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2.
Viruses ; 14(2)2022 01 25.
Article in English | MEDLINE | ID: covidwho-1667339

ABSTRACT

In 2014 and 2021, two nucleic-acid vaccine candidates named MAV E2 and VGX-3100 completed phase III clinical trials in Mexico and U.S., respectively, for patients with human papillomavirus (HPV)-related, high-grade squamous intraepithelial lesions (HSIL). These well-tolerated but still unlicensed vaccines encode distinct HPV antigens (E2 versus E6+E7) to elicit cell-mediated immune responses; their clinical efficacy, as measured by HSIL regression or cure, was modest when compared with placebo or surgery (conization), but both proved highly effective in clearing HPV infection, which should help further optimize strategies for enhancing vaccine immunogenicity, toward an ultimate goal of preventing malignancies in millions of patients who are living with persistent, oncogenic HPV infection but are not expected to benefit from current, prophylactic vaccines. The major roadblocks to a highly efficacious and practical product remain challenging and can be classified into five categories: (i) getting the vaccines into the right cells for efficient expression and presentation of HPV antigens (fusion proteins or epitopes); (ii) having adequate coverage of oncogenic HPV types, beyond the current focus on HPV-16 and -18; (iii) directing immune protection to various epithelial niches, especially anogenital mucosa and upper aerodigestive tract where HPV-transformed cells wreak havoc; (iv) establishing the time window and vaccination regimen, including dosage, interval and even combination therapy, for achieving maximum efficacy; and (v) validating therapeutic efficacy in patients with poor prognosis because of advanced, recurrent or non-resectable malignancies. Overall, the room for improvements is still large enough that continuing efforts for research and development will very likely extend into the next decade.


Subject(s)
Cancer Vaccines/therapeutic use , Cervical Intraepithelial Neoplasia/therapy , Neoplasms/therapy , Papillomavirus Infections/therapy , Papillomavirus Vaccines/therapeutic use , Uterine Cervical Neoplasms/therapy , Vaccines, DNA/therapeutic use , Animals , Cervical Intraepithelial Neoplasia/immunology , Clinical Trials as Topic , Female , Humans , Immunogenicity, Vaccine , Neoplasms/immunology , Neoplasms/virology , Papillomavirus Infections/immunology , Papillomavirus Vaccines/immunology , Squamous Intraepithelial Lesions of the Cervix/therapy , Uterine Cervical Neoplasms/virology , Vaccines, DNA/immunology , /therapeutic use
3.
iScience ; 24(7): 102810, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1292758

ABSTRACT

Contrary to the fact that capillary action is ubiquitous in our daily lives, its role in drug delivery has not attracted attention. Therefore, its application in medicine and disease treatment has not been actively developed. This perspective begins by reviewing the principles, advantages, and limitations of the three existing drug delivery strategies: non-covalent interaction, cavity loading, and covalent conjugation. Then, we discussed the principle of capillary action in drug delivery and the influencing factors that determine its performance. To illustrate the advantages of capillary action over existing drug delivery strategies and how the capillary action could potentially address the shortcomings of the existing drug delivery strategies, we described five examples of using capillary action to design drug delivery platforms for disease treatment: marker pen for topical and transdermal drug delivery, microneedle patch with a sponge container for pulsatile drug delivery, core-shell scaffold for sustained release of growth factors, oral bolus for insulin delivery to the esophagus, and semi-hollow floating ball for intravesical and gastroprotective drug delivery. Each of the five drug delivery platforms exhibits certain unique functions that existing drug delivery technologies cannot easily achieve, hence expected to solve specific practical medical problems that are not satisfactorily resolved. As people pay more attention to capillary action and develop more drug delivery platforms, more unique functions and characteristics of capillary action in drug delivery will be explored. Thus, capillary action could become an important choice for drug delivery systems to improve therapeutic drug efficacy, treat diseases, and improve human health.

4.
Front Pharmacol ; 12: 671498, 2021.
Article in English | MEDLINE | ID: covidwho-1268277

ABSTRACT

SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.

5.
J Mater Chem B ; 9(35): 6988-6993, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1262017

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an RNA virus-based disease that can be deadly. For critically ill patients, mechanical ventilation is an important life-saving treatment. However, mechanical ventilation shows a trade-off between supporting respiratory function and ventilator-induced lung injury (VILI). Surfactant therapy is a medical administration of exogenous surfactant to supplement or replace deficient or dysfunctional endogenous surfactant. Surfactant therapy can be used to postpone or shorten the use of mechanical ventilation to minimize or avoid VILI, because surfactants can reduce surface tension, improve lung compliance, and enhance oxygenation. In addition, nanotechnology can be applied to improve the therapeutic effect and reduce the adverse effects of surfactants. In this perspective, we discussed how nanoparticles deliver surfactants through intravenous injection and inhalation to the expected lung disease regions where surfactants are mostly needed, and discussed the prospects of nanoparticle-mediated surfactant therapy in the treatment of patients with severe COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Carriers/chemistry , Nanoparticles/chemistry , Pulmonary Surfactants/therapeutic use , Administration, Inhalation , Animals , Drug Carriers/administration & dosage , Humans , Injections, Intravenous , Lung , Nanoparticles/administration & dosage , Pulmonary Surfactants/administration & dosage , Pulmonary Surfactants/chemistry , SARS-CoV-2
6.
Clin Chem ; 67(4): 672-683, 2021 03 31.
Article in English | MEDLINE | ID: covidwho-1165392

ABSTRACT

BACKGROUND: Infectious disease outbreaks such as the COVID-19 (coronavirus disease 2019) pandemic call for rapid response and complete screening of the suspected community population to identify potential carriers of pathogens. Central laboratories rely on time-consuming sample collection methods that are rarely available in resource-limited settings. METHODS: We present a highly automated and fully integrated mobile laboratory for fast deployment in response to infectious disease outbreaks. The mobile laboratory was equipped with a 6-axis robot arm for automated oropharyngeal swab specimen collection; virus in the collected specimen was inactivated rapidly using an infrared heating module. Nucleic acid extraction and nested isothermal amplification were performed by a "sample in, answer out" laboratory-on-a-chip system, and the result was automatically reported by the onboard information platform. Each module was evaluated using pseudovirus or clinical samples. RESULTS: The mobile laboratory was stand-alone and self-sustaining and capable of on-site specimen collection, inactivation, analysis, and reporting. The automated sampling robot arm achieved sampling efficiency comparable to manual collection. The collected samples were inactivated in as short as 12 min with efficiency comparable to a water bath without damage to nucleic acid integrity. The limit of detection of the integrated microfluidic nucleic acid analyzer reached 150 copies/mL within 45 min. Clinical evaluation of the onboard microfluidic nucleic acid analyzer demonstrated good consistency with reverse transcription quantitative PCR with a κ coefficient of 0.979. CONCLUSIONS: The mobile laboratory provides a promising solution for fast deployment of medical diagnostic resources at critical junctions of infectious disease outbreaks and facilitates local containment of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Laboratories , Mobile Health Units , Pathology, Molecular/methods , RNA, Viral/analysis , Adult , Automobiles , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing/instrumentation , Female , Humans , Lab-On-A-Chip Devices , Male , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Middle East Respiratory Syndrome Coronavirus/chemistry , Molecular Diagnostic Techniques/instrumentation , Molecular Diagnostic Techniques/methods , Pandemics , Pathology, Molecular/instrumentation , Robotics , SARS-CoV-2/chemistry
7.
Infect Dis Poverty ; 9(1): 163, 2020 Dec 02.
Article in English | MEDLINE | ID: covidwho-954569

ABSTRACT

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.


Subject(s)
COVID-19/pathology , COVID-19/virology , Influenza, Human/pathology , Influenza, Human/virology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Child , Child, Preschool , Comorbidity , Disease Progression , Female , Hospitalization , Humans , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza A Virus, H7N9 Subtype/pathogenicity , Influenza, Human/diagnosis , Influenza, Human/mortality , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Risk Factors , SARS-CoV-2/pathogenicity , Virus Shedding , Young Adult
8.
J Infect Dev Ctries ; 14(8): 847-852, 2020 08 31.
Article in English | MEDLINE | ID: covidwho-750608

ABSTRACT

INTRODUCTION: We analyzed the clinical characteristics of COVID-19 fecal/perianal swab nucleic acid-positive patients in our hospital and evaluated the effect of SARS-CoV-2 on the gastrointestinal tract. METHODOLOGY: Ninety-seven patients in the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 2, 2020 with fecal/perianal swab samples were selected as subjects and the results of real-time fluorescence reverse transcriptase-PCR SARS-CoV-2 nucleic acid detection of fecal/perianal swabs were used to divide subjects into positive and negative groups. RESULTS: Fecal/perianal swabs of 53.61% (52/97) patients were positive including 31 males (59.62%) and 21 females (40.38%). The negative group had more females than males (P = 0.001). The distribution of case classification based on the most severe condition observed after admission was different between groups: five (5.15%) critical type patients were all from the positive group (P = 0.029). There was no statistical difference in clinical manifestations between the groups. In the positive group, the mean nucleic acid-negative conversion time was 14.13 ± 8.61 days, which was significantly later than the negative group (6.98 ± 5.16 days; P < 0.001). In the positive group, 92% (48/52) had nucleic acid-negative conversion with a mean nucleic acid-negative conversion time of 22.58 ± 10.30 days. Among them, 41 (78.85%) cases were delayed compared with pharynx/nasal swab nucleic acid-negative conversion time. CONCLUSIONS: The positive rate of fecal/perianal swab nucleic acid in male patients was higher than that in female patients. Fecal/perianal swab nucleic acid positive may be an indicator of critical conditions in those with COVID-19.


Subject(s)
Anal Canal/virology , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Feces/virology , Pneumonia, Viral/virology , RNA, Viral/analysis , Adult , Aged , COVID-19 , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2
9.
Phytomedicine ; 85: 153311, 2021 May.
Article in English | MEDLINE | ID: covidwho-733664

ABSTRACT

BACKGROUND: Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge. METHODS: A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar). RESULTS: Through the screening for natural products with antiviral activities against different types of the human coronavirus, extracts of Lycoris radiata (L'Hér.), Gentiana scabra Bunge, Dioscorea batatas Decne., Cassia tora L., Taxillus chinensis (DC.), Cibotium barometz L. and Echinacea purpurea L. showed a promising effect against SARS-CoV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4`-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab. CONCLUSION: Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , SARS-CoV-2/drug effects , COVID-19 Vaccines , Clinical Trials as Topic , Drug Evaluation, Preclinical , Humans , Molecular Structure , Pandemics , Plant Preparations/pharmacology
10.
Int J Environ Res Public Health ; 17(16)2020 08 11.
Article in English | MEDLINE | ID: covidwho-705801

ABSTRACT

Lately, myriad of novel viruses have emerged causing epidemics such as SARS, MERS, and SARS-CoV-2, leading to high mortality rates worldwide. Thus, these viruses represented a challenging threat to mankind, especially considering the miniscule data available at our disposal regarding these novel viruses. The entire world established coordinative relations in research projects regarding drug and vaccine development on the external range, whereas on the internal range, all countries declared it an emergency case through imposing different restrictions related to their border control, large gatherings, school attendance, and most social activities. Pandemic combating plans prioritized all sectors including normal people, medical staff politicians, and scientists collectively shouldered the burden. Through planning and learning the previous lessons from SARS and MERS, healthcare systems could succeed in combating the viral spread and implications of these new pandemics. Different management strategies including social distance, social awareness and isolation represented successful ways to slow down the spread of the pandemic. Furthermore, pre-preparedness of some countries for emergencies is crucial to minimize the consequences of the crisis.


Subject(s)
Communicable Disease Control/organization & administration , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Betacoronavirus , COVID-19 , Disaster Planning/organization & administration , Global Health , Humans , SARS-CoV-2
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