better sensitivity than specificity. Our study showed that PCT is not clinically significant, while MPV and PDW have diagnostic value in predicting COVID-19 in children. In perspective, these parameters could be implemented in the various learning algorithms in order to achieve earlier diagnosis and treatment.

Study of Clinical Profile & Outcome in Elderly Patients with COVID-19

Introduction: Novel beta coronavirus (SARS-CoV-2) has caused widespread transmission of coronavirus illness (COVID-19) in India from March 2020. In comparison to younger adults, older people and those with numerous co-morbidities are known to be more severely affected by seasonal flu and to have a higher mortality rate. The mortality rate increases significantly in the age groups over 60 years old with SARS-CoV-2 infection. With this objective present study was undertaken to study clinical profile and outcome in elderly COVID 19 patients
 Materials and Methods: Data of 100 elderly patients aged 60 years and older with COVID-19 were obtained from hospital record section. It consisted of clinical characteristics, respiratory manifestations, laboratory parameters and radiological findings. COVID-19 confirmation was based on reverse transcription polymerase chain reaction (RT-PCR). 100 patients were divided into two groups based on outcome as Group A (Survivors) and Group B (Non-Survivors). They included 66 males and 34 females.
 Observation and Results: Respiratory rate more than 30 was mainly present in group B patients (19%) compared to group A. In majority patients i.e. 79 (79%) SpO2 was between 80 to 95 range and majority i.e. 35 (35%) given Oxygen via nasal prongs. Haemoglobin <12 and Leucocytes ≤ 11000 was found in maximum patients. CRP, D dimer and random blood sugar showed statistically significant difference between two groups (P<0.0001). Ground glass opacities was main pattern found in 46 (46%), Bilateral Consolidation found in 41 (41%) and Unilateral Consolidation in 13 (13%). Results showed no statistically significant difference amongst two groups (P=0.725)
 Discussion: A progressive and relatively linear increase in nasal cavity volume with increasing age along with an age-dependent decrease of nasal resistance are possible determinants for a higher prevalence of COVID in the elderly population
 Conclusion: An individualized approach should be offered to older adults targeting the beneficial and negative effects of therapeutic approach

Antiviral effect of lysosomotropic disaccharide trehalose on porcine hemagglutinating encephalomyelitis virus, a highly neurotropic betacoronavirus

Many members of the genus Betacoronavirus are neurotropic viruses that frequently cause serious harm to humans or animals, including highly neurotropic porcine hemagglutinating encephalomyelitis virus (PHEV). Nevertheless, very few approved treatments exist to combat these viruses. Lysosomotropic trehalose, a widely used, nontoxic, natural disaccharide that can traverse the blood-brain barrier, has been proposed as a potential antiviral agent for use in prevention or treatment of betacoronavirus-associated infections. The purpose of this study was to determine if trehalose could inhibit PHEV infection of cells of a mouse central nervous system-derived neuroblastoma cell line in vitro or brain cells in vivo. Our results demonstrated that treatment of PHEV-infected mouse neuroblastoma cells and mice with trehalose reduced viral replication and that these trehalose antiviral effects were dependent on expression of lysosomal protein progranulin. Collectively, these results indicated that trehalose holds promise as a new antiviral agent for use in controlling neurotropic betacoronavirus infections.

Identification of Doxorubicin as Repurposing Inhibitory Drug for MERS-CoV PLpro.

Middle East respiratory syndrome coronavirus (MERS-CoV), belonging to the betacoronavirus genus can cause severe respiratory illnesses, accompanied by pneumonia, multiorgan failure, and ultimately death. CoVs have the ability to transgress species barriers and spread swiftly into new host species, with human-to-human transmission causing epidemic diseases. Despite the severe public health threat of MERS-CoV, there are currently no vaccines or drugs available for its treatment. MERS-CoV papain-like protease (PLpro) is a key enzyme that plays an important role in its replication. In the present study, we evaluated the inhibitory activities of doxorubicin (DOX) against the recombinant MERS-CoV PLpro by employing protease inhibition assays. Hydrolysis of fluorogenic peptide from the Z-RLRGG-AMC-peptide bond in the presence of DOX showed an IC50 value of 1.67 μM at 30 min. Subsequently, we confirmed the interaction between DOX and MERS-CoV PLpro by thermal shift assay (TSA), and DOX increased ΔTm by ~20 °C, clearly indicating a coherent interaction between the MERS-CoV PL protease and DOX. The binding site of DOX on MERS-CoV PLpro was assessed using docking techniques and molecular dynamic (MD) simulations. DOX bound to the thumb region of the catalytic domain of the MERS-CoV PLpro. MD simulation results showed flexible BL2 loops, as well as other potential residues, such as R231, R233, and G276 of MERS-CoV PLpro. Development of drug repurposing is a remarkable opportunity to quickly examine the efficacy of different aspects of treating various diseases. Protease inhibitors have been found to be effective against MERS-CoV to date, and numerous candidates are currently undergoing clinical trials to prove this. Our effort follows a in similar direction.

A study of viral pathogens in bat species in the Iberian Peninsula: identification of new coronavirus genetic variants

ABSTRACT Bats have long been associated with multiple pathogens, including viruses affecting humans such as henipaviruses, filoviruses, bunyaviruses and coronaviruses. The alpha and beta coronaviruses genera can infect most mammalian species. Among them, betacoronavirus SARS-CoV, MERS-CoV and SARS-CoV-2, which have caused the three major pandemics in the last two decades, have been proposed to originate in bats. In this study, 194 oral swabs from 22 bats species sampled in 19 locations of the Iberian Peninsula were analysed and characterized by three different PCR tests (coronavirus generic real-time RT-PCR, multiplex conventional PCR, and SARS-CoV-2 specific real-time RT-PCR) to detect bat coronaviruses. Screening with coronavirus generic PCR showed 102 positives out of 194 oral swabs analysed. Then, metabarcoding with multiplex PCR amplified 15 positive samples. Most of the coronaviruses detected in this study belong to alphacoronavirus (α-CoV) genus, with multiple alphacoronaviruses identified by up to five different genetic variants coexisting in the same bat. One of the positive samples identified in a Miniopterus schreibersii bat positive for the generic coronavirus PCR and the specific SARS-CoV-2 PCR was classified as betacoronavirus (β-CoV) through phylogenetic analysis. These results support the rapid evolution of coronaviruses to generate new genomic potentially pathogenic variants likely through co-infection and recombination.

An Updated Review on Complicated Mechanisms of COVID-19 Pathogenesis and Therapy: Direct Viral Damage, Renin-angiotensin System Dysregulation, Immune System Derangements, and Endothelial Dysfunction.

SARS-CoV-2 was reported as the cause of coronavirus disease 2019 (COVID-19) in late December 2019. According to sequencing and phylogenetic studies, the new virus belongs to Coronaviridae family and Betacoronavirus genus. Genomic sequence analysis has shown SARS-CoV-2 to be similar to SARS. SARS-CoV-2 is more infectious, and the high level of COVID-19 community transmission has led to a growing pandemic. Although infections in most patients with COVID-19 are moderate or mild, 20% of the patients develop a severe or critical form of the disease. COVID-19 may affect a wide range of organs and tissues, including the respiratory system, digestive system, nervous system, and skin. Patients with COVID-19 have been confirmed to have renal, cardiovascular, gastrointestinal, and nervous system problems in addition to pulmonary involvement. The pathogenesis of SARS-CoV-2 is being investigated, but it is possible that the organ damage might in part be caused by direct viral damage (detection of inclusion bodies in tissues, such as the kidneys), dysregulation of the immune system, renin-angiotensin system, bradykinin pathway, and coagulation, as well as host genetic factors and their polymorphisms, which may affect the disease severity. In this review, an update on the possible pathogenesis pathways of COVID-19 has been provided. It is hoped that the best care strategy will be developed for patients with COVID-19 by identifying its pathogenesis pathways.

Emergence and spreading of the largest SARS-CoV-2 deletion in the Delta AY.20 lineage from Uruguay

The genetic variability of SARS-CoV-2 (genus Betacoronavirus, family Coronaviridae) has been scrutinized since its first detection in December 2019. Although the role of structural variants, particularly deletions, in virus evolution is little explored, these genome changes are extremely frequent. They are associated with relevant processes, including immune escape and attenuation. Deletions commonly occur in accessory ORFs and might even lead to the complete loss of one or more ORFs. This scenario poses an interesting question about the origin and spreading of extreme structural rearrangements that persist without compromising virus viability. Here, we analyze the genome of SARS-CoV-2 in late 2021 in Uruguay and identify a Delta lineage (AY.20) that experienced a large deletion (872 nucleotides according to the reference Wuhan strain) that removes the 7a, 7b, and 8 ORFs. Deleted viruses coexist with wild-type (without deletion) AY.20 and AY.43 strains. The Uruguayan deletion is like those identified in Delta strains from Poland and Japan but occurs in a different Delta clade. Besides providing proof of the circulation of this large deletion in America, we infer that the 872-deletion arises by the consecutive occurrence of a 6-nucleotide deletion, characteristic of delta strains, and an 866-nucleotide deletion that arose independently in the AY.20 Uruguayan lineage. The largest deletion occurs adjacent to transcription regulatory sequences needed to synthesize the nested set of subgenomic mRNAs that serve as templates for transcription. Our findings support the role of transcription sequences as a hotspot for copy-choice recombination and highlight the remarkable dynamic of SARS-CoV-2 genomes.

Attitudes and Intentions of Health Personnel towards Covid-19 Vaccination in Kaziba Health Zone

Introduction: SARS-CoV-2 is a virus of the coronavidae family and of the beta coronavirus group, such as those responsible for SARS and MERS. This Covid-19 is more contagious than SARS and MERS but with a lower death rate. Covid-19 vaccine is a pharmaceutical tool to control the transmission of Covid-19 among the health personnel and the general population. The acceptance of Covid-19 vaccination remains reluctant among the health personnel. The purposes of this study are to determine the intentions and attitudes of health personnel vis-à-vis to Covid-19 vaccination and, to determine the reasons for accepting and refusing Covid-19 vaccination among health personnel in Kaziba Health Zone from 15 to 28 July 2021. Material and methods: our study was descriptive retrospective cross-sectional study. A random sampling method was carried out to collect the data through survey questionnaire with 102 health personnel. The data was analyzed with SPSS and Chi-square test was carried out. Results: the intentions and attitudes of the health personnel vis-à-vis to Covid-19 vaccination was (31.4%), and the participants who declared the mandatory Covid-19 vaccination was 31.4%. The health personnel who accepted the covid-19 vaccine were 21.6%, however, those who refused was 45.1%. Conclusion: health personnel do not have acceptable intentions and attitudes towards Covid-19 vaccination. Only nurses and midwives, physicians and healthcare assistance staff were agreeable to Covid-19 vaccination to control the pandemic. Lack of information was the main refusal reason for Covid-19 vaccination. The health personnel were not willingly too mandatory Covid-19 vaccination. Keywords: Attitudes, Covid-19, Health personnel, Intentions, Kaziba, SARS-CoV-2, Vaccination.

A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice.

Gamma-aminobutyric acid (GABA) and GABA-receptors (GABA-Rs) form a major neurotransmitter system in the brain. GABA-Rs are also expressed by 1) cells of the innate and adaptive immune system and act to inhibit their inflammatory activities, and 2) lung epithelial cells and GABA-R agonists/potentiators have been observed to limit acute lung injuries. These biological properties suggest that GABA-R agonists may have potential for treating COVID-19. We previously reported that GABA-R agonist treatments protected mice from severe disease induced by infection with a lethal mouse coronavirus (MHV-1). Because MHV-1 targets different cellular receptors and is biologically distinct from SARS-CoV-2, we sought to test GABA therapy in K18-hACE2 mice which develop severe pneumonitis with high lethality following SARS-CoV-2 infection. We observed that GABA treatment initiated immediately after SARS-CoV-2 infection, or 2 days later near the peak of lung viral load, reduced pneumonitis severity and death rates in K18-hACE2 mice. GABA-treated mice had reduced lung viral loads and displayed shifts in their serum cytokine/chemokine levels that are associated with better outcomes in COVID-19 patients. Thus, GABA-R activation had multiple effects that are also desirable for the treatment of COVID-19. The protective effects of GABA against two very different beta coronaviruses (SARS-CoV-2 and MHV-1) suggest that it may provide a generalizable off-the-shelf therapy to help treat diseases induced by new SARS-CoV-2 variants and novel coronaviruses that evade immune responses and antiviral medications. GABA is inexpensive, safe for human use, and stable at room temperature, making it an attractive candidate for testing in clinical trials. We also discuss the potential of GABA-R agonists for limiting COVID-19-associated neuroinflammation.

Insight into genomic organization of pathogenic coronaviruses, SARS-CoV-2: Implication for emergence of new variants, laboratory diagnosis and treatment options.

SARS-CoV-2 is a novel zoonotic positive-sense RNA virus (ssRNA+) belonging to the genus beta coronaviruses (CoVs) in the Coronaviridae family. It is the causative agent for the outbreak of the disease, COVID-19. It is the third CoV causing pneumonia around the world in the past 2decades. To date, it has caused significant deaths worldwide. Notably, the emergence of new genetic variants conferring efficient transmission and immune evasion remained a challenge, despite the reduction in the number of death cases, owing to effective vaccination regimen (boosting) and safety protocols. Thus, information harnessed from SARS-CoV-2 genomic organization is indispensable for seeking laboratory diagnosis and treatment options. Here in, we review previously circulating variants of SARS-CoV-2 designated variant of concern (VOC) including the Alpha (United Kingdom), Beta (South Africa), Gamma (Brazil), Delta (India), and recently circulating VOC, Omicron (South Africa) and its divergent subvariants (BA.1, BA.2, BA.3, BA.2.12.1, BA.4 and BA.5) with BA.5 currently becoming dominant and prolonging the COVID pandemic. In addition, we address the role of computational models for mutagenesis analysis which can predict important residues that contribute to transmissibility, virulence, immune evasion, and molecular detections of SARS-CoV-2. Concomitantly, the importance of harnessing the immunobiology of SARS-CoV-2 and host interaction for therapeutic purpose; and use of an in slilico based biocomputational approaches to achieve this purpose via predicting novel therapeutic agents targeting PRR such as toll like receptor, design of universal vaccine and chimeric antibodies tailored to the emergent variant have been highlighted.

Impact of COVID-19 Nonpharmaceutical Interventions on the Extent of Norovirus Contamination in Oyster Production Areas in Ireland during Winter 2020 to 2021

A significant decrease in norovirus prevalence and concentration was observed in oyster production areas in Ireland during winter 2020 to 2021. Oyster production areas impacted by human wastewater discharges that had been undergoing norovirus surveillance since 2018 were investigated. Samples collected in the winter seasons of 2018 to 2019 and 2019 to 2020, prior to when the COVID-19 pandemic interventions were applied, showed a prevalence of 94.3 and 96.6%, respectively, and geometric mean concentrations of 533 and 323 genome copies per g, respectively. These values decreased significantly during the winter of 2020 to 2021 (prevalence of 63.2% and geometric concentration of below the limit of quantification), coinciding with the control measures to mitigate the transmission of severe acute respiratory syndrome coronavirus 2 of the genus Betacoronavirus. Divergence between norovirus GI and GII prevalence and concentrations was observed over the 3-year monitoring period. Norovirus GII was the dominant genogroup detected in winter 2020 to 2021, with over half of samples positive, although concentrations detected were significantly lower than prepandemic winters, with a geometric mean concentration of below the limit of quantification.

Targeting Citrate Carrier (CIC) in Inflammatory Macrophages as a Novel Metabolic Approach in COVID-19 Patients: A Perspective.

Coronavirus disease-19 (COVID-19) can be a fatal disease and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). SARS-CoV2 is an enveloped virus that belongs to the Beta coronavirus subfamily. After entering into the target cells, this virus replicates rapidly and leads to cellular damage and uncontrolled pulmonary inflammation. Huge amounts of inflammatory cytokines and chemokines are produced by infected lung cells and are associated with monocyte recruitment and accumulation of inflammatory macrophages at the site of infection. Mitochondrial citrate carrier (CIC) expression increases in these macrophages, which results in elevated levels of cytosolic citrate and the production of inflammatory mediators. In this perspective article, we discuss the role of mitochondrial CIC in the metabolism of inflammatory macrophages and we propose that inhibition of this carrier might be a novel therapeutic approach for COVID-19 patients.