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      Nanoemulsions: the rising star of antiviral therapeutics and nano-delivery system - current status and prospects

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          Abstract

          Nanoemulsions (NEs) of essential oil (EO) have significant potential to target microorganisms, especially viruses. They act as a vehicle for delivering antiviral drugs and vaccines. Narrowing of drug discovery pipeline and the emergence of new viral diseases, especially, COVID-19 have created a niche to use nanoemulsions (NEs) for augmenting currently available therapeutic options. Published literature demonstrated that EOs have an inherent broad spectrum of activity across bacterial, fungal, and viral pathogens. The emulsification process significantly improved the efficacy of the active ingredients in the EOs. This article highlights the research findings and patent developments in the last two years especially, in EO antiviral activity, antiviral drug delivery, vaccine delivery, viral resistance development, and repurposing EO compounds against SARS-CoV2.

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          An interactive web-based dashboard to track COVID-19 in real time

          In December, 2019, a local outbreak of pneumonia of initially unknown cause was detected in Wuhan (Hubei, China), and was quickly determined to be caused by a novel coronavirus, 1 namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak has since spread to every province of mainland China as well as 27 other countries and regions, with more than 70 000 confirmed cases as of Feb 17, 2020. 2 In response to this ongoing public health emergency, we developed an online interactive dashboard, hosted by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA, to visualise and track reported cases of coronavirus disease 2019 (COVID-19) in real time. The dashboard, first shared publicly on Jan 22, illustrates the location and number of confirmed COVID-19 cases, deaths, and recoveries for all affected countries. It was developed to provide researchers, public health authorities, and the general public with a user-friendly tool to track the outbreak as it unfolds. All data collected and displayed are made freely available, initially through Google Sheets and now through a GitHub repository, along with the feature layers of the dashboard, which are now included in the Esri Living Atlas. The dashboard reports cases at the province level in China; at the city level in the USA, Australia, and Canada; and at the country level otherwise. During Jan 22–31, all data collection and processing were done manually, and updates were typically done twice a day, morning and night (US Eastern Time). As the outbreak evolved, the manual reporting process became unsustainable; therefore, on Feb 1, we adopted a semi-automated living data stream strategy. Our primary data source is DXY, an online platform run by members of the Chinese medical community, which aggregates local media and government reports to provide cumulative totals of COVID-19 cases in near real time at the province level in China and at the country level otherwise. Every 15 min, the cumulative case counts are updated from DXY for all provinces in China and for other affected countries and regions. For countries and regions outside mainland China (including Hong Kong, Macau, and Taiwan), we found DXY cumulative case counts to frequently lag behind other sources; we therefore manually update these case numbers throughout the day when new cases are identified. To identify new cases, we monitor various Twitter feeds, online news services, and direct communication sent through the dashboard. Before manually updating the dashboard, we confirm the case numbers with regional and local health departments, including the respective centres for disease control and prevention (CDC) of China, Taiwan, and Europe, the Hong Kong Department of Health, the Macau Government, and WHO, as well as city-level and state-level health authorities. For city-level case reports in the USA, Australia, and Canada, which we began reporting on Feb 1, we rely on the US CDC, the government of Canada, the Australian Government Department of Health, and various state or territory health authorities. All manual updates (for countries and regions outside mainland China) are coordinated by a team at Johns Hopkins University. The case data reported on the dashboard aligns with the daily Chinese CDC 3 and WHO situation reports 2 for within and outside of mainland China, respectively (figure ). Furthermore, the dashboard is particularly effective at capturing the timing of the first reported case of COVID-19 in new countries or regions (appendix). With the exception of Australia, Hong Kong, and Italy, the CSSE at Johns Hopkins University has reported newly infected countries ahead of WHO, with Hong Kong and Italy reported within hours of the corresponding WHO situation report. Figure Comparison of COVID-19 case reporting from different sources Daily cumulative case numbers (starting Jan 22, 2020) reported by the Johns Hopkins University Center for Systems Science and Engineering (CSSE), WHO situation reports, and the Chinese Center for Disease Control and Prevention (Chinese CDC) for within (A) and outside (B) mainland China. Given the popularity and impact of the dashboard to date, we plan to continue hosting and managing the tool throughout the entirety of the COVID-19 outbreak and to build out its capabilities to establish a standing tool to monitor and report on future outbreaks. We believe our efforts are crucial to help inform modelling efforts and control measures during the earliest stages of the outbreak.
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            Is Open Access

            Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

            How SARS-CoV-2 binds to human cells Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Yan et al. present the structure of human ACE2 in complex with a membrane protein that it chaperones, B0AT1. In the context of this complex, ACE2 is a dimer. A further structure shows how the receptor binding domain of SARS-CoV-2 interacts with ACE2 and suggests that it is possible that two trimeric spike proteins bind to an ACE2 dimer. The structures provide a basis for the development of therapeutics targeting this crucial interaction. Science, this issue p. 1444
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              Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle

              Since December 2019, a total of 41 cases of pneumonia of unknown etiology have been confirmed in Wuhan city, Hubei Province, China. Wuhan city is a major transportation hub with a population of more than 11 million people. Most of the patients visited a local fish and wild animal market last month. At a national press conference held today, Dr Jianguo Xu, an academician of the Chinese Academy of Engineering, who led a scientific team announced that a new‐type coronavirus, tentatively named by World Health Organization as the 2019‐new coronavirus (2019‐nCoV), had caused this outbreak. 1 The 2019‐nCoV has a different coronavirus‐specific nucleic acid sequence from known human coronavirus species, which are similar to some of the beta coronaviruses identified in bats. 2 , 3 The virus‐specific nucleic acid sequences were detected in lung fluid, blood and throat swab samples in 15 patients and the virus that was isolated showed a typical coronavirus appearance under electron microscopy. Further research will be conducted to better understand the new coronavirus to develop antiviral agents and vaccines. 4 We applauded the excellent job that has been done so far. The infection was first described in December. Within 9 days, a special team consisted of physicians, scientists and epidemiologists who ruled out several extremely contagious pathogens including SARS, which killed hundreds of people more than a decade ago, and MERS. This has surely alleviated environmental concerns as Hong Kong authorities had quickly stepped up the disinfection of trains and airplanes and checks of passengers due to this outbreak. Most of the patients visited the fish and wild animal market last month in Wuhan. This fish and wild animal market also sold live animals such as poultry, bats, marmots, and snakes. All patients received prompt supportive treatment in quarantine. Among them, seven patients were in serious condition and one patient died. All of the 42 patients so far confirmed were from China except one Thailand patient who was a traveler from Wuhan. Eight patients have been cured of the disease and were discharged from the hospital last week. The 2019‐nCoV now have been isolated from multiple patients and appears to be the culprit. But the mystery has not been completely solved yet. Until there is a formal published scientific manuscript, the facts can be argued, particularly regarding causality despite these facts having been officially announced. The data collected so far is not enough to confirm the causal relationship between the new‐type coronavirus and the respiratory disease based on classical Koch's postulates or modified ones as suggested by Fredricks and Relman. 5 The viral‐specific nucleic acids were only discovered in 15 patients, and successful virus culture was extremely limited to only a few patients. There remains considerable work to be done to differentiate between colonization, shedding, and infection. Additional strains of the 2019‐nCoV need to be isolated to study their homologies. It is expected that antigens and monoclonal antibodies will be developed so serology can be used to confirm previous and acute infection status. The episode demonstrates further the need for rapid and accurate detection and identification methods that can be used in the local hospitals and clinics bearing the burden of identifying and treating patients. Recently, the Clinical Laboratory Improvement Amendments (CLIA) of 1988 has waived highly sensitive and specific molecular devices known as CLIA‐waived devices so that these devices are gradually becoming available for point of care testing. Finally, the epidemiological similarity between this outbreak and that of SARS in 2002‐2003 6 is striking. SARS was then traced to animal markets 7 and eventually to palm civets. 8 Later bats were identified as animal reservoirs. 9 Could this novel coronavirus be originated from wild animals? The family Coronaviridae includes two subfamilies. 10 One, the subfamily Coronavirinae, contains a substantial number of pathogens of mammals that individually cause a remarkable variety of diseases, including pneumonia. In humans, coronaviruses are among the spectrum of viruses that cause the common cold as well as more severe respiratory disease—specifically SARS and MERS, which are both zoonoses. The second subfamily, Torovirinae, contains pathogens of both terrestrial and aquatic animals. The genus Torovirus includes the type species, equine torovirus (Berne virus), which was first isolated from a horse with diarrhea, and the Breda virus, which was first isolated from neonatal calves with diarrhea. White bream virus from fish is the type species of the genus Bafinivirus. However, there is no evidence so far that the seafood from the fish and animal market caused 2019‐nCoV‐associated pneumonia. This epidemiologic similarity clearly provides a starting point for the further investigation of this outbreak. In the meantime, this fish and animal market has been closed until the epidemiological work determines the animal host of this novel coronavirus. Only then will the miracle be complete.
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                Author and article information

                Journal
                Curr Opin Colloid Interface Sci
                Curr Opin Colloid Interface Sci
                Current Opinion in Colloid & Interface Science
                Elsevier Ltd.
                1359-0294
                1359-0294
                30 March 2021
                30 March 2021
                : 101458
                Affiliations
                [1]Centre for Nanobiotechnology, VIT University, Vellore-632014, Tamil Nadu, India
                Author notes
                []Corresponding author. Senior Professor Centre for Nanobiotechnology VIT University, Vellore-632014, India. Tel.: +91 416 2202624.
                [1]

                Equal contribution.

                Article
                S1359-0294(21)00042-X 101458
                10.1016/j.cocis.2021.101458
                8007535
                33814954
                c0d90dd9-d19f-4657-8845-d8e47b54c1d7
                © 2021 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 30 January 2021
                : 16 March 2021
                : 23 March 2021
                Categories
                Article

                microemulsion,nanoemulsion,antiviral activity,drug-delivery,vaccine delivery,drug resistance,drug repurposing

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