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  • 1
    In: mSystems, American Society for Microbiology, Vol. 6, No. 6 ( 2021-12-21)
    Abstract: After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid-2021, it remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus , a species closely related to SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus , which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease. IMPORTANCE The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.
    Type of Medium: Online Resource
    ISSN: 2379-5077
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2844333-0
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  • 2
    In: mSystems, American Society for Microbiology, Vol. 8, No. 2 ( 2023-04-27)
    Abstract: Over the past 150 years, vaccines have revolutionized the relationship between people and disease. During the COVID-19 pandemic, technologies such as mRNA vaccines have received attention due to their novelty and successes. However, more traditional vaccine development platforms have also yielded important tools in the worldwide fight against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety of approaches have been used to develop COVID-19 vaccines that are now authorized for use in countries around the world. In this review, we highlight strategies that focus on the viral capsid and outwards, rather than on the nucleic acids inside. These approaches fall into two broad categories: whole-virus vaccines and subunit vaccines. Whole-virus vaccines use the virus itself, in either an inactivated or an attenuated state. Subunit vaccines contain instead an isolated, immunogenic component of the virus. Here, we highlight vaccine candidates that apply these approaches against SARS-CoV-2 in different ways. In a companion article (H. M. Rando, R. Lordan, L. Kolla, E. Sell, et al., mSystems 8:e00928-22, 2023, https://doi.org/10.1128/mSystems.00928-22 ), we review the more recent and novel development of nucleic acid-based vaccine technologies. We further consider the role that these COVID-19 vaccine development programs have played in prophylaxis at the global scale. Well-established vaccine technologies have proved especially important to making vaccines accessible in low- and middle-income countries. Vaccine development programs that use established platforms have been undertaken in a much wider range of countries than those using nucleic acid-based technologies, which have been led by wealthy Western countries. Therefore, these vaccine platforms, though less novel from a biotechnological standpoint, have proven to be extremely important to the management of SARS-CoV-2. IMPORTANCE The development, production, and distribution of vaccines is imperative to saving lives, preventing illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Vaccines that use cutting-edge biotechnology have played an important role in mitigating the effects of SARS-CoV-2. However, more traditional methods of vaccine development that were refined throughout the 20th century have been especially critical to increasing vaccine access worldwide. Effective deployment is necessary to reducing the susceptibility of the world’s population, which is especially important in light of emerging variants. In this review, we discuss the safety, immunogenicity, and distribution of vaccines developed using established technologies. In a separate review, we describe the vaccines developed using nucleic acid-based vaccine platforms. From the current literature, it is clear that the well-established vaccine technologies are also highly effective against SARS-CoV-2 and are being used to address the challenges of COVID-19 globally, including in low- and middle-income countries. This worldwide approach is critical for reducing the devastating impact of SARS-CoV-2.
    Type of Medium: Online Resource
    ISSN: 2379-5077
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2844333-0
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  • 3
    In: mSystems, American Society for Microbiology, Vol. 8, No. 2 ( 2023-04-27)
    Abstract: In the 21st century, several emergent viruses have posed a global threat. Each pathogen has emphasized the value of rapid and scalable vaccine development programs. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made the importance of such efforts especially clear. New biotechnological advances in vaccinology allow for recent advances that provide only the nucleic acid building blocks of an antigen, eliminating many safety concerns. During the COVID-19 pandemic, these DNA and RNA vaccines have facilitated the development and deployment of vaccines at an unprecedented pace. This success was attributable at least in part to broader shifts in scientific research relative to prior epidemics: the genome of SARS-CoV-2 was available as early as January 2020, facilitating global efforts in the development of DNA and RNA vaccines within 2 weeks of the international community becoming aware of the new viral threat. Additionally, these technologies that were previously only theoretical are not only safe but also highly efficacious. Although historically a slow process, the rapid development of vaccines during the COVID-19 crisis reveals a major shift in vaccine technologies. Here, we provide historical context for the emergence of these paradigm-shifting vaccines. We describe several DNA and RNA vaccines in terms of their efficacy, safety, and approval status. We also discuss patterns in worldwide distribution. The advances made since early 2020 provide an exceptional illustration of how rapidly vaccine development technology has advanced in the last 2 decades in particular and suggest a new era in vaccines against emerging pathogens. IMPORTANCE The SARS-CoV-2 pandemic has caused untold damage globally, presenting unusual demands on but also unique opportunities for vaccine development. The development, production, and distribution of vaccines are imperative to saving lives, preventing severe illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Although vaccine technologies that provide the DNA or RNA sequence of an antigen had never previously been approved for use in humans, they have played a major role in the management of SARS-CoV-2. In this review, we discuss the history of these vaccines and how they have been applied to SARS-CoV-2. Additionally, given that the evolution of new SARS-CoV-2 variants continues to present a significant challenge in 2022, these vaccines remain an important and evolving tool in the biomedical response to the pandemic.
    Type of Medium: Online Resource
    ISSN: 2379-5077
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2844333-0
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  • 4
    In: mSystems, American Society for Microbiology, Vol. 7, No. 1 ( 2022-02-22)
    Type of Medium: Online Resource
    ISSN: 2379-5077
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
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  • 5
    In: mSystems, American Society for Microbiology, Vol. 6, No. 3 ( 2021-06-29)
    Abstract: Coronavirus disease 2019 (COVID-19) has caused global disruption and a significant loss of life. Existing treatments that can be repurposed as prophylactic and therapeutic agents may reduce the pandemic’s devastation. Emerging evidence of potential applications in other therapeutic contexts has led to the investigation of dietary supplements and nutraceuticals for COVID-19. Such products include vitamin C, vitamin D, omega 3 polyunsaturated fatty acids, probiotics, and zinc, all of which are currently under clinical investigation. In this review, we critically appraise the evidence surrounding dietary supplements and nutraceuticals for the prophylaxis and treatment of COVID-19. Overall, further study is required before evidence-based recommendations can be formulated, but nutritional status plays a significant role in patient outcomes, and these products may help alleviate deficiencies. For example, evidence indicates that vitamin D deficiency may be associated with a greater incidence of infection and severity of COVID-19, suggesting that vitamin D supplementation may hold prophylactic or therapeutic value. A growing number of scientific organizations are now considering recommending vitamin D supplementation to those at high risk of COVID-19. Because research in vitamin D and other nutraceuticals and supplements is preliminary, here we evaluate the extent to which these nutraceutical and dietary supplements hold potential in the COVID-19 crisis. IMPORTANCE Sales of dietary supplements and nutraceuticals have increased during the pandemic due to their perceived “immune-boosting” effects. However, little is known about the efficacy of these dietary supplements and nutraceuticals against the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) or the disease that it causes, CoV disease 2019 (COVID-19). This review provides a critical overview of the potential prophylactic and therapeutic value of various dietary supplements and nutraceuticals from the evidence available to date. These include vitamin C, vitamin D, and zinc, which are often perceived by the public as treating respiratory infections or supporting immune health. Consumers need to be aware of misinformation and false promises surrounding some supplements, which may be subject to limited regulation by authorities. However, considerably more research is required to determine whether dietary supplements and nutraceuticals exhibit prophylactic and therapeutic value against SARS-CoV-2 infection and COVID-19. This review provides perspective on which nutraceuticals and supplements are involved in biological processes that are relevant to recovery from or prevention of COVID-19.
    Type of Medium: Online Resource
    ISSN: 2379-5077
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
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  • 6
    In: mSystems, American Society for Microbiology, Vol. 6, No. 5 ( 2021-10-26)
    Abstract: The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus’s structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system’s protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).
    Type of Medium: Online Resource
    ISSN: 2379-5077
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2844333-0
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  • 7
    In: Journal of Virology, American Society for Microbiology, Vol. 82, No. 10 ( 2008-05-15), p. 5079-5083
    Abstract: The replicative properties of influenza virus hemagglutinin (HA) mutants with altered receptor binding characteristics were analyzed following intranasal inoculation of mice. Among the mutants examined was a virus containing a Y98F substitution at a conserved position in the receptor binding site that leads to a 20-fold reduction in binding. This mutant can replicate as well as wild-type (WT) virus in MDCK cells and in embryonated chicken eggs but is highly attenuated in mice, exhibiting titers in lungs more than 1,000-fold lower than those of the WT. The capacity of the Y98F mutant to induce antibody responses and the structural locations of HA reversion mutations are examined.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2008
    detail.hit.zdb_id: 1495529-5
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  • 8
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 189, No. 9 ( 2007-05), p. 3680-3681
    Abstract: Bacillus thuringiensis is an insect pathogen that is widely used as a biopesticide (E. Schnepf, N. Crickmore, J. Van Rie, D. Lereclus, J. Baum, J. Feitelson, D. R. Zeigler, and D. H. Dean, Microbiol. Mol. Biol. Rev. 62: 775-806, 1998). Here we report the finished, annotated genome sequence of B. thuringiensis Al Hakam, which was collected in Iraq by the United Nations Special Commission (L. Radnedge, P. Agron, K. Hill, P. Jackson, L. Ticknor, P. Keim, and G. Andersen, Appl. Environ. Microbiol. 69: 2755-2764, 2003).
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2007
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 9
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 188, No. 9 ( 2006-05), p. 3382-3390
    Abstract: Bacillus anthracis , Bacillus cereus , and Bacillus thuringiensis are closely related gram-positive, spore-forming bacteria of the B. cereus sensu lato group. While independently derived strains of B. anthracis reveal conspicuous sequence homogeneity, environmental isolates of B. cereus and B. thuringiensis exhibit extensive genetic diversity. Here we report the sequencing and comparative analysis of the genomes of two members of the B. cereus group, B. thuringiensis 97-27 subsp. konkukian serotype H34, isolated from a necrotic human wound, and B. cereus E33L, which was isolated from a swab of a zebra carcass in Namibia. These two strains, when analyzed by amplified fragment length polymorphism within a collection of over 300 of B. cereus , B. thuringiensis , and B. anthracis isolates, appear closely related to B. anthracis . The B. cereus E33L isolate appears to be the nearest relative to B. anthracis identified thus far. Whole-genome sequencing of B. thuringiensis 97-27and B. cereus E33L was undertaken to identify shared and unique genes among these isolates in comparison to the genomes of pathogenic strains B. anthracis Ames and B. cereus G9241 and nonpathogenic strains B. cereus ATCC 10987 and B. cereus ATCC 14579. Comparison of these genomes revealed differences in terms of virulence, metabolic competence, structural components, and regulatory mechanisms.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2006
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 10
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 59, No. 12 ( 2021-11-18)
    Abstract: The Burkholderia cepacia complex (BCC) is known for causing serious lung infections in people with cystic fibrosis (CF). These infections can require lung transplantation, eligibility for which may be guided by antimicrobial susceptibility testing (AST). While the Clinical and Laboratory Standards Institute recommends AST for BCC, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) does not, due to poor method performance and correlation with clinical outcomes. Furthermore, limited data exist on the performance of automated AST methods for BCC. To address these issues, reproducibility and accuracy were evaluated for disk diffusion (DD), broth microdilution (BMD), and MicroScan WalkAway using 50 B. cenocepacia and 50 B. multivorans isolates collected from people with CF. The following drugs were evaluated in triplicate: chloramphenicol (CAM), ceftazidime (CAZ), meropenem (MEM), trimethoprim-sulfamethoxazole (TMP-SMX), minocycline (MIN), levofloxacin (LVX), ciprofloxacin (CIP), and piperacillin-tazobactam (PIP-TAZ). BMD reproducibility was ≥ 95% for MEM and MIN only, and MicroScan WalkAway reproducibility was similar to BMD. DD reproducibility was  〈  90% for all drugs tested when a 3 mm cut-off was applied. When comparing the accuracy of DD to BMD, only MEM met all acceptance criteria. TMP-SMX and LVX had high minor errors, CAZ had unacceptable very major errors (VME), and MIN, PIP-TAZ, and CIP had both unacceptable minor errors and VMEs. For MicroScan WalkAway, no drugs met acceptance criteria. Analyses also showed that errors were not attributed to one species. In general, our data agree with EUCAST recommendations.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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