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  1. Fulltext Development of virus-like particles-based vaccines against coronaviruses
    Yong CY, Liew WPP, Ong HK, Poh CL
    Biotechnol Prog, 2022 Nov;38(6):e3292.
    PMID: 35932092 DOI: 10.1002/btpr.3292
    Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the most impactful coronaviruses in human history, especially the latter, which brings revolutionary changes to human vaccinology. Due to its high infectivity, the virus spreads rapidly throughout the world and was declared a pandemic in March 2020. A vaccine would normally take more than 10 years to be developed. As such, there is no vaccine available for SARS-CoV and MERS-CoV. Currently, 10 vaccines have been approved for emergency use by World Health Organization (WHO) against SARS-CoV-2. Virus-like particle (VLP)s are nanoparticles resembling the native virus but devoid of the viral genome. Due to their self-adjuvanting properties, VLPs have been explored extensively for vaccine development. However, none of the approved vaccines against SARS-CoV-2 was based on VLP and only 4% of the vaccine candidates in clinical trials were based on VLPs. In the current review, we focused on discussing the major advances in the development of VLP-based vaccine candidates against the SARS-CoV, MERS-CoV, and SARS-CoV-2, including those in clinical and pre-clinical studies, to give a comprehensive overview of the VLP-based vaccines against the coronaviruses.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus*
  2. Fulltext Multiyear prospective cohort study to evaluate the risk potential of MERS-CoV infection among Malaysian Hajj pilgrims (MERCURIAL): a study protocol
    Johari J, Hontz RD, Pike BL, Husain T, Chong CK, Rusli N, et al.
    BMJ Open, 2021 08 26;11(8):e050901.
    PMID: 34446498 DOI: 10.1136/bmjopen-2021-050901
    INTRODUCTION: Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by the MERS-CoV. MERS was first reported in the Kingdom of Saudi Arabia in 2012. Every year, the Hajj pilgrimage to Mecca attracts more than two million pilgrims from 184 countries, making it one of the largest annual religious mass gatherings (MGs) worldwide. MGs in confined areas with a high number of pilgrims' movements worldwide continues to elicit significant global public health concerns. MERCURIAL was designed by adopting a seroconversion surveillance approach to provide multiyear evidence of MG-associated MERS-CoV seroconversion among the Malaysian Hajj pilgrims.

    METHODS AND ANALYSIS: MERCURIAL is an ongoing multiyear prospective cohort study. Every year, for the next 5 years, a cohort of 1000 Hajj pilgrims was enrolled beginning in the 2016 Hajj pilgrimage season. Pre-Hajj and post-Hajj serum samples were obtained and serologically analysed for evidence of MERS-CoV seroconversion. Sociodemographic data, underlying medical conditions, symptoms experienced during Hajj pilgrimage, and exposure to camel and untreated camel products were recorded using structured pre-Hajj and post-Hajj questionnaires. The possible risk factors associated with the seroconversion data were analysed using univariate and multivariate logistic regression. The primary outcome of this study is to better enhance our understanding of the potential threat of MERS-CoV spreading through MG beyond the Middle East.

    ETHICS AND DISSEMINATION: This study has obtained ethical approval from the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia. Results from the study will be submitted for publication in peer-reviewed journals and presented in conferences and scientific meetings.

    TRIAL REGISTRATION NUMBER: NMRR-15-1640-25391.

    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus*
  3. Fulltext Current diagnostic approaches to detect two important betacoronaviruses: Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
    Chong ZX, Liew WPP, Ong HK, Yong CY, Shit CS, Ho WY, et al.
    Pathol Res Pract, 2021 Sep;225:153565.
    PMID: 34333398 DOI: 10.1016/j.prp.2021.153565
    Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are two common betacoronaviruses, which are still causing transmission among the human population worldwide. The major difference between the two coronaviruses is that MERS-CoV is now causing sporadic transmission worldwide, whereas SARS-CoV-2 is causing a pandemic outbreak globally. Currently, different guidelines and reports have highlighted several diagnostic methods and approaches which could be used to screen and confirm MERS-CoV and SARS-CoV-2 infections. These methods include clinical evaluation, laboratory diagnosis (nucleic acid-based test, protein-based test, or viral culture), and radiological diagnosis. With the presence of these different diagnostic approaches, it could cause a dilemma to the clinicians and diagnostic laboratories in selecting the best diagnostic strategies to confirm MERS-CoV and SARS-CoV-2 infections. Therefore, this review aims to provide an up-to-date comparison of the advantages and limitations of different diagnostic approaches in detecting MERS-CoV and SARS-CoV-2 infections. This review could provide insights for clinicians and scientists in detecting MERS-CoV and SARS-CoV-2 infections to help combat the transmission of these coronaviruses.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/pathogenicity*
  4. Fulltext SARS coronavirus outbreaks past and present-a comparative analysis of SARS-CoV-2 and its predecessors
    Low ZY, Yip AJW, Sharma A, Lal SK
    Virus Genes, 2021 Aug;57(4):307-317.
    PMID: 34061288 DOI: 10.1007/s11262-021-01846-9
    The Coronavirus Disease 2019 (COVID-19), a pneumonic disease caused by the SARS Coronavirus 2 (SARS-CoV-2), is the 7th Coronavirus to have successfully infected and caused an outbreak in humans. Genome comparisons have shown that previous isolates, the SARS-related coronavirus (SARSr-CoV), including the SARS-CoV are closely related, yet different in disease manifestation. Several explanations were suggested for the undetermined origin of SARS-CoV-2, in particular, bats, avian and Malayan pangolins as reservoir hosts, owing to the high genetic similarity. The general morphology and structure of all these viral isolates overlap with analogous disease symptoms such as fever, dry cough, fatigue, dyspnoea and headache, very similar to the current SARS-CoV-2. Chest CT scans for SARS-CoV-2, SARS-CoV and MERS-CoV reveal pulmonary lesions, bilateral ground-glass opacities, and segmental consolidation in the lungs, a common pathological trait. With greatly overlapping similarities among the previous coronavirus, the SARS-CoV, it becomes interesting to observe marked differences in disease severity of the SARS-CoV-2 thereby imparting it the ability to rapidly transmit, exhibit greater stability, bypass innate host defences, and increasingly adapt to their new host thereby resulting in the current pandemic. The most recent B.1.1.7, B.1.351 and P.1 variants of SARS-CoV-2, highlight the fact that changes in amino acids in the Spike protein can contribute to enhanced infection and transmission efficiency. This review covers a comparative analysis of previous coronavirus outbreaks and highlights the differences and similarities among different coronaviruses, including the most recent isolates that have evolved to become easily transmissible with higher replication efficiency in humans.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/genetics
  5. Fulltext Guidelines on Middle East Respiratory Syndrome (MERS) Management In Malaysia
    Citation: Guidelines on Middle East Respiratory Syndrome (MERS) Management In Malaysia. Putrajaya: Ministry of Health, Malaysia; 2015

    Keywords: CPG
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
  6. Fulltext Comprehensive Structural and Molecular Comparison of Spike Proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and Their Interactions with ACE2
    Hatmal MM, Alshaer W, Al-Hatamleh MAI, Hatmal M, Smadi O, Taha MO, et al.
    Cells, 2020 Dec 08;9(12).
    PMID: 33302501 DOI: 10.3390/cells9122638
    The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has recently emerged in China and caused a disease called coronavirus disease 2019 (COVID-19). The virus quickly spread around the world, causing a sustained global outbreak. Although SARS-CoV-2, and other coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV) are highly similar genetically and at the protein production level, there are significant differences between them. Research has shown that the structural spike (S) protein plays an important role in the evolution and transmission of SARS-CoV-2. So far, studies have shown that various genes encoding primarily for elements of S protein undergo frequent mutation. We have performed an in-depth review of the literature covering the structural and mutational aspects of S protein in the context of SARS-CoV-2, and compared them with those of SARS-CoV and MERS-CoV. Our analytical approach consisted in an initial genome and transcriptome analysis, followed by primary, secondary and tertiary protein structure analysis. Additionally, we investigated the potential effects of these differences on the S protein binding and interactions to angiotensin-converting enzyme 2 (ACE2), and we established, after extensive analysis of previous research articles, that SARS-CoV-2 and SARS-CoV use different ends/regions in S protein receptor-binding motif (RBM) and different types of interactions for their chief binding with ACE2. These differences may have significant implications on pathogenesis, entry and ability to infect intermediate hosts for these coronaviruses. This review comprehensively addresses in detail the variations in S protein, its receptor-binding characteristics and detailed structural interactions, the process of cleavage involved in priming, as well as other differences between coronaviruses.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/genetics; Middle East Respiratory Syndrome Coronavirus/metabolism*
  7. Fulltext Comparative Study between Covid-19, SARS and MERS
    Sohayla M. Attalla, Kavitha Ashok Kumar, Sakinah Ruhi, Saw Aung, Fazna Saleem, Hassan O. Ads, et al.
    Journal of Optometry, Eye and Health Research, 2020;2(1):19-27.
    MyJurnal
    Coronaviruses were discovered in the mid-1960s then at 2002 in Foshan, China a new virus discovered to cause a Severe Acute Respiratory Syndrome (SARS-CoV) then at 2012 another strain was identified in Saudi Arabia causing the Middle East Respiratory Syndrome (MERS). In December 2019 in Wuhan, Hubei, SARS-CoV-2 (COVID-19) emerged to spread as pandemic. Being a series of the same family, the current research aimed to compare the characteristics of COVID-19 in relation to SARS and MERS regarding the origin and genomic structure, mode of transmission, distribution of cases along the world countries, infectivity and mortality rates together with the clinical presentation, diagnosis and treatment.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
  8. Fulltext A mini-review on the effects of COVID-19 on younger individuals
    Manivannan M, Jogalekar MP, Kavitha MS, Maran BAV, Gangadaran P
    Exp Biol Med (Maywood), 2021 02;246(3):293-297.
    PMID: 33210552 DOI: 10.1177/1535370220975118
    Coronavirus disease 2019 (COVID-19) pandemic has uprooted our lives like never before since its onset in the late December 2019. The world has seen mounting infections and deaths over the past few months despite the unprecedented measures countries are implementing, such as lockdowns, social distancing, mask-wearing, and banning gatherings in large groups. Interestingly, young individuals seem less likely to be impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. While the rate of transmission, symptom presentation, and fatality is lower in children than people from other age groups, they have been disproportionately affected by strict lockdown measures needed to curb viral spread. In this review, we describe the association between patient age and COVID-19, epidemiology of SARS-CoV-2 infection in children, psychological effects associated with lockdowns and school closures, and possible mechanisms underlying lower transmission rate of COVID-19 in children.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
  9. Fulltext Middle East Respiratory Syndrome (MERS) Virus-Pathophysiological Axis and the Current Treatment Strategies
    Alnuqaydan AM, Almutary AG, Sukamaran A, Yang BTW, Lee XT, Lim WX, et al.
    AAPS PharmSciTech, 2021 Jun 08;22(5):173.
    PMID: 34105037 DOI: 10.1208/s12249-021-02062-2
    Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/drug effects; Middle East Respiratory Syndrome Coronavirus/immunology*; Middle East Respiratory Syndrome Coronavirus/isolation & purification
  10. Fulltext Controversies on the Use of Ultraviolet Rays for Disinfection During the COVID-19 Pandemic
    Chew CC, Rajan P
    Malays J Med Sci, 2021 Feb;28(1):117-119.
    PMID: 33679228 DOI: 10.21315/mjms2021.28.1.15
    During the coronavirus disease 2019 (COVID-19) pandemic, the use of ultraviolet (UV) rays to disinfect skin areas, clothes and other objects at the entry/exit points of public spaces has been widely discussed by stakeholders. While ultraviolet germicidal irradiation (UVGI) has been shown to effectively inactivate coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV)-1 and Middle East respiratory syndrome coronavirus (MERS-CoV), no specific evidence proves that it effectively inactivates the new SARS-CoV-2 virus that causes COVID-19. Because UV rays damage human tissue, UVGI should be used with caution and not directly on human skin. Various guidelines recommend that UVGI should not be used as a sole agent for disinfecting surfaces or objects but as an adjunct to the latest standard disinfecting procedures.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
  11. Fulltext MERS-CoV seroconversion amongst Malaysian Hajj pilgrims returning from the Middle East, 2016-2018: results from the MERCURIAL multiyear prospective cohort study
    Johari J, Hontz RD, Pike BL, Husain T, Rusli N, Mohd-Zain R, et al.
    Emerg Microbes Infect, 2023 Dec;12(1):2208678.
    PMID: 37101375 DOI: 10.1080/22221751.2023.2208678
    Prospective cohort study to investigate the potential exposure to the Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) following Hajj pilgrims is still very limited. Here, we report the antibody seroconversion study results obtained from successive three years cohort studies (2016-2018) involving the Malaysian Hajj pilgrims returning from the Middle East. A cohort study of Hajj pilgrims from Malaysia enrolled 2,863 participants from 2016-2018, all of whom consented to provide paired blood samples for both pre- and post-Hajj travel to the Middle East. ELISAs and micro-neutralization assays were performed to detect the presence of MERS-CoV IgG antibodies. Sociodemographic data, symptoms experienced during Hajj, and history of exposure to camels or camel products were recorded using structured pre- and post-Hajj questionnaires. A 4-fold increase in anti-MERS-CoV IgG between paired pre-Hajj and post-Hajj serum samples in twelve participants was observed. None of the twelve ELISA-positive sera had detectable levels of virus-neutralizing antibodies. All reportedly had mild symptoms of respiratory symptoms at a certain point during the pilgrimage, implying mild or asymptomatic infections. No association between post-Hajj serum positivity and a history of exposure to camels or camel products was obtained. Findings from the study suggest that serologic conversion to MERS-CoV occurred in at least 0.6% of the Hajj pilgrims returning from the Middle East. Since all the seroconvertants had mild to no symptoms during the sampling period, it highlights the likelihood of occurrence of only low infectivity spillover infections among the Hajj pilgrims.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus*
  12. Impact of COVID-19 in public health: Prevalence and preventive approaches
    Subramaniyan V, Chakravarthi S, Seng WY, Kayarohanam S, Fuloria NK, Fuloria S
    Pak J Pharm Sci, 2020 Jul;33(4):1739-1745.
    PMID: 33583811
    The outbreak of CoVID-19 infection rapidly increases worldwide. Most of the continents affecting from CoVID-19 and still widening its burden disease (Jones DS, 2020; Lai et al., 2020). Along with its fatality rates, CoVID-19 has caused physiological disturbances in the society and termed as "coronophobia". CoVID-19 with renal failure, severe pneumonia and respiratory syndrome patients have been reported to increase the severity of disease conditions (Sevim et al., 2020). Also, CoVID-19 with cancer patients increase the higher risk of infections. Currently, there is no vaccine or specific treatment against CoVID-19 and drug research centres continuously investigating the potential drug against CoVID-19 (Osama and Amer, 2020). For the past 20 years two major coronavirus epidemics have occurred in public includes SARS-CoV approximately 8000 cases and 800 deaths and MERS-CoV 2,500 cases and 800 deaths and these continuing sporadically (Cascella et al., 2020).
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
  13. Fulltext Ivermectin: Potential Role as Repurposed Drug for COVID-19
    Dixit A, Yadav R, Singh AV
    Malays J Med Sci, 2020 Jul;27(4):154-158.
    PMID: 32863755 DOI: 10.21315/mjms2020.27.4.15
    Severe acute respiratory illness caused by 2019 novel coronavirus (2019-nCoV), officially named severe acute respiratory syndrome coronavirus (SARS-CoV-2) in late December 2019 is an extremely communicable disease. World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) as a pandemic as it has spread to at least 200 countries in a short span of time. Being a new disease there is lack of information about pathogenesis and proliferation pathways of this new coronavirus. Currently there is no effective treatment for coronavirus infection; major effort is to develop vaccine against the virus and development of therapeutic drugs for the disease. The development of genome-based vaccine and therapeutic antibodies require thorough testing for safety and will be available after some time. In the meanwhile, the available practical approach is to repurpose existing therapeutic agents, with proven safety record as a rapid response measure for the current pandemic. Here we discuss the presently used repurposed drugs for COVID-19 and the potential for ivermectin (IVM) to be used as a therapeutic option in COVID-19.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
  14. Fulltext Middle East respiratory syndrome coronavirus in the last two years: Health care workers still at risk
    Al-Tawfiq JA, Memish ZA
    Am J Infect Control, 2019 10;47(10):1167-1170.
    PMID: 31128983 DOI: 10.1016/j.ajic.2019.04.007
    BACKGROUND: An important emerging respiratory virus is the Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV had been associated with a high case fatality rate especially among severe cases.

    METHODS: This is a retrospective analysis of reported MERS-CoV cases between December 2016 and January 2019, as retrieved from the World Health Organization. The aim of this study is to examine the epidemiology of reported cases and quantify the percentage of health care workers (HCWs) among reported cases.

    RESULTS: There were 403 reported cases with a majority being men (n = 300; 74.4%). These cases were reported from Lebanon, Malaysia, Oman, Qatar, Saudi Arabia, and United Arab Emirates. HCWs represented 26% and comorbidities were reported among 71% of non-HCWs and 1.9% among HCWs (P < .0001). Camel exposure and camel milk ingestion were reported in 64% each, and the majority (97.8%) of those with camel exposures had camel milk ingestion. There were 58% primary cases and 42% were secondary cases. The case fatality rate was 16% among HCWs compared with 34% among other patients (P = .001). The mean age ± SD was 47.65 ± 16.28 for HCWs versus 54.23 ± 17.34 for non-HCWs (P = .001).

    CONCLUSIONS: MERS-CoV infection continues to have a high case fatality rate and a large proportion of patients were HCWs. Further understanding of the disease transmission and prevention mainly in health care settings are needed.

    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/pathogenicity*
  15. Fulltext Interferon Regulatory Factors IRF1 and IRF7 Directly Regulate Gene Expression in Bats in Response to Viral Infection
    Irving AT, Zhang Q, Kong PS, Luko K, Rozario P, Wen M, et al.
    Cell Rep, 2020 11 03;33(5):108345.
    PMID: 33147460 DOI: 10.1016/j.celrep.2020.108345
    Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/immunology
  16. Fulltext Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host
    Ahn M, Anderson DE, Zhang Q, Tan CW, Lim BL, Luko K, et al.
    Nat Microbiol, 2019 05;4(5):789-799.
    PMID: 30804542 DOI: 10.1038/s41564-019-0371-3
    Bats are special in their ability to host emerging viruses. As the only flying mammal, bats endure high metabolic rates yet exhibit elongated lifespans. It is currently unclear whether these unique features are interlinked. The important inflammasome sensor, NLR family pyrin domain containing 3 (NLRP3), has been linked to both viral-induced and age-related inflammation. Here, we report significantly dampened activation of the NLRP3 inflammasome in bat primary immune cells compared to human or mouse counterparts. Lower induction of apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and secretion of interleukin-1β in response to both 'sterile' stimuli and infection with multiple zoonotic viruses including influenza A virus (-single-stranded (ss) RNA), Melaka virus (PRV3M, double-stranded RNA) and Middle East respiratory syndrome coronavirus (+ssRNA) was observed. Importantly, this reduction of inflammation had no impact on the overall viral loads. We identified dampened transcriptional priming, a novel splice variant and an altered leucine-rich repeat domain of bat NLRP3 as the cause. Our results elucidate an important mechanism through which bats dampen inflammation with implications for longevity and unique viral reservoir status.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/genetics; Middle East Respiratory Syndrome Coronavirus/immunology
  17. Fulltext Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside
    Ayipo YO, Yahaya SN, Alananzeh WA, Babamale HF, Mordi MN
    Infect Genet Evol, 2021 Sep;93:104944.
    PMID: 34052418 DOI: 10.1016/j.meegid.2021.104944
    Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest. This review comprehensively highlights the common pathomechanisms and pharmacological targets of HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2, and potent therapeutic potentials from basic and clinical experimental investigations. The implicated targets for the prevention and treatment include the viral proteases (Mpro, PLpro, 3CLpro), viral structural proteins (S- and N-proteins), non-structural proteins (nsp 3, 8, 10, 14, 16), accessory protein (ns12.9), viroporins (3a, E, 8a), enzymes (RdRp, TMPRSS2, ADP-ribosyltransferase, MTase, 2'-O-MTase, TATase, furin, cathepsin, deamidated human triosephosphate isomerase), kinases (MAPK, ERK, PI3K, mTOR, AKT, Abl2), interleukin-6 receptor (IL-6R) and the human host receptor, ACE2. Notably among the 109 overviewed inhibitors include quercetin, eriodictyol, baicalin, luteolin, melatonin, resveratrol and berberine from natural products, GC373, NP164 and HR2P-M2 from peptides, 5F9, m336 and MERS-GD27 from specific human antibodies, imatinib, remdesivir, ivermectin, chloroquine, hydroxychloroquine, nafamostat, interferon-β and HCQ from repurposing libraries, some iron chelators and traditional medicines. This review represents a model for further translational studies for effective anti-CoV therapeutic designs.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/drug effects; Middle East Respiratory Syndrome Coronavirus/pathogenicity
  18. Fulltext Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen
    Nyon MP, Du L, Tseng CK, Seid CA, Pollet J, Naceanceno KS, et al.
    Vaccine, 2018 03 27;36(14):1853-1862.
    PMID: 29496347 DOI: 10.1016/j.vaccine.2018.02.065
    Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/immunology*
  19. Fulltext Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies
    Lim CC, Woo PCY, Lim TS
    Sci Rep, 2019 Apr 15;9(1):6088.
    PMID: 30988390 DOI: 10.1038/s41598-019-42628-6
    Antibody phage display has been pivotal in the quest to generate human monoclonal antibodies for biomedical and research applications. Target antigen preparation is a main bottleneck associated with the panning process. This includes production complexity, downstream purification, quality and yield. In many instances, purified antigens are preferred for panning but this may not be possible for certain difficult target antigens. Here, we describe an improved procedure of affinity selection against crude or non-purified antigen by saturation of non-binders with blocking agents to promote positive binder enrichment termed as Yin-Yang panning. A naïve human scFv library with kappa light chain repertoire with a library size of 109 was developed. The improved Yin-Yang biopanning process was able to enrich monoclonal antibodies specific to the MERS-CoV nucleoprotein. Three unique monoclonal antibodies were isolated in the process. The Yin-Yang biopanning method highlights the possibility of utilizing crude antigens for the isolation of monoclonal antibodies by phage display.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/immunology*
  20. Fulltext Novel coronavirus- A comprehensive review
    Nair AM, Shilpa PH, Shekhar V, Tiwari RVC, Shaik I, Dasari B, et al.
    J Family Med Prim Care, 2020 Jul;9(7):3200-3204.
    PMID: 33102270 DOI: 10.4103/jfmpc.jfmpc_496_20
    Recently coronavirus outbreak which started in Wuhan, China, has caused international concern that has affected more than 29 lakh people worldwide and with no vaccine or specific antiviral drugs present as well as oblivious testing of carriers who are generally asymptomatic, the use of general health intervention techniques are failing to comply. As compared to other epidemics like severe acute respiratory syndrome-coronavirus (SARS-CoV) and the Middle-East respiratory syndrome (MERS-CoV), coronavirus (also named as COVID-19) exhibit mild symptoms in the majority of cases. But in the case of a vulnerable population, it can prove to be life-threatening. Relying on proper barrier technique, use of chest computed tomography scans, managing co-morbid conditions of susceptible patients, identifying the pattern of disease spread as well as the use of polymerase chain reaction to assess the specificity of cases will eventually prove to be efficacious since most of the positive cases are asymptomatic at the beginning which poses a challenge to the primary health care physicians. The development of vaccines will also take some time so it is better to know about COVID-19 better and also follow quarantine restrictions properly till then. In this review, we try to put forward all the relevant studies which have been published by the end of March 2020 so as to summarize the natural history, diagnosis as well as treatment strategies for eradicating COVID-19, which will help in managing this pandemic.
    Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus
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